Skripsi subkronik

8/18/2019 Skripsi subkronik

1/112

UJI TOKSISITAS SUBKRONIS SENYAWA

ASAM 2-(4-(KLOROMETIL)BENZOILOKSI)BENZOAT

TERHADAP LAMBUNG, GINJAL DAN HEPAR MENCIT

( Mus musculus)

YOSEPHIN MARIANY DEWI NEONBASU

24430003!

PROGRAM STUDI S

"AKULTAS "ARMASI

UNI#ERSITAS KATOLIK WIDYA MANDALA SURABAYA

20$

1


2/112

2


3/112

3


4/112

1


5/112

ABSTRAK

UJI TOKSISITAS SUBKRONIS SENYAWA

ASAM 2-(4-(KLOROMETIL)BENZOILOKSI)BENZOAT

TERHADAP LAMBUNG, GINJAL DAN HEPAR MENCIT

( Mus musculus)

Yosephin Mariany Dewi Neonbasu

2443010037

Senyawa asam 2-(4-(klorometilben!oiloksiben!oat merupakan hasil "ari

senyawa asam salisilat yan# "ireaksikan "en#an asam 4-

klorometilben!oilklori"a melalui reaksi asilasi$ Senyawa ini merupakan

mo"i%ikasi struktur turunan asam salisilat yan# "ibuat "en#an tu&uan untuk menin#katkan akti'itas anal#esik "an menurunkan e%ek sampin#$ enelitian ini

"ilakukan untuk meneliti toksisitas subkronis senyawa asam 2-(4-

(klorometilben!oiloksiben!oat pa"a lambun#) hepar "an #in&al men*it$

Meto"e pen#u&ian toksisitas subkronis ini men#a*u pa"a +,D 407) "imana

men*it Swiss webster &antan "iba#i men&a"i 3 kelompok) yaitu kelompok

kontrol yan# "iba#i "alam kelompok kontrol ne#ati% (./ 3) kontrol positi%

(asam asetilsalisilat 1)3 m#20 #) kontrol satelit kelompok u&i ( asam 2-(4-

(klorometilben!oiloksiben!oat "an kelompok satelit yan# masin#-masin#

terba#i "alam 3 kelompok "osis) yaitu 1)3 m#20 # 2) m#20 # "an 3)5m#20 #$ 6asil penelitian pa"a lambun# kelompok u&i menun&ukkan

ter&a"inya kerusakan lambun# yan# "itan"ai "en#an terlihatnya bintik-bintik

merah pa"a mukosa lambun# yan# &u#a mun*ul pa"a kelompok kontrol positi%$

6asil analisis &umlah nekrosis pa"a hepar menun&ukkan ter&a"inya penin#katan

&umlah nekrosis pa"a kelompok u&i "iban"in#kan "en#an kelompok kontrol

se"an#kan pa"a #in&al &umlah nekrosis kelompok kontrol positi% lebih tin##i

"iban"in#kan kelompok u&i$ 6asil analisa "ata pa"a kelompok satelit

menun&ukkan ter&a"inya penin#katan nekrosis pa"a hepar "an #in&al men*it$

Data hasil perhitun#an sel nekrosis pa"a hepar "an #in&al "ilakukan analisis

statistik "an menun&ukkan ti"ak a"anya perbe"aan bermakna antar kelompok (0)08$ Dari hasil analisa "apat "isimpulkan bahwa pemberian senyawa asam

2-(4-(klorometilben!oiloksiben!oat "apat menimbulkan e%ek nekrosis pa"a

hepar "an #in&al serta e%ek iritasi pa"a lambun# men*it Swiss webster &antan$

9ika "iban"in#kan "en#an asam asetilsalisilat) senyawa asam 2-(4-

(klorometilben!oiloksiben!oat menimbulkan e%ek nekrosis yan# lebih ren"ah

pa"a #in&al "an hepar serta e%ek iritasi pa"a lambun# men*it$

K%&% K'* : /sam asetilsalisilat) asam 2-(4-(klorometilben!oiloksiben!oat)

toksisitas subkronis) lambun#) hepar) #in&al

2


6/112

ABSTRACT

SUBCHRONIC TO+ICITY STUDY O"

2-(4- (CHLOROMETHYL)BENZOILO+Y)BENZOIC ACID IN THE

STOMACH, KIDNEY, AND LI#ER O" MICE ( Mus musculus)

Yosephin Mariany Dewi Neonbasu

2443010037

;he 2- (4- (*hloromethyl ben!oilo


7/112

KATA PENGANTAR

u&i syukur penulis pan&atkan kepa"a ;uhan Yesus >ristus karena

kasih karuniaNya) skripsi ini "apat terselesaikan$ Skripsi yan# ber&u"ul ?

U* T/**&% S'5/* S%.% A%6 2-(4-

(K7//6&*7)58/*7/*)58/%& &9%1%: L%65';, G*%7 1% H:%

M*& ( Mus musculus)? ini "ia&ukan seba#ai salah satu syarat untuk

memperoleh #elar Sar&ana @armasi "i Ani'ersitas >atolik =i"ya Man"ala

Surabaya$

enyusunan skripsi ini terselesaikan berkat bantuan "an ker&asama

"ari berba#ai pihak) baik "ari "alam maupun luar uni'ersitas$ +leh karena

itu) penulis menyampaikan banyak terima kasih kepa"a pihak-pihak yan#

telah membantu selama proses pembuatan skripsi ini :

1$ Drs$ >un*oro @oe) h$D$) .$Dip$S*$) /pt$ selaku Bektor

Ani'ersitas >atolik =i"ya Man"ala Surabaya) atas sarana "an

prasarana serta kesempatan yan# "iberikan untuk menempuh

pen"i"ikan "i @akultas @armasi Ani'ersitas >atolik =i"ya

Man"ala Surabaya$

2$ Martha ,r'ina) M$Si$) /pt$ selaku Dekan @akultas @armasi

Ani'ersitas >atolik =i"ya Man"ala yan# telah memberikan

%asilitas "an bantuan "alam penyusunan skripsi ini$

3$ =ahyu Dewi ;amayanti) M$S*$) /pt$ selaku pembimbin# C "an

atherine aroline) M$Si$) /pt$ selaku pembimbin# CC yan# telah

banyak memberikan saran "an nasehat serta meluan#kan waktu)

tena#a) pikiran "an kesabaran "alam membimbin#) men#arahkan

serta memberikan petun&uk "an moti'asi yan# san#at berhar#a "ari

awal hin##a akhir penyusunan skripsi ini$

4


8/112

4$ /n#eli*a >resnamurti) M$@arm$) /pt "an Dr$ Cwan Sahrial 6ami")

M$Si$) "rh$ selaku ;im en#u&i Skripsi) yan# telah banyak

memberikan masukan "an saran serta bimbin#an "alam menyusun

naskah skripsi$

8$ @ari"a anawati D$) M$S*$ selaku enasehat /ka"emik) atas

nasehat "an bimbin#annya "alam hal aka"emik$

$ Seluruh Dosen "an sta% en#a&ar @akultas @armasi Ani'ersitas

>atolik =i"ya Man"ala Surabaya yan# telah men"i"ik selama

menuntut ilmu Strata-1$

7$ aboran-laboran laboratorium yan# telah banyak membantu "alam

menyelesaikan penelitian ini) "iantaranya ak =awan) ak /nan#)

ak /ri) "an ak Ben"y$

E$ >epala laboratorium atolo#i /natomi .e"un# Diagnostic Center

BSAD Dr$ Soetomo Surabaya yan# telah membantu "alam

pembuatan preparat histolo#is yan# "i#unakan "alam penelitian

ini$

5$ +ran# tua ter*inta apak @ilo#onius Neonbasu "an Cbu Sri

Mulyani a"ik-a"ik tersayan# =iwin) u"i "an Merlin serta

seluruh keluar#a besar ter*inta yan# selalu men"oakan "an

memberikan "ukun#an moril maupun materil serta seman#at

selama kuliah hin##a "apat menyelesaikan skripsi ini$

10$ ;eman-teman seper&uan#an "alam penelitian ini) =ulan) Nan*y)

No'ita) @el"y) 6ans) yan# memberikan "ukun#an "alam

membantu proses penyusunan skripsi ini$

11$ =illy 6aumahu) i*in Seran) C'o 9inus) Da%rosa 9ik) Fi'in ;o"a

teman-teman D25) sahabat-sahabat) ,lis Nurak) Cren ae) >ristin

atu) Yolan ;uan) Yuan uan) Besty >risantis) utri @an"a) /%ly

ehan) Marline Nae) 9oi) erto) Bi*har") "an Fi*tor yan# telah

5


9/112

men&a"i tempat *urhat "an memberikan seman#at) moti'asi "an

bantuan "alam proses penyusunan skripsi ini$

12$ Seluruh teman-teman an#katan 2010 yan# ti"ak "apat "isebutkan

satu persatu) terima kasih atas kebersamaan) "ukun#an "an

seman#atnya selama penyusunan skripsi ini "an "alam menuntut

ilmu Strata-1 "i @akultas @armasi Ani'ersitas >atolik =i"ya

Man"ala Surabaya$

13$ Serta semua pihak yan# telah memberikan bantuan baik se*ara

lan#sun# maupun ti"ak lan#sun# yan# ti"ak "apat "isebutkan satu

persatu yan# telah membantu penyusunan skripsi ini$

/khir kata) san#at "isa"ari bahwa penulisan skripsi ini masih &auh

"ari kesempurnaan$ +leh karena itu) se#ala kritik "an saran yan#

memban#un san#at "iharapkan untuk penyempurnaan skripsi ini$ Skripsi ini

"ipersembahkan untuk almamater ter*inta Ani'ersitas >atolik =i"ya

Man"ala Surabaya) semo#a skripsi ini "apat memberikan sumban#an yan#

berman%aat ba#i masyarakat pa"a umumnya "an ba#i perkemban#an ilmu

ke%armasian pa"a khususnya$

Surabaya) 9uni 2018

enulis

6


10/112

DA"TAR ISI

6alaman

/S;B/> $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

i

ABSTRACT...................................................................

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

ii

>/;/ ,N./N;/B$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

iii

D/@;/B CSC $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

i'D/@;/B /MCB/N

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

i<

D/@;/B ;/,

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$<

D/@;/B ./M/B

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$


11/112

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

1

1$1 atar elakan#

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

1

1$2 Bumusan Masalah

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

8

1$3 ;u&uan enelitian

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

8

1$4 6ipotesis enelitian

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

8

1$8 Man%aat enelitian

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

CC$ TINJAUAN PUSTAKA

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

7

2$1$ /sam /setilsalisilat

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

7

8


12/112

2$2$ /sam 2-(4-(klorometilben!oiloksiben!oat$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

E

2$3$ A&i ;oksisitas

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

10

2$3$1$ ,'aluasi A&i ;oksisitas

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

11

2$4$ 6ewan oba Men*it ( Mus musculus

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

12

2$8$ +r#an

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

18

2$8$1$ ambun#

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

18

2$8$2$ 6epar $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ 1E

2$8$3$ .in&al $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ 28

2$ Statistik arametrik "an Nonparametrik

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

31

6alaman

9


13/112

CCC$ METODE PENELITIAN

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

33

3$1$ ahan) /lat "an 6ewan oba enelitian

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

33

3$1$1 ahan enelitian

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

33

3$1$2 /lat enelitian

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

33

3$1$3$ 6ewan oba

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

33

3$2$ A&i ;oksisitas Subkronis

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

34

3$3$ rose"ur A&i ;oksisitas Subkronis

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

34

3$3$1$ embuatan Se"iaan ./ 3

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

34

10


14/112

3$3$2$ embuatan Se"iaan A&i "an Se"iaan

emban"in#

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

38

3$3$3$ embuatan Dapar @ormalin

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

38

3$3$4$ emberian Se"iaan A&i "an Se"iaan

emban"in#

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

3

3$3$8$ ersiapan 6ewan oba

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

3

3$3$$ elaksanaan A&i ;oksisitas Subkronis

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

37

3$3$7$ embuatan reparat 6istolo#is ewarnaan 6,

( Hematoxylin ErlichEosin$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ 3E3$3$E$ en#amatan pa"a +r#an A&i

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

42

3$4$ Fariabel enelitian

11


15/112

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

43

3$8$ /nalisis Statistik

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

43

3$$ 6ipotesis Statistik

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

43

3$7$ emba#ian >elompok pa"a Men*it "alam en#u&ian

;oksisitas$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ 48

CF$ HASIL PENELITIAN DAN PEMBAHASAN

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$


16/112

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

80

4$2$ embahasan

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

84

4$2$3$ embahasan Makroskopis ambun#

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

84

4$2$3$ embahasan 6istopatolo#i 6epar

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

8

4$2$3$ embahasan Makroskopis .in&al

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

85

F$ SIMPULAN DAN SARAN

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

2

8$1$ Simpulan

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

2

8$2$ Saran

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

2

13


17/112

D/@;/B AS;/>/

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

3

/MCB/N

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

70

14


18/112

DA"TAR LAMPIRAN

ampiran 6alaman

1$ ./M/B/N N,>B+SCS 6,/B D/N .CN9/

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

70

$1$1 >aryolosis

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

70

$1$2 karyoreksis

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

70

$1$3 iknosis

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

71

2$ M,;+D, ,B6C;AN./N S, N,>B+SCS

72

3$ D/;/ ,B6C;AN./N 9AM/6 S, N,>B+SCS

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

73

4$ +/6/N D/;/

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

7

8$ ;/, @ A9C +N,-=/Y /N+F/

15


19/112

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

E

$ ./M/B/N MC>B+S>+CS S, N,>B+SCS S,$$$$$$$$$$$ E7

16


20/112

DA"TAR TABEL

;abel 6alaman

1$1 6asil penentuan ,D80

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

2

2$1 >elas potensi toksik akut senyawa pa"a hewan *oba

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

11

3$1 @ormula suspensi senyawa u&i "an pemban"in#

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

38

4$1 ;abel perban"in#an nilai &umlah sel nekrosis hepar

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

4E

4$2 ;abel hubun#an perban"in#an antar kelompok (;ukey

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

45

4$3 ;abel perban"in#an nilai rata-rata &umlah kerusakanhistolo#is #in&al pa"a masin#-masin# kelompok

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

82

4$4 ;abel hubun#an perban"in#an antar kelompok (;ukey

17


21/112

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

83

DA"TAR GAMBAR

.ambar 6alaman

1$1 Struktur turunan asam ben!oilsalisilat

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

3

2$1 Struktur asam asetilsalisilat

18


22/112

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

7

2$2 Struktur asam 2-(4-(klorometilben!oiloksiben!oat

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

E

2$3 Men*it

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

12

2$4 /natomi lambun#

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

18

2$8 >ea"aan lambun# men*it "en#an kon"isi normal "an tukak

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

1E

2$ /natomi hepar

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

15

2$7 obulus hepar$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

21

2$E Sinus hepar

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

21

19


23/112

2$5 6epatosit

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

22

2$10 ,mpe"u kanalikuli$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ 22

2$11 6istolo#i hepar men*it

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

23

2$12 /natomi #in&al

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

2

2$13 ;ubulus #in&al

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

2E

2$14 .lomerulus #in&al

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

2E

2$18 >erusakan #in&al men*it

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

31

3$1 emba#ian kelompok pa"a men*it

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

48

4$1 enampan# makroskopis or#an lambun# men*it

20


24/112

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

4

4$2 Dia#ram batan# perban"in#an tin#kat keparahan nekrosis

or#an hepar pa"a masin#-masin# kelompok

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

47

4$3 6istopatolo#i hepar men*it yan# men#alami nekrosis

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

80

4$4 Dia#ram batan# perban"in#an tin#kat keparahan nekrosis

sel epitel or#an #in&al masin#-masin# kelompok

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

81

4$8 6istopatolo#i #in&al men*it yan# men#alami nekrosis

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$

84

21


25/112

BAB I

PENDAHULUAN


26/112

"arah "apat menyebabkan nyeri) "emam "an in%lamasi (@orsythe) 1551$

/sam asetilsalisilat mempunyai nilai D80 oral sebesar 280 m#># pa"a

hewan tikus (.o"oy) 2013$

/sam asetilsalisilat merupakan #olon#an obat !on Steroi"al Anti

#n$lammatory Drugs (NS/CDs) "imana obat ini memiliki stabilitas yan#

ren"ah sehin##a mu"ah terurai men&a"i asam salisilat "an asam asetat$

Stabilitas suatu obat san#at berpen#aruh karena untuk men#etahui kualitas

suatu obat serta ketahanannya terha"ap %aktor-%aktor tertentu seperti suhu

"an *ahaya$ Antuk menin#katkan akti'itas anal#esik "an menurunkan e%ek

sampin#) maka perlu "ilakukan mo"i%ikasi struktur turunan asam salisilat

"en#an *ara men#ubah #u#us karboksil melalui pembentukan #aram) ester

atau ami"a substitusi pa"a #u#us hi"roksil mo"i%ikasi pa"a #u#us

karboksil "an hi"roksil memasukkan #u#us hi"roksil atau #u#us yan# lain

pa"a *in*in aromatik atau men#ubah #u#us-#u#us %un#sional (Siswan"ono

"an Soekar"&o) 2000$

;abel 1$1$ 6asil penentuan ,D80 senyawa "en#an #u#us B serta "ata si%at lipo%ilik (G),

elektronik (Hm) H p) Hmp "an sterik (,s "ari atom atau #u#us B (Soekar"&o "kk$) 2005

N/ G';'(R ) = > E ED$0 L/;

?ED$0

@6 @: @6:

1 3-62l 0$17 0$11 0 0$11 -0$24 $

2 4-62l 0$17 0 0$20 0$20 -0$24 -1$27E53 4-+@3 1$04 0 0$38 0$38 0 22$2 -1$3848

4 2-l 0$71 0 0 0 0$27 40$31 -1$084

8 4-(633 1$5E 0 -0$20 -0$20 -1$84 2$8 -1$4287

3)8-l2 1$42 1$8 0 1$8 0$84 28$32 -1$40387 4-465 2$24 -0$1 0 -0$1 -0$35 8E -1$734

E 6 0 0 0 0 1$24 32 -1$8081

5 4-N+2 -0$2E 0 0$7E 0$7E -1$2E 43 -1$33810 4-+63 -0$02 0 -0$27 -0$27 0$5 23 -1$317

11 4-63 0$8 0 -0$17 -0$17 0 22 -1$3424

12 3-l 0$71 0$37 0 0$37 0$27 20


27/112

Si%at-si%at lipo%ilik (G)) elektronik (H "an sterik (,s "ari #u#us

terha"ap si%at senyawa in"uk "apat mempen#aruhi akti'itas biolo#is$ Dosis

e%ekti% 80 (,D80 a"alah "osis suatu obat yan# "apat berpen#aruh terha"ap

80 "ari &umlah hewan yan# "iu&i$

eberapa penelitian telah "ilakukan sebelumnya untuk men#hasilkan

turunan ben!oilsalisilat yan# *ukup potensial apabila "i#unakan seba#ai

obat anal#etik$ Soekar"&o "kk$ (2005) telah melakukan penelitian "an

penentuan hubun#an kuantitati% struktur turunan ben!oilsalisilat "en#an

akti'itas anal#esik pa"a men*it$ 6asil penelitian yan# telah "ilakukan

sebelumnya "en#an senyawa peman"u asam ben!oilsalisilat "apat

"itun&ukkan pa"a .ambar 1$1$

O

COOH

C

O

R

.ambar 1$1$ Struktur yan# men##ambarkan turunan asam ben!oilsalisilat) "imana B a"alah#u#us yan# "imo"i%ikasi

(Soekar"&o "kk$) 2005

Dari hasil penelitian Soekar"&o "kk$ (2005) "iketahui bahwa asam 2-

(4-(klorometilben!oiloksiben!oat a"alah salah satu turunan senyawa

ben!oiloksi ben!oat yan# memiliki akti'itas anal#esik yan# lebih besar

"iban"in#kan "en#an turunan yan# lain yaitu "en#an "osis yaitu 15

m#># su"ah "apat menun&ukkan akti'itas anal#esik yan# besar$ /sam

2-(4-(klorometilben!oiloksiben!oat merupakan hasil "ari senyawa asam

salisilat yan# "ireaksikan "en#an asam 4-klorometilben!oil klori"a melalui

3


28/112

reaksi asilasi$ Antuk men#etahui toksisitas senyawa tersebut) Soekar"&o

"kk$ (2011 melakukan u&i toksisitas akut terha"ap men*it$ 6asil penelitian

menun&ukkan bahwa senyawa asam 2-(4-(klorometilben!oiloksiben!oat

memiliki nilai D80 2000 m#># (Soekar"&o "kk$) 2011 serta hasil har#a

,D80 senyawa asam 2-(4-(klorometilben!oiloksiben!oat sebesar 11)31

m#>#) se"an#kan har#a ,D80 senyawa asam asetilsalisilat sebesar

20)E3 m#># (Baniya) 2005$ 6al tersebut menun&ukkan bahwa akti'itas

anal#esik senyawa asam 2-(4-(klorometilben!oiloksiben!oat lebih tin##i

"aripa"a akti'itas anal#esik senyawa asam asetilsalisilat$ Antuk "apat

men#arah pa"a obat anal#etik yan# baru "an aman "i#unakan namun ti"ak

toksik) maka "ilakukan penelitian ke tahap selan&utnya yaitu u&i toksisitas

subkronis$

enelitian sebelumnya) =i"harna "kk$ (2014 telah melakukan u&i

toksisitas akut pa"a turunan asam ben!oilsalisilat yan# menun&ukan a"anya

kematian seekor men*it betina pa"a hari ke 2 setelah pemberian senyawa

asam +-(3-kloroben!oilsalisilat "en#an "osis 2000 m#>#$ 6al ini

ter&a"i karena a"anya kerusakan pa"a or#an lambun#$ Selan&utnya

"ilakukan penelitian u&i toksisitas subkronis pa"a men*it &antan "an betina

men##unakan parameter analisis hematolo#i$ Antuk melan&utkan penelitian

u&i toksisitas akut sebelumnya) akan "ilakukan u&i toksisitas subkronis

terha"ap or#an hati) lambun#) "an #in&al men*it yan# su"ah "iambil

sebelumnya untuk melihat apakah ter&a"i toksisitas pa"a or#an-or#an

tersebut$


29/112

toksik terha"ap hepar "an #in&al men*it serta ba#aimana

perban"in#annya "en#an asam asetilsalisilatI

1$2$2 /pakah pemberian senyawa asam 2-(4-

(klorometilben!oiloksiben!oat "apat menimbulkan e%ek

iritasi terha"ap lambun# men*it serta ba#aimana

perban"in#annya "en#an asam asetilsalisilatI


30/112


31/112

BAB II

TINJAUAN PUSTAKA

2


32/112

"ihi"rolisa) setelah itu "i"istribusikan ke seluruh tubuh "an "en#an se#era

menyebar ke seluruh tubuh "an *airan transeluler setelah "iabsorbsi$

>e*epatan absorbsi ter#antun# "ari ke*epatan "isinte#rasi "an "isolusi

tablet) p6 permukaan mukosa "an waktu pen#oson#an lambun#$ Salisilat

"apat "itemukan "alam *airan sino'ial) *airan spinal) liur "an air susu$

>a"ar tertin##i "i*apai kira-kira 2 &am setelah pemberian (=imana) 1558$

Se"iaan obat NS/CDs memiliki akti'itas pen#hambat ra"an# "en#an

mekanisme ker&a men#hambat biosintesis prosta#lan"in "ari asam

arakhi"onat melalui pen#hambatan akti'itas en!im siklooksi#enase (Na"i)

1552$ erbe"a "en#an NS/CDs lainnya) asam asetilsalisilat merupakan

inhibitor irre'ersibel siklooksi#enase (+J (>artasasmita) 2002$

2


33/112

melalui penentuan titik leleh) "i"apatkan hasil berkisar antara 187-185K

(Martak "kk$) 2005$

/kti'itas biolo#is suatu senyawa "apat "ipen#aruhi oleh si%at %isiko-

kimia salah satunya si%at lipo%ilik$ enin#katan si%at lipo%ilitas suatu

senyawa "apat menin#katkan penembusan senyawa "alam membran$ Si%at

lipo%ilik suatu senyawa "apat "itun&ukkan "en#an har#a lo# $ Senyawa

asam 2-(4-(klorometilben!oiloksiben!oat mempunyai har#a lo# L 3)73)

se"an#kan senyawa asam asetilsalisilat mempunyai har#a lo# L 1)21$ +leh

karena itu "apat "isimpulkan bahwa senyawa asam 2-(4-

(klorometilben!oiloksiben!oat mempunyai si%at lipo%ilik yan# besar

"iban"in#kan "en#an asam asetilsalisilat) penin#katan lipo%ilitas "ari

senyawa asam 2-(4-(klorometilben!oiloksiben!oat "isebabkan oleh

penambahan #u#us 4-klorometilben!oil klori"a (Martak "kk$) 2005$

6ar#a %aktor retar"asi hasil u&i kromato#ra%i lapis tipis (>; asam

2-(4-klorometilben!oiloksiben!oat "alam %ase #erak n-heksana : etanol

(1:2 a"alah 0)75 se"an#kan "alam %ase #erak kloro%orm : etanol (4:1

a"alah 0)52 "an "alam %ase #erak etil asetat : etanol (2:1 a"alah 0)50

(Botua) 2014$

6asil penelitian yan# "ilakukan oleh =i"harna "kk$ (2014

menun&ukkan bahwa senyawa asam 2-(4-(klorometilben!oiloksiben!oat

memiliki e%ek toksisitas subkronis yan# sama bila "iban"in#kan "en#an

senyawa asam asetilsalisilat$ enelitian yan# "ilakukan ber"asarkan pro%il

"arah "an urin pa"a men*it menu&ukkan bahwa pa"a parameter urin

"i"apatkan hasil ti"ak a"a perbe"aan bermakna antara toksisitas subkronis

senyawa asam 2-(4-(klorometilben!oiloksiben!oat "en#an senyawa asam

asetilsalisilat se"an#kan pa"a parameter pro%il "arah) "i"apatkan "ata

a"anya perbe"aan bermakna hematokrit) sel "arah merah) hemo#lobin pa"a

kelompok men*it &antan "an hematokrit) hemo#lobin pa"a men*it betina

9


34/112

antara asam asetilsalisilat "en#an senyawa asam 2-(4-

(klorometilben!oiloksiben!oat$

2


35/112

b$ A&i toksisitas subkronis

A&i toksisitas subkronis "ilakukan untuk men#e'aluasi e%ek

senyawa) apabila "iberikan kepa"a hewan u&i se*ara berulan#-ulan#$ A&i

toksisitas subkronis menyan#kut e'aluasi seluruh hewan untuk men#etahui

e%ek patolo#i "an e%ek histolo#i$ A&i ini "apat men#hasilkan in%ormasi

toksisitas !at u&i yan# berkaitan "en#an or#an sasaran) e%ek pa"a or#an itu)

"an hubun#an "osis e%ek "an "osis respons$

*$ A&i toksisitas kronis

a"a u&i toksisitas kronis ini "ilakukan e'aluasi patolo#i len#kap$

A&i toksisitas kronis "ilakukan "en#an memberikan senyawa u&i berulan#-

ulan# selama masa hi"up hewan u&i atau seba#ian besar masa hi"upnya)

misalnya 1E bulan untuk men*it) 24 bulan untuk tikus) "an 7-10 tahun untuk

an&in# "an monyet (u) 1558 >ar"inin#sih) 2002 6armita "an Ba"&i)

2008$ en#u&ian toksisitas kronis khusus "apat meliputi u&i terato#enik)

muta#enik "an karsino#enik perilaku (oomis) 157E$

2$3$1$ E,aluasi -&i To%sisitas

a"a e'aluasi hasil u&i toksisitas) "ilakukan pen#amatan umum)

pen#amatan parameter klinik) "an pemeriksaan setelah kematian$

en#amatan umum "ilakukan pen#amatan pa"a penampilan) perilaku "an

akti'itas motorik) serta semua abnormalitas hewan u&i sebelum "an sesu"ah

proses u&i toksisitas$ en#amatan parameter klinik "ilakukan pemeriksaan

hematolo#i meliputi parameter ka"ar hemo#lobin) &umlah sel eritrosit)

leukosit) "an trombosit) serta hematokrit$ Dilakukan pula u&i biokimia "arah

"an analisis urin$

a"a akhir pen#u&ian atau pemeriksaan setelah kematian semua

hewan u&i "ikorbankan "an "iperiksa patolo#inya se*ara makroskopis) &ika

kea"aan &arin#an memun#kinkan) "ilakukan pula pemeriksaan histolo#i$

11


36/112

Selain itu) berat beberapa or#an) baik "alam nilai absolut maupun relati%

terha"ap berat ba"an harus "iukur) karena ini merupakan in"ikator yan#

ber#una ba#i toksisitas$ emeriksaan ini akan men#hasilkan in%ormasi

toksisitas senyawa u&i "alam kaitannya "en#an e%ek pa"a or#an sasaran$

Cn%ormasi tersebut "apat memberikan petun&uk tentan# &enis penelitian

khusus lainnya yan# perlu "ilakukan$ 6al ini meliputi or#an sasaran "an

histolo#i or#an (misalnya hati) #in&al) anak #in&al) &antun#) "an lain-lain$

2usumawati) 2004$ Men*it memiliki banyak keun##ulan seba#ai hewan

per*obaan) yaitu siklus hi"up yan# relati% pen"ek) &umlah anak per kelahiran

banyak) 'ariasi si%at-si%atnya tin##i "an mu"ah "alam penan#anannya

(Moriwaki) 1554$ Men*it putih memiliki bulu pen"ek halus berwarna putih

serta ekor berwarna kemerahan "en#an ukuran lebih pan&an# "ari pa"a

ba"an "an kepala$ Men*it memiliki warna bulu yan# berbe"a "isebabkan

perbe"aan "alam proporsi "arah men*it liar "an memiliki kelenturan pa"a

si%at-si%at pro"uksi "an repro"uksinya (Na%iu) 155$

Determinasi men*it putih:

12


37/112

>era&aan : /nimalia

@ilum : hor"ata

Sub %ilum : Fertebrata

>elas : Mammalia

an#sa : Bo"entia

Sub ban#sa : Myomorpha

@amili : Muri"ae

Sub %amili : Murinae

Mar#a : Mus

9enis : Mus musculus (/rrin#ton) 1572$

Men*it merupakan binatan# asli /sia) Cn"ia "an ,ropa arat)

termasuk "alam keluar#a Bo"entia sehin##a masih termasuk kerabat

hamster) tupai "an makhluk pen#erat lainnya (6aria"i) 2012$

Men*it "ian##ap "ewasa setelah berumur 38 hari) berat ba"an

"ewasa tubuh men*it &antan "an betina se*ara berturut-turut 20-40 # "an 1E-

38 #$ >on"isi men*it se*ara keseluruhan terutama ber#antun# pa"a kualitas

makanan yan# "iberikan "an lin#kun#an hi"up men*it yan# mempen#aruhi

reaksi terha"ap pen#obatan (Smith "an Man#koewi"&o&o) 15EE$

>an"an# men*it biasanya berupa kotak yan# terbuat "ari plastik

atau metal "en#an kawat kasa seba#ai penutup ba#ian atas kan"an#$

>elen#kapan lain yan# "iperlukan yaitu tempat pakan) tempat minum) "an

alas kan"an#$ Men*it-men*it yan# "iper#unakan untuk penelitian yan# lama

"itempatkan "alam kan"an# yan# berukuran 22)8 *m < 10 *m untuk ti#a

ekor men*it (eter) 157$ Syarat yan# harus "ipenuhi untuk kan"an#

men*it yaitu) kan"an# harus memiliki luas yan# *ukup sehin##a men*it

bebas "apat ber#erak "an ti"ak ter#an##u$ Men*it sebaiknya "itempatkan

"alam kon"isi yan# re"up atau a#ak #elap "en#an *ahaya kuran# "ari 0 lu<

terutama untuk men*it albino$ >an"an# ti"ak boleh "itempatkan pa"a

13


38/112

"aerah yan# bisin#) lembab "an ber"ebu serta yan# palin# pentin# a"alah

bahwa men*it lebih menyukai tempat yan# #elap (Bakhma"i) 200E$

enutup lantai kan"an# atau be""ing ) merupakan penyerap untuk

menampun# kotoran termasuk air ken*in# "an sisa-sisa makanan$

emakaian be""ing mempunyai ti#a tu&uan) yaitu untuk menyerap kotoran)

melen#kapi bahan saran# "an untuk isolasi panas (.reen) 15E$

Men*it "ewasa "apat men#konsumsi pakan 3-8 #hari$ at-!at

makanan yan# "ibutuhkan seekor men*it a"alah protein kasar 20-28)

ka"ar lemak 10-12 ) ka"ar pati 44-48) ka"ar serat kasar maksimal

4 "an ka"ar abu 8- (Smith "an Man#kowi"&o&o) 15EE$

/ir minum yan# "ibutuhkan oleh setiap ekor men*it berkisar antara

4-E ml sehari (Malole "an ramono) 15E5$ /ir minum yan# "ikonsumsi

harus selalu terse"ia "an bersih karena men*it menyukai air yan# baru$

Seekor men*it mu"ah sekali kehilan#an air sebab e'aporasi tubuhnya yan#

tin##i$ Antuk menekan stres yan# "apat memi*u kanibalisme maka air

minum &u#a san#at "ibutuhkan$

ara yan# benar "alam meme#an# men*it yaitu "en#an meme#an#

ba#ian ten#ah ekor men*it$ eher "ipe#an# "en#an tan#an kanan "an

&an#an terlalu "itekan) &ari telun&uk "an ibu &ari meme#an# ku"uk "an &ari

kelin#kin# men&epit ekor (Moriwaki) 1554$

Men*it &antan "an betina mu"a sukar untuk "ibe"akan$ ;estis pa"a

men*it &antan terlihat san#at &elas pa"a saat matan# seksual) berukuran

relati% besar "an biasanya ti"ak tertutup oleh rambut$ Men*it betina mu"ah

untuk "ikenali karena &arak antara luban# anus "an luban# #enitalnya yan#

ber"ekatan$ (Muliani) 2011$

14


39/112

2


40/112

Daerah reser'oir ini ter"iri "ari $un"us "an 13 cor+us) se"an#kan

antral pump ter"iri "ari cor+us2 antrum2 "an +ylorus (Bhoa"es an"

;anner) 2003$

2$8$1$2$ (ungsi ambung

ambun# memiliki beberapa %un#si) yaitu antara lain :

o @un#si motorik

@aktor terpentin# "alam %un#si motorik a"alah %un#si

penyimpanan makanan yan# masuk sehin##a "apat "i*erna "an

"iserap usus "en#an optimal$ @un#si motorik ini terba#i men&a"i

ti#a) yan# pertama yaitu menyimpan makanan "alam &umlah besar

sampai makanan tersebut "apat "itampun# pa"a saluran *erna

ba#ian bawah) %un#si yan# ke"ua a"alah men*ampur makanan

tersebut "en#an sekret lambun# sehin##a membentuk suatu

*ampuran seten#ah pa"at yan# "inamakan kimus) "an %un#si

motorik keti#a yaitu men#eluarkan makanan "en#an lambat "ari

lambun# masuk ke usus halus "en#an ke*epatan yan# sesuai untuk

pen*ernaan "an absorpsi oleh usus halus (.uyton) 1550$

o Sekresi

@un#si sekresi) lambun# men#eluarkan asam hi"roklori"a

(6l "an en!im-en!im yan# memulai pen*ernaan protein

(Sherwoo") 2001$ Selain sel-sel yan# menyekresi mukus yan#

membatasi permukaan lambun#) mukosa lambun# memiliki "ua

kelen&ar tubulosa) yaitu kelen&ar #astrik atau %un"us "an kelen&ar

pilorus$ >elen&ar #astrik menyekresikan #etah pen*ernaan "an

kelen&ar pilorus menyekresikan hampir seluruhnya mukus untuk

perlin"un#an mukosa pilorus$ >elen&ar #astrik terletak "i

sembaran# tempat "alam mukosa korpus "an %un"us lambun#)

se"an#kan kelen&ar pilorus terletak pa"a ba#ian antrum lambun#

(.uyton) 1550$

16


41/112

o /bsorpsi

ambun# merupakan "aerah saluran *erna yan# "aya

absorpsinya &elek$ 6anya beberapa !at yan# larut "alam lemak)

seperti alkohol "an beberapa obat-obatan "apat "iabsorpsi "alam

&umlah se"ikit (.uyton) 1550$

en*ernaan makanan "alam lambun# ter&a"i san#at

se"ikit$ Namun beberapa !at #i!i men#alami pen*ernaan "ari

beberapa sekret lambun#) yaitu karbohi"rat) protein) "an lemak

(.uyton) 1550$

2$8$1$3$ 3erusa%an ambung

>onsumsi obat-obatan seperti asam asetilsalisilat) atau obat

NS/CDs "apat menimbulkan suatu kea"aan pera"an#an atau pen"arahan

mukosa lambun# yan# bersi%at akut) kronis) "i%us "an lokal$ 6al ini biasa

"isebut "en#an #astritis (ri*e an" Syl'ia) 2008$

.astritis akut se*ara makroskopis ter"apat lesi erosi mukosa

"en#an lokasi berbe"a &ika "itemukan pa"a korpus "an %un"us) biasanya

"isebabkan oleh stress$ /pabila "isebabkan karena obat-obatan NS/CDs)

terutama "itemukan "i "aerah antrum$ /ntrum men#hasilkan hormon

#astrin yan# "ipen#aruhi oleh a"anya ran#san#an pa"a ner'us 'a#us)

makanan "an asam amino$ Se*ara mikroskopik) "itemukan reaksi sel

in%lamasi neutropil yan# minimal$ .ambar kea"aan lambun# "alam kon"isi

normal "an tukak "apat "itun&ukkan pa"a #ambar 2$8$

17


42/112

.ambar 2$8$ (/$ >ea"aan lambun# men*it "en#an kon"isi normal($ >ea"aan lambun# men*it "en#an kon"isi tukak (anak panah

(Dewi) 2012

2$8$2$ Anatomi He+ar

6epar terletak "i kua"ran kanan atas ron##a ab"omen) "ibawah

"ia%ra#ma (ri*e an" =ilson) 200$ Dalam kea"aan se#ar hepar berwarna

merah tua atau merah *oklat (eeson et al $) 1550$

Dalam hepar ter"apat 3 &enis &arin#an yan# pentin#) yaitu sel

parenkim hepar) susunan pembuluh "arah "an susunan saluran empe"u$

>eti#a &arin#an ini erat) sehin##a kerusakan satu &enis &arin#an "apat

men#akibatkan kerusakan &arin#an lain$ Diantara lembaran sel hepar

ter"apat kapiler-kapiler yan# "isebut sinusoi") sinusoi" merupakan *aban#

'ena porta "an arteri hepatika (/miru"in) 2007 ri*e "an =ilson) 1554$

.ambar anatomi hepar pa"a manusia "apat "itun&ukkan pa"a #ambar 2$$

18


43/112

.ambar 2$$ /natomi hepar (Bohen) Yoko*hi an" ut&en-Dre*ol) 200>eteran#an .ambar : (1$ ;ulan# rusuk (2$ Dia%ra#ma (3$ ermukaan hepar pa"a

"ia%ra#ma (4$ igament (alci$orm (8$ upin# kanan hepar ($ (un"us o$ gallbla""er (7$

igament gastro%oli% (E$ +mentum besar (5$ /orta (10$ ,so%a#us (11$ upin# kiri hepar

(12$ ambun# (13$ i#amentum teres (14$ Asus besar

2$8$2$1$ (isiologi He+ar

6epar merupakan or#an internal terbesar "alam tubuh) "imana

beratnya sekitar 2)8 berat ba"an oran# "ewasa$ Selama istirahat) hepar menerima 28 "ari luaran paru melalui 'ena portal hepatik) "an arteri

hepatik$ Fena hepatik portal membawa nutrisi terabsorbsi "ari 4# tract ke

hepar) "imana nutrien-nutrien itu akan "iambil) "isimpan) "an

"i"istribusikan) termasuk &u#a 'itamin$ 6epar meme#an# peranan pentin#

"alam men&a#a ka"ar #lukosa "alam "arah$ 6epar &u#a mere#ulasi sirkulasi

"ari "arah lipi") "en#an mensekresikan se&umlah ,ery low "ensity

li+o+roteins (FDs$ >ebanyakan "ari sirkulasi protein plasma "isintesis

oleh hepar$ 6epar men#ambil senyawa-senyawa toksik "an obat-obat "ari

sirkulasi portal$ 6epar &u#a berperan seba#ai or#an ekskretori untuk pi#men

empe"u) kolesterol "an obat-obat$ a"a akhirnya) hepar men&alankan %un#si

pentin# en"okrin (Bhoa"es an" ;anner) 2003$

19


44/112

6epar merupakan or#an utama seba#ai pertahanan terha"ap in'asi

bakteri "an a#en toksik (rin*e an" =ilson) 1558$ 6ampir semua substan

yan# masuk ke "alam tubuh "an men#ikuti sirkulasi sistemik akan

"imetabolisme "i hepar$ a"a hepar ter"apat hepatosit yan# men#an"un#

banyak en!im yan# "i#unakan seba#ai katalisator "alam metabolisme

substan) termasuk obat "an makanan (.uyton) 155$ ,n!im yan# spesi%ik

"iamati untuk monitorin# %un#si hepar a"alah Serum 4lutamic 5iru,ic

Transaminase (S.; atau Alanine Aminotrans$erase (/;$ ,n!im ini

se*ara normal bera"a "i "alam sel hepar$ Namun &ika ter&a"i kerusakan) sel

hepar akan melepaskan en!im ini ke "alam "arah$ enin#katan ka"ar en!im

ini "i "alam "arah menun&ukan kerusakan hepar (aron) 1550$

2$8$2$2$ Histologi He+ar

Se*ara makroskopis) hepar terba#i men&a"i empat lobus yaitu

"en#an lobus utamanya a"alah lobus "ekstra "an lobus sinister) se"an#kan

lobus lainnya a"alah lobus kua"rantus "an lobus kau"atus$ obus hepar

memiliki struktur heksa#onal "en#an "iameter 1-2 mm) ter"iri "ari kapsula

%ibrosa "an kapsula serosa$ ;iap lobus hepar terba#i men&a"i struktur yan#

"inamakan lobulus$ obulus merupakan unit mikroskopis "an %un#sional

or#an hepar$ Se*ara mikroskopis hati manusia ter"apat 80$000 sampai

100$000 lobulus$ Setiap lobulus berbentuk heksa#onal yan# ter"iri atas

lembaran sel epari berbentuk kubus yan# tersusun ra"ial men#elilin#i 'ena

sentralis (.uyton "an 6all) 1554$

Sel hepar atau hepatosit merupakan struktur utama hepar yan#

tersusun "ari lempen#an-lempen#an ber*aban# yan# salin# berhubun#an

"an membentuk anyaman ti#a "imensi "en#an lempen#an-lempen#an ini

men#elilin#i 'ena sentralis (Dellman an" rown) 1552$ ;ebal susunan sel

ini hanya satu lapis$ Sel intinya berbentuk bulat "an terletak "i ten#ah serta

20


45/112

memiliki satu atau lebih nukleolus "en#an kromatin yan# menyebar pa"a

ba#ian peri%er) tapi serin# pula "itemukan "ua inti yan# "isebabkan

pemba#ian ti"ak sempurna "ari sitoplasma akibat pembelahan inti$ 9umlah

sitoplasma ter#antun# "ari &umlah nutrisi seseoran#) &ika oran# "en#an #i!i

baik maka hepatosit akan menyimpan banyak #liko#en "an men#olah lipi"

"alam &umlah yan# besar (umon##a) 200E$ .ambaran histolo#i masin#-

masin# ba#ian anatomi hepar "i&elaskan melalui #ambar 2$7$ O 2$11$

.ambar 2$7$ obulus hepar (>uehnel) 2003

>eteran#an : (1$ Fena sentral (2$ er*aban#an #lissonewarnaan : a!an Mikroskop *ahaya erbesaran : 400 <

.ambar 2$E$ Sinus hepar (>uehnel) 2003

>eteran#an : (1$ Fena sentral (2$ Sel >up%%er pa"a sinus hepar

Semithin section ewarnaan : Methylene blue-a!ure Mikroskop

*ahaya erbesaran : 400 <

21


46/112

.ambar 2$5uehnel) 2003

>eteran#an : (1$ Sinus hepar "en#an en"othelium ter%enestrasi (2$ >anakuli empe"u (3$

Nukleus (4$ elah DisseMikroskop elektron erbesaran : 4000 <

.ambar 2$10$ ,mpe"u kanalikuli (>uehnel) 2003

>eteran#an : (1$ Fena interlobular pembenaman sil'er #ol#i Nukleus "iwarnai

"en#an karmin merah Mikroskop *ahaya

erbesaran : 180 <

22


47/112

.ambar 2$11$ Struktur histolo#i hepar men*it (perbesaran 400


48/112

1554$ Nekrosis &u#a "apat "iartikan seba#ai proses perubahan mor%olo#i

seba#ai akibat tin"akan "e#enerasi pro#resi% oleh en!im-en!im pa"a sel

yan# ter&e&as letal (Bobbins an" /n#ell) 157$ >apasitas *a"an#an hepar

"apat habis apabila hepar terkena penyakit yan# menyeran# seluruh

parenkim hepar sehin##a timbul kerusakan pa"a hepar (Bobbins et al.)

2003$

Amumnya perubahan-perubahan yan# ter&a"i pa"a sel nekrotik

"apat ter&a"i pa"a semua ba#ian sel$ etun&uk yan# palin# &elas pa"a

kematian sel a"alah perubahan pa"a inti sel$ a#ian sel yan# telah mati

intinya akan menyusut) batas ti"ak teratur "an berwarna #elap$ roses ini

"inamakan piknosis "an intinya "isebut piknotik (ri*e an" =ilson) 1554$

Nekrosis hepar akibat peroksi"ase lipi" maupun ra"ikal bebas

"apat bersi%at %okal) sentral) perten#ahan) peri%er atau masi%$ >ematian sel

ter&a"i bersamaan "en#an pe*ahnya membran plasma$ erubahan

mor%olo#is awal berupa e"ema sitoplasma) "ilatasi retikulum en"oplasma

"an "isa#re#asi polisom$ ;er&a"i akumulasi tri#liseri" seba#ai butiran lemak

"alam sel "an ter&a"i pemben#kakan mitokon"ria pro#resi% "en#an

kerusakan krista (=enas) 155$ Sta"ium selan&utnya sel "apat men#alami

"e#enerasi hi"ropik) susunan sel yan# terpisah-pisah) inti sel piknotik

(kariopiknosis yaitu pen#erutan inti sel "an kon"ensasi kromatin$

>emu"ian ter&a"i karioreksis yaitu %ra#mentasi inti yan# menin##alkan

pe*ahan-pe*ahan sisa inti berupa !at kromatin yan# tersebar "i"alam sel$

Selan&utnya ter&a"i kromatin baso%il men&a"i pu*at yan# "inamakan

kariolisis$ Den#an per&alanan waktu) ter&a"i pen#han*uran "an pelarutan inti

sel sehin##a inti sel sama sekali men#hilan#) pe*ahnya membran plasma)

"an nekrosis (;homas) 15EE

24


49/112

2$8$3$ Anatomi 4in&al

.in&al merupakan salah satu or#an "alam sistem uriner

(Dellmann an" rown) 1552$ Sistem uriner a"alah sistem or#an utama

yan# berperan "alam homeostasis air "an elektrolit) serta berperan "alam

ekskresi sisa hasil metabolisme tubuh (urkitt et al.) 1558$ Sistem tersebut

ter"iri "ari sepasan# #in&al) sepasan# ureter) serta kan"un# kemih "an uretra

(Dellmann an" rown) 1552$ @un#si utama sistem uriner "ilakukan oleh

#in&al) yaitu men#atur komposisi "an 'olume *airan tubuh (Seeley et al.)

2002$

.in&al ber&umlah sepasan#) berbentuk seperti ka*an#) berwarna

kemerahan) "an terletak "alam retroperitoneum pa"a "in"in# posterior

ab"omen$ osisi hati menyebabkan letak #in&al kanan bera"a sekitar 1-2 *m

lebih ren"ah "iban"in#kan #in&al kiri$ Masin#-masin# #in&al memiliki berat

130-180 #ram "en#an ukuran pan&an# sekitar 11 *m) lebar sekitar 4-8 *m)

"an tebal sekitar 3 *m (.artner an" 6iatt) 2007$ a"a kea"aan pembesaran

massa #in&al "apat "itan"ai "en#an per#eseran lemak perine%rik (,%%en"i

"an Markum) 2007$ .ambar struktur #in&al "apat "itun&ukkan pa"a #ambar

2$12$

.ambar 2$12$ /natomi #in&al (@o*osi) 2005

25


50/112

ermukaan luarnya halus "an li*in) "iselubun#i oleh simpai

(ca+sula yan# "ilin#kupi oleh %asia .erota "an &arin#an lemak perine%rik$

a"a sisi me"ial #in&al ter"apat *ekun#an yan# "isebut hilus (hillum o$

%i"ney "imana merupakan tempat masuknya sara%) keluar "an masuk

pembuluh "arah "an pembuluh lim%e yan# "itembus oleh arteri "an 'ena

renalis) no"ul lim%atikus) "an ureter$ a"a irisan koronal #in&al tampak

parenkim #in&al yan# terba#i men&a"i ba#ian korteks (renal cortex "an

me"ula (renal me"ulla) "en#an ton&olan korteks "isebut kolumna renalis

(renal column) "an to&olan me"ula "isebut papila renalis (renal +a+ila

(9unPueira et al.) 2008

2$8$3$1$ Histologi 4in&al

.in&al apabila "ipoton# membu&ur ter"apat parenkim yan#

berwarna merah #elap pa"a ba#ian luar yan# "isebut korteks "an yan#

berwarna lebih *erah pa"a ba#ian "alam "isebut me"ula (.uyton "an 6all)

1557$ .in&al manusia umumnya ter"iri atas enam papilla tetapi pa"a

men*it hanya ter"apat satu papilla$ .lomerulus "ibun#kus oleh kapsul

owmann se"an#kan kapiler #lomerulus "ilapisi oleh sel-sel epitel$ airan

yan# "i%iltrasi "ari kapiler #lomerulus akan men#alir ke "alam kapsul

owmann "an kemu"ian masuk ke "alam tubulus proksimal yan# terletak

pa"a korteks #in&al (.uyton "an 6all) 1557$

;ubulus kontortus proksimal ter"apat banyak pa"a korteks #in&al

"en#an "iameter sekitar 0 Qm "an pan&an# sekitar 14 mm$ ;ubulus

kontortus proksimal ter"iri "ari pars kon'ulata yan# bera"a "i "ekat korpus

kulus #in&al "an pars rekta yan# ber&alan turun "i me"ula "an korteks)

kemu"ian berlan&ut men&a"i len#kun# 6enle "i me"ula$ @un#si "ari tubulus

kontortus proksimal a"alah men#uran#i isi %iltrat #lomerulus E0-E8 yaitu

26


51/112

"en#an *ara mereabsorpsi melalui transport "an pompa natrium &u#a

senyawa-senyawa lain seperti #lukosa) asam amino) protein "an bikarbonat$

,pitel yan# melapisi tubulus ini a"alah selapis kuboi" yan# menun&an#

"alam mekanisme absorbsi "an eksresi$ +bat akan terlebih "ahulu akan

"ikonsentrasikan "alam sel tubulus proksimal #in&al sebelum "iekskresikan

melalui urin$ +leh karena ter&a"i absorbsi "an ekskresi akti% tubulus

proksimal) maka ka"ar toksik pa"a tubulus proksimal menin#kat$ Maka

tempat ini serin# men&a"i sasaran e%ek toksik (ri*e "an =ilson) 1554$

;ubulus kontortus "istal merupakan ba#ian terakhir "ari ne%ron$

;ubulus ini "ilapisi oleh sel-sel epitel selapis kuboi"$ Sel epitel tubulus

san#at peka terha"ap anoksia "an rentan terha"ap toksin$ eberapa %aktor

memu"ahkan tubulus men#alami toksik) termasuk permukaan bermuatan

listrik yan# luas untuk reabsorbsi tubulus) sistem transpor akti% untuk ion

"an asam or#anik) "an kemampuan melakukan pemekatan se*ara e%ekti%)

selain itu ka"ar sitokrom 480 yan# tin##i untuk men"etoksi%ikasi atau

men#akti%kan toksikan (otran "kk$) 2007$ .ambar histolo#i tubulus "an

#lomerulus #in&al "apat "itun&ukkan pa"a #ambar 2$13 "an #ambar 2$14$

.ambar 2$13$ ;ubulus #in&al (>uehnel) 2003

>eteran#an : (1$ ;ubulus proksimal (2$ ;ubulus "istalewarnaan : ;rikrom

Masson-.ol"ner Mikroskop *ahaya erbesaran : 400 <

27


52/112

.ambar 2$14$ .lomerulus #in&al (>uehnel) 2003

>eteran#an #ambar : (1$ >apiler (2$ ela owman (3$ >apsul owman (4$

Nukleus sel en"otelial (8$ Nukleus po"osit Mikroskop ,lektron erbesaran : 2000 <

2$8$3$2$ (ungsi 4in&al

.in&al memiliki peranan pentin# "alam mempertahankan

homeostasis *airan tubuh$ 6al tersebut "isebabkan karena #in&al

men#eksresikan seba#ian besar pro"uk akhir metabolisme tubuh$ +r#an

tersebut berperan "alam men#ontrol sekresi hormon-hormon al"osteron "an

/D6 yan# berperan "alam men#atur &umlah *airan tubuh$ .in&al &u#a

men#atur metabolisme ion kalsium "an 'itamin D) serta men#hasilkan

beberapa hormon) seperti eritropoetin yan# ber%un#si "alam pembentukan

sel "arah merah "an renin yan# ber%un#si untuk men#atur tekanan "arah

(Setia"i) 2007$

Salah satu mekanisme #in&al "alam men#atur komposisi "an

'olume *airan tubuh a"alah "en#an men#ontrol 'olume "arah$ Seba#ian

besar 'olume "arah men#alir melewati #in&al (Seeley et al.) 2002$

28


53/112

eberapa substansi "alam "arah yan# ti"ak "ibutuhkan la#i oleh tubuh akan

"iseleksi oleh #in&al) kemu"ian "ieksresikan "alam bentuk urin (.uyton

an" 6all) 200$

2$8$3$3$ 3erusa%an 4in&al

.in&al a"alah salah satu or#an sasaran utama "ari e%ek toksik$ 6al

tersebut "isebabkan #in&al memiliki 'olume aliran "arah yan# tin##i)

sehin##a "apat men#konsentrasikan toksikan pa"a %iltrat "i "alam tubuh)

membawa toksikan melalui sel tubulus) serta men#akti%kan toksikantertentu$ Selain itu) urin yan# "ihasilkan oleh #in&al merupakan &alur utama

ekskresi seba#ian besar toksikan (u) 1558$ Cn"ikasi #an##uan #in&al "apat

"iamati "ari ren"ahnya nilai bersihan kreatinin) yan# "isebabkan ka"ar

kreatinin serum &auh lebih tin##i "ari pa"a ka"ar kreatinin yan#

"iekskresikan melalui urin (Scottish #ntercollegiate 4ui"elines !etwor% )

200E$.in&al membuan# toksikan "ari tubuh melalui mekanisme yan#

"i#unakan untuk membuan# hasil akhir metabolisme$ Mekanisme tersebut

ter"iri "ari %iltrasi #lomerulus) "i%usi tubuler) "an sekresi tubuler$ >apiler

#lomerulus memiliki pori-pori yan# besar (70 nm$ 6al tersebut

menyebabkan seba#ian besar toksikan "apat melewati #lomerulus "an

men#alami absorpsi pasi% "i sel-sel tubuler$ +leh karena itu) setiap ba#ian

ne%ron) seperti #lomerulus se*ara potensial "apat "irusak oleh e%ek toksikan$

>erusakan yan# "itimbulkan oleh toksikan "apat bera#am) mulai "ari

perubahan biokimia atau sampai kematian sel (u) 1558$ >erusakan pa"a

#lomerulus umumnya berupa nekrosis (+la#un&u et al.) 2005) yan# "isebut

&u#a kematian sel (An"erwoo") 1555$

29


54/112

a#ian "alam #in&al yan# palin# rentan terha"ap e%ek toksikan

a"alah tubulus kontortus proksimal$ 6al tersebut "isebabkan absorpsi "an

sekresi akti% yan# ter&a"i "i "alam tubulus tersebut$ Selain itu) ka"ar

sitokrom -480 pa"a tubulus kontortus proksimal lebih tin##i untuk

men"etoksi%ikasi toksikan$ o#am berat) seperti merkuri) kromium)

ka"mium) "an timbal) "apat men#ubah %un#si tubulus yan# "itan"ai "en#an

#likosuria) aminoasi"uria) "an poliuria (u) 1558$ entuk kerusakan sel

tubulus proksimal "apat berupa penutupan lumen tubulus (+la#un&u et al.2

2005$

erubahan histolo#i #in&al akibat toksikan "apat "iukur "en#an

men##unakan meto"e analisis mor%ometri$ /nalisis tersebut bertu&uan untuk

men#etahui seberapa besar kerusakan #in&al yan# "isebabkan oleh toksikan$

atera et al. (200 "alam penelitiannya tentan# mor%ometri "an

abnormalitas %un#si #in&al pa"a anak men*it yan# "iberi *okelat selama

masa kehamilan "an laktasi) melakukan analisis mor%ometri "en#an

menentukan total area korteks) &umlah sel-sel #lomerulus) "an "iameter

#lomerulus$ >erusakan pa"a #in&al men*it yan# men#alami nekrosis pa"a

tubulus "apat "ilihat pa"a #ambar 2$18$

.ambar 2$18$ >erusakan #in&al men*it ( Mus musculus ewarnaan 6, erbesaran

400eteran#an: .L .lomerulus N;L Nekrosis tubulus BL Cn%iltrasi sel ra"an# (Suhenti)

2007

30


55/112

2


56/112

pasti "alam pen#ertian kean#kaan melainkan berupa skor yan# berupa

&en&an# atau rankin# (D&arwanto) 2007$ Menurut D&arwanto (2007 u&i

statistik nonparametrik "apat "i#unakan "alam kon"isi "imana) bentuk

"istribusi populasinya "ari sampel atau sampel-sampel penelitian yan#

"iambil ti"ak "iketahui menyebar se*ara normal) 'ariabel penelitiannya

hanya "apat "iukur "alam skala nominal "an skala or"inal) ukuran sampel

atau sampel-sampel penelitiannya ke*il "an si%at "istribusi populasinya

ti"ak "iketahui se*ara pasti$ ontoh meto"e statistik nonparametrik a"alah

u&i >ruskal-=allis (beberapa sampel ti"ak berhubun#an) u&i hi-sPuare) u&i

Me"ian) u&i @rie"man "an Mann-=hitney ("ua sampel ti"ak berhubun#an$

32


57/112

BAB III

METODE PENELITIAN

3


58/112

tertentu (3 # makananhari a#ar penin#katanpenurunan berat ba"an bukan

"ikarenakan &umlah makanan yan# berbe"a$

3


59/112

yan# su"ah "ikalikan "en#an %aktor kon'ersi "ari "osis manusia ke men*it

(0)002 yaitu 800 m#70 >#) 1000 m#70 ># "an 1800 m#70

># atau 1)3 m#20 #) 2) m#20 # "an 3)5 m#20 #$ Bentan#

"osis untuk pemakaian asam asetilsalisilat a"alah 300-500 m# tiap 4- &am

sehin##a men&a"i a*uan pemilihan "osis untuk pemberian suspensi

senyawa u&i ber"asarkan "osis la!im a"alah "ari "osis tertin##i hin##a "osis

terke*il yan# ti"ak menimbulkan kematian pa"a hewan *oba$ Folume

pemberian se*ara per oral sebesar 0)2 ml untuk 20 # berat men*it) men#a*u

pa"a aturan +,D 407 (1558 yaitu 1 ml100 #$ ;abel 3$1$ menun&ukkan

%ormulasi suspensi senyawa u&i "an pemban"in#$

;abel 3$1 @ormula suspensi senyawa u&i "an pemban"in#

/sam

2-(4-(klorometilben!oiloksiben!oat

/sam

/setilsalisilat

Dosis 1)3

m#

20

#

2)

m#

20

#

3)5 m#

20 #

1)3m#

20#

Senya

wa

8 m# 130

m#

158 m# 8 m#

./ 3 3 3 3/Pua"e

st a"

10 ml 10

ml

10 ml 10 ml

3$3$3$ 5embuatan Da+ar (ormalin

ahan-bahan untuk membuat 1 liter netral bu%%er %ormalin 10)

a"alah "en#an menimban# %ormalin (0 b' %ormal"ehi" 100 ml

Na62+4$2620 monohi"rat 10)0 # Na26+4 anhi"rat 12)8 # "an /Pua"est

a" 1000 ml$ Masin#-masin# "iukur p6 komponennya) kemu"ian masin#-

masin# "ilarutkan "en#an Na62+4$2620 "an Na26+4 pa"a se"ikit

aPua"est$ arutan Na62+4$2620 "i*ampur "en#an larutan %ormalin (0

b' %ormal"ehi") lalu larutan asam (Na62+4$2620%ormalin "i*ampur

35


60/112

"en#an larutan basa (Na26+4 perlahan-lahan sambil "ia"uk$ Semua

komponen harus terlarut$ p6 "i*ek men##unakan p6 meter$ Setelah itu

en*erkan "en#an aPua"est sampai 'olume tepat 1000 ml$ p6 akhir larutan

"i*ek "an "ipertahankan pa"a p6 netral (T7$

3$3$4$ 5emberian Se"iaan -&i "an Se"iaan 5emban"ing

emberian 'olume obat ter#antun# "ari berat ba"an men*it$ Folume

pemberian suspensi obat "apat "ihitun# "en#an men##unakan rumus:

Folume in&eksi L

Dosis

1000 g <Berat Badan Mencit

Konsentrasi Suspensi Obat

Misalnya men*it "en#an berat ba"an 30 # akan "iberi obat "en#an

"osis 1800 m#># maka 'olume pemberiannya a"alah:

1500mg

1000g <30g

150mg/ml L 0)3 ml

9a"i pemberian se"iaan "en#an "osis 1800 m# ># untuk

men*it "en#an berat ba"an 30 # a"alah 0)3 ml$ Folume pemberian se"iaan

untuk "osis yan# lain "an "en#an berat ba"an men*it yan# berbe"a "ihitun#

"en#an *ara yan# sama$

3$3$8$ 5ersia+an Hewan Coba

a"a persiapan ini) "isiapkan 48 ekor men*it berbobot 20-38 # yan#

"iba#i men&a"i lima kelompok yaitu kelompok u&i "en#an "iberi senyawa

asam 2-(4-(klorometilben!oiloksiben!oat (1)3 m#20 # 2) m#20

# 3)5 m#20 # sebanyak 18 ekor men*it &antan) kelompok kontrol

positi% yan# "iberi senyawa asam asetilsalisilat (1)3 m#20 # sebanyak 8

ekor men*it &antan) kelompok kontrol ne#ati% yan# "iberi larutan ./ 3

sebanyak 8 ekor men*it &antan) kelompok satelit u&i yan# "iberi senyawa

asam 2-(4-(klorometilben!oiloksiben!oat (1)3 m#20 # 2) m#20

36


61/112

# 3)5 m#20 # sebanyak 18 ekor men*it &antan) kelompok satelit

kontrol positi% yan# "iberi senyawa asam asetilsalisilat (1)3 m#20 #

sebanyak 8 ekor men*it &antan$

Sebelum per*obaan) hewan *oba "ipuasakan selama E &am) ti"ak

"iberi makan namun tetap "iberi minum$ Saat "ilakukan u&i akti'itas) setiap

men*it "itimban# terlebih "ahulu untuk men#etahui berat ba"an masin#-

masin# sehin##a "apat "ihitun# besar "osis yan# "apat "iberikan kepa"a

hewan *oba$

3$3$$ 5ela%sanaan -&i To%sisitas Sub%ronis

Men*it akan men#alami pemaparan senyawa sehari sekali selama

2E hari "en#an "iberi asam 2-(4-(klorometilben!oiloksiben!oat 1)3 m#20

#) 2) m#20 # "an 3)5 m#20 #) asam asetil salisilat 1)3 m#20

# "an pembawa "en#an 'olume pemberian sebesar 0)2 ml20 # se*ara

per oral sesuai kelompok perlakuan$ Setelah pemaparan senyawa selama 2E

hari) semua men*it "alam pen#u&ian toksisitas subkronis (ke*uali kelompok

satelit akan "ibe"ah$ Sebelum "ibe"ah) men*it akan "ieutanasia "en#an

men##unakan eter$ Men*it yan# telah "ibe"ah) kemu"ian "iambil or#annya

yan# meliputi hepar) lambun# "an #in&al$ +r#an-or#an tersebut "imasukkan

ke"alam wa"ah yan# su"ah berisi "apar %ormalin 10 untuk men#hin"ari

ter&a"inya kerusakan selama proses penyimpanan$ a"a hari ke-25)

kelompok satelit ti"ak "ilakukan pembe"ahan "an selama 14 hari kelompok

satelit ti"ak "iberikan pemaparan senyawa$ en#amatan pa"a kelompok

satelit "ilakukan sama "en#an pen#amatan pa"a kelompok perlakuan$

3$3$7$ 5embuatan 5re+arat Histologis 5ewarnaan HE ( Hematoxylin

ErlichEosin

Meto"e ini "imaksu"kan untuk melihat kea"aan struktur yan#

lebih &elas "ari or#an yan# akan "iteliti$ Den#an meto"e 6,) hampir semua

ma*am &arin#an "apat "ipoton# "en#an baik "an hasil irisannya pun "apat

37


62/112

lebih tipis$ Namun kekuran#an "ari meto"e ini a"alah &arin#an akan

men&a"i lebih keras) men#erut "an mu"ah patah$ roses pembuatan preparat

"en#an men##unakan pewarnaan 6, ini a"alah seba#ai berikut:

1$ @iksasi

Sebelum "i%iksasi or#an hewan per*obaan "i*u*i men##unakan larutan

#aram %isiolo#is (Nal 0)5) kemu"ian "imasukkan ke "alam larutan

"apar %ormalin 10 "an "iinkubasi selama 24 &am (/ryu"hani) 2011$

2$ Dehi"rasi

Setelah semua or#an ter%iksasi maka "ilakukan proses pen*u*ian$ 6al ini

bertu&uan untuk men#hilan#kan larutan %iksasi "ari or#an$ en*u*ian

"ilakukan "en#an men##unakan alkohol bertin#kat) "ari konsentrasi yan#

ren"ah (70 hin##a konsentrasi tin##i (58$ ;u&uan proses ini a"alah

untuk menarik air "ari "alam or#an a#ar seluruh ruan#-ruan# antar sel

"alam or#an "apat "iisi "en#an molekul-molekul para%in (Suntoro "kk$)

15E3$

3$ en&ernihan

Setelah proses "ehi"rasi "ilakukan) "ilan&utkan "en#an proses pen&ernihan

"en#an men##unakan xylol selama 20 menit sampai 1 &am ter#antun# "ari

besar ke*ilnya or#an$ 6al ini bertu&uan untuk men#etahui bahwa proses

"ehi"rasi yan# "ilakukan su"ah sempurna atau belum$ en&ernihan

"ilakukan "en#an *ara menarik alkohol atau "ehi"ran lain "ari "alam or#an

sehin##a or#an terlihat transparan$ 9ika proses "ehi"ran ti"ak "ilakukan

"en#an sempurna) maka or#an ti"ak akan terlihat transparan$ ila hal ini

ter&a"i) maka or#an harus "ikembalikan kembali ke "alam "ehi"ran (alkohol

absolut untuk beberapa saat (Suntoro "kk$) 15E3 /ryu"hani) 2011$

4$ Cn%iltrasi ara%in

38


63/112

roses in%iltrasi para%in "ilakukan "en#an men##unakan para%in (para%in C)

CC) CCC yan# memiliki titik *air antara 80-8o) "ilakukan "alam o'en atau

inkubator "en#an suhu kira-kira 8-70o$ +r#an "imasukkan ke "alam

para%in murni C selama 30-0 menit ter#antun# "ari besar atau ke*ilnya

or#an) selan&utnya "imasukkan ke para%in CC selama 30-0 menit "an

terakhir masukkan ke "alam para%in CCC selama 30-0 menit$ 6al ini

bertu&uan untuk men*e#ah se&umlah besar !at pen&ernih yan# tertahan "i

"alam &arin#an serta a#ar poton#an or#an ti"ak "apat menyerap air (Suntoro

"kk$) 15E3 /ryu"hani) 2011$

8$ Embe""ing

;eknik ini biasanya "isebut seba#ai blok or#an$ enanaman untuk

membuat blok or#an "ilakukan "en#an men##unakan para%in$ Mula-mula

"en#an menyiapkan *etakan yan# memiliki ukuran yan# sama "en#an

sampel or#an seperti kotak-kotak atau menyiapkan lo#am-lo#am berbentuk

) kemu"ian "iambil larutan para%in murni ke "alam tempat penanaman

or#an) selan&utnya or#an "iambil "en#an *epat "ari para%in CCC

men##unakan pinset) masukkan ke "alam kotak penanaman yan# telah

berisi para%in$ +r#an "iletakkan "en#an posisi ba#ian yan# akan "ipoton#

pa"a ba#ian bawah (untuk mempermu"ah pelepasan) permukaan ba#ian

"alam "iberi #liserin$ roses pembekuan "ilakukan se*ara perlahan-lahan

"ari permukaan palin# "alam ("asar hin##a permukaan atas "en#an *ara

menyalakan lampu spiritus "i muka o'en "ekat penanaman or#an a#ar suhu

"i sekitarnya men&a"i lebih panas) sehin##a proses pembekuan ber&alan

lambat$ 6al ini "ilakukan untuk men#hin"ari a"anya #elembun# "alam blok

para%%in$ 9ika proses pembekuan ber&alan terlalu *epat maka) para%in "apat

"i*airkan kembali "en#an men##unakan pinset atau alat lain yan#

"ipanaskan sebentar "i atas lampu spiritus kemu"ian "itempelkan pa"a

permukaan para%in (Suntoro "kk$) 15E3$

39


64/112

$ Trimming

+r#an "ikeluarkan "ari blok para%in "en#an *ara men#uran#i pan&an#

"an lebarnya "en#an pisau "en#an irisan seron# hin##a or#an bera"a 3-8

mm "ari tepi-tepinya) kemu"ian hol"er "an spatula "ibubuhi "en#an

poton#an-poton#an para%in yan# selan&utnya "ipanaskan pa"a lampu

spiritus hin##a men*air$ Sese#era mun#kin "itempelkan pa"a permukaan

blok para%in yan# men#an"un# or#an ta"i) sehin##a permukaan blok para%in

akan ikut tertempel$ Selan&utnya "ibiarkan beberapa saat a#ar para%in

membeku$ Setelah itu "ilan&utkan proses pen#irisan or#an "en#an

men##unakan mikrotom$ lok para%in yan# telah terpasan# pa"a hol"er

"ipasan# pa"a mikrotom$ oton#an pertama biasanya poton#an yan# belum

berisi or#an) namun bila poton#an su"ah sampai pa"a or#an hen"aklah

hepar-hepar karena antara irisan satu "en#an yan# lain akan ber#an"en#an

membentuk seperti pita$ Akuran tebal irisan umumnya 3-4 mikron) "en#an

luas permukaan 1


65/112

warna ke "alam &arin#an sehin##a hasil pewarnaan ti"ak akan sempurna

(Suntoro "kk$) 15E3$

5$ Staining

roses staining "imuai "en#an "epara%inasi men##unakan xylol $ 8ylol

yan# berlebih "ihisap "en#an men##unakan kertas sarin# melalui tepi-tepi

ob&ect glass. reparat "i*elup sebentar "alam alkohol 5 "ilan&utkan

"en#an E0) 70) 80) 30) lalu aPua"est$ Setelah itu) preparat

"imasukkan ke "alam larutan hematoxylin selama 3-7 "etik kemu"ian bilas

men##unakan air men#alir (air kran selama 10 menit$

Setelah selesai pewarnaan "en#an hematoxylin) or#an "imasukkan

sebentar sa&a ke "alam alkohol mulai "en#an konsentrasi 30) kemu"ian

80) "an 70$ Setelah itu masukkan ke "alam larutan eosin 0)8 ("alam

alkohol 70 selama 1-3 menit$ Antuk proses penutupannya) or#an

"imasukkan sebentar sa&a ke "alam alkohol 70) "ilan&utkan E0) 5)

"an alkohol absolut) kemu"ian kelebihan xylol "ihisap men##unakan kertas

sarin# pa"a tepi-tepi ob&ect glass$

)b&ect glass "itetesi "en#an *ana"a balsem) kemu"ian "itutup "en#an

co,er glass. Se"iaan histolo#is yan# telah selesai "iwarnai "iberi label$ a"a

label "ituliskan: nama spesies) nama or#an&arin#an) poton#an melintan#

atau membu&ur) pewarnaan yan# "i#unakan) "an tan##al pembuatan

(Suntoro "kk$) 15E3$

3$3$E$ 5engamatan +a"a )rgan -&i

a$ en#amatan mikroskopis hepar

reparat hepar akan "iamati men##unakan mikroskop "en#an

perbesaran 100


66/112

"ilihat "en#an pen#amatan "i bawah mikroskop *ahaya "an "ihitun#

&umlahnya untuk "ianalisis$ >elainan histolo#i pa"a or#an hepar

yan# "iberikan se"iaan u&i "an kelompok satelit akan "iban"in#kan

"en#an kelompok kontrol$

b$ en#amatan makroskopis lambun#$

>on"isi mukosa lambun# "iperiksa se*ara makroskopis "an

"iamati "i bawah ka*a pembesar untuk melihat bila pa"a lambun#

ter&a"i tukak atau ti"ak serta &umlah "an lebar tukak$

*$ en#amatan mikroskopis #in&al

en#amatan "ilakukan "en#an memba#i preparat "alam 8

ba#ian (atas) kiri) ten#ah) kanan) "an bawah untuk men#etahui

sampai pa"a ba#ian mana obat "apat terabsorsi sehin##a "apat

"iketahui nekrosis yan# ter&a"i$ a"a setiap ba#ian "ilihat luasnya

kerusakan sel berupa karyolisis) karyoreksis "an piknosis (lampiran

1$ >emu"ian tin#kat nekrosis pa"a #in&al "apat "ilihat "ibawah

mikroskop *ahaya "een#an perbesaran 400< "an "ihitun# &umlah

nekrosis yan# ter&a"i$

3


67/112

Merupakan 'ariabel yan# meliputi &enis kelamin men*it)

umur) berat ba"an) bahan makanan) pewarnaan) *ara

pembuatan or#an) "an waktu$

3


68/112

hari "en#an peroral ti"ak "apat men#uran#i kerusakan makroskopis

lambun# men*it &ika "iban"in#kan "en#an asam asetilsalisilat$

6i2 L emberian senyawa u&i asam 2-(4-

klorometilben!oiloksiben!oat se*ara berulan# selama 2E hari "en#an

peroral ti"ak "apat men#uran#i nekrosis hepar men*it &ika

"iban"in#kan "en#an asam asetilsalisilat$

6i3 L emberian senyawa u&i asam 2-(4-

klorometilben!oiloksiben!oat se*ara berulan# selama 2E hari "en#an

peroral ti"ak "apat men#uran#i nekrosis #in&al men*it &ika

"iban"in#kan "en#an asam asetilsalisilat$

44


69/112

3


70/112

BAB I#

HASIL PENELITIAN DAN PEMBAHASAN

4eteran#an

/ : kontrol ne#ati%

: kontrol positi% : kontrol satelit

D : u&i 1)3 m#20 #

, : u&i 2) m#20 #

@ : u&i 3)5 m#20 #. : satelit 1)3 m#20 #

6 : satelit 2) m#20 #

C : satelit 3)5 m#20 #

a : bintik-bintik merah

b : perubahan warna

46


71/112

4$1$2$ Histo+atologi He+ar

a"a penelitian ini men##unakan sampel 48 ekor men*it Swiss

webster &antan yan# "iba#i "alam 5 kelompok yan# ter"iri "ari 3 kelompok

kontrol yaitu kelompok kontrol ne#ati% (./ 3) kelompok kontrol positi%

(asam asetilsalisilat "an kelompok kontrol positi% satelit) serta kelompok

u&i yaitu kelompok senyawa u&i asam 2-(4-(klorometilben!oiloksiben!oat

1)3 m#20 #) kelompok senyawa u&i satelit asam 2-(4-

(klorometilben!oiloksiben!oat 1)3 m#20 #) kelompok senyawa u&i

asam 2-(4-(klorometilben!oiloksiben!oat 2) m#20 #) kelompok

senyawa u&i satelit asam 2-(4-(klorometilben!oiloksiben!oat 2) m#20

#) kelompok senyawa u&i asam 2-(4-(klorometilben!oiloksiben!oat 3)5

m#20 # "an kelompok senyawa u&i satelit asam 2-(4-

(klorometilben!oiloksiben!oat 3)5 m#20 #$ 9umlah sampel pa"a

masin#-masin# kelompok ter"iri "ari 8 ekor men*it yan# "itentukan se*ara

a*ak$ Semua sampel kemu"ian "iambil hepar untuk "ibuat preparat

histopatolo#is kemu"ian "ilakukan pen#amatan "en#an *ara men#hitun#

&umlah sel hepar yan# men#alami perubahan histopatolo#is (nekrosis

"en#an men##unakan mikroskop *ahaya "en#an perbesaran 400eteran#an:

>ontrol ne#ati% : ./ 3

>ontrol positi% : /sam asetilsalisilat 1)3 m#20 #

A&i : /sam 2-(4-(klorometilben!oiloksiben!oat

47


72/112

Dari hasil analisis "iatas) "apat "ilihat nilai nekrosis sel terbesar

a"a pa"a kelompok u&i 3)5 m#20 # yaitu sebesar 20E)E0) "an terke*il

a"alah pa"a kelompok kontrol satelit yaitu 185)0$ Arutan tin#kat

keparahan nekrosis ber"asarkan hasil analisis "ata "ari yan# terke*il hin##a

yan# terbesar a"alah kelompok kontrol satelit "en#an rata-rata 185)0

kelompok kontrol ne#ati% "en#an rata-rata 13)0 kelompok satelit u&i

"osis 2) m#20 # "en#an rata-rata 1)50 kelompok u&i "osis 1)3 m#20

# "en#an rata-rata 15)10 kelompok satelit "osis 1)3 m#20 # "en#an

rata-rata 173)30 kelompok satelit u&i "osis 3)5 m#20 # "en#an rata-rata

1E2)10 kelompok kontrol positi% "en#an rata-rata 1E4)20 kelompok u&i

"osis 2) m#20 # "en#an rata-rata 1E8)58 "an kelompok u&i "osis 3)5

m#20 # "en#an rata-rata 20E)E$

;abel 4$1$;abel perban"in#an nilai &umlah sel nekrosis hepar

>elompok perlakuan 9umlah sel nekrosis SD

>ontrol satelit 185)0T3)74

>ontrol ne#ati% 13)0T28)00

Senyawa satelit u&i 2) m#20 # 1)50T18)4

Seyawa u&i 1)3 #20 # 15)10T17)28

Senyawa satelit u&i 1)3 m#20 # 173)30T34)13

Senyawa satelit u&i 3)5 m#20 # 1E2)10T22)E7

>ontrol positi% Senyawa u&i 2) m#20 #

Senyawa u&i 3)5 m#20 #

1E4)20T32)41E8)58TE)E3

20E)E0T12)43

>eteran#an:

>ontrol ne#ati% : ./ 3

>ontrol positi% : /sam asetilsalisilat 1)3 m#20 #Seyawa u&i : asam 2-(4-(klorometilben!oiloksiben!oat

48


73/112

;abel 4$2$ ;abel hubun#an perban"in#an antar kelompok (;ukey

>el$ > (- > ( > (S A1 A2 A3 S1

> (- - - - - - -

> ( - - - - - -

> (S - - - - - -

A1 - - - - - -

A2 - - - - - -

A3 - - - - - -

S1 - - - - - -

S2 - - - - - - -

S3 - - - - - - -

>eteran#an:

> (- : kelompok kontrol ne#ati% > ( : kelompok kontrol positi%

> (S : kelompok kontrol satelit

A1 : kelompok u&i 1)3 m#20 #

A2 : kelompok u&i 2) m#20 #

A3 : kelompok u&i 3)5 m#20 #S1 : kelompok satelit 1)3 m#20 #

S2 : kelompok satelit 2) m#20 #

S3 : kelompok satelit 3)5 m#20 #

- : ti"ak a"a perbe"aan bermakna

49


74/112

.ambar 4$3 6istopatolo#i hepar men*it yan# men#alami nekrosis (tan"a panah pewarnaan

6,) perbesaran 400<

>eteran#an:/$ >ontrol ne#ati% (./ 3

$ >ontrol positi% (/sam asetilsalisilat 1)3 m#20 #

$ >ontrol positi% satelit

D$ >elompok u&i /sam 2-(4-(klorometilben!oiloksiben!oat 1)3 m#20 #

,$ >elompok u&i /sam 2-(4-(klorometilben!oiloksiben!oat 2) m#20 #@$ >elompok u&i /sam 2-(4-(klorometilben!oiloksiben!oat 3)5 m#20 #

.$ >elompok satelit /sam 2-(4-(klorometilben!oiloksiben!oat 1)3 m#20 #

6$ >elompok satelit /sam 2-(4-(klorometilben!oiloksiben!oat 2) m#20 #

C$ >elompok satelit /sam 2-(4-(klorometilben!oiloksiben!oat 3)5 m#20 #

4$1$3$ Histo+atologi 4in&al

a"a penelitian ini men##unakan sampel 48 ekor men*it Swiss

webster &antan yan# "iba#i "alam 5 kelompok yan# ter"iri "ari 3 kelompok

kontrol yaitu kelompok kontrol ne

Skripsi subkronik

Documents

Transcript of Skripsi subkronik