EJH330203Doclofenacn harmful to thyroid function

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Egypt. J. Histol. Vol. 33, No. 2, June, 2010: 213 - 223

A Histological Study on the Effect of Diclofenac Sodium (Declophen)Administration on Thyroid Follicular Cells of Albino Rats

Nadia M. El-Rouby

Histology Department, Faculty of Medicine, Cairo University

ABSTRACTIntroduction: Diclofenac Sodium (declophen) is a nonsteroidal anti-inammatory drug recently categorized as thyroidantagonist.

Aim of the Work: To determine the histo-physiological changes that might occur in the thyroid follicular cells afterdeclophen administration and evaluate their reversibility.

Materials and Methods: Thirty adult male albino rats were randomly divided into three groups; Group I (Control

group), Group II received declophen (8 mg/kg /day) for one week then sacriced. Group III received declophen asgroup II and then sacriced one week after drug withdrawal. Blood samples were collected to estimate T3, T

4and TSH.

Thyroid glands were processed for microscopic examination. Mean follicular diameter and mean height of thyrocytes

were morphometerically evaluated and statistically analyzed.

Results: Declophen signicantly decreased T3level which did not return back to normal in group III. Histologically,

group II showed considerable light microscopic changes as focal distension of follicles that were lined with attened

epithelium. Their colloid revealed minimal peripheral vacuolations. Some follicles showed shedded epithelial lining.

Others appeared irregular with disrupted epithelium. That epithelium had irregular dark pyknotic nuclei and vacuolated

cytoplasm. Some follicles had apparently little colloid. Ultrastructural changes included dilated rER with electron lucid

material and many darkly stained lysosomes. Group III showed some changes compared with Control. Statistically, mean

follicular diameter of group II increased signicantly while mean epithelial height decreased signicantly compared to

Control. Group III revealed neither signicant increase in mean follicular diameter or decrease in epithelial height in

comparison with the control.

Conclusion: Declophen has toxic effect on the thyroid follicular cells which was incompletely recovered. So it shouldbe discontinued prior to evaluation of thyroid functions.

Original Article

Key Words:Declophen, follicular cells, thyroid gland,rats.

Corresponding Author:Nadia M. El-RoubyTel.:0111675532 E-mail: [email protected]

(ISSN: 1110 - 0559)

20 (1185-2010)

INTRODUCTION

Many factors including drugs can inuence thyroid

function in experimental animals and humans. Studies

in humans reported signicant effects of non steroidal

anti-inammatory drugs (NSAIDs) on thyroid tests,

which can lead to misinterpretation of the result and

inappropriate therapeutic decision1-3.

The role of NSAIDs in causing thyroid dysfunction

is quite often forgotten. These drugs might inuence

thyroid hormone homeostasis at any level from their

synthesis, secretion, and transport or end-organ action

as it might interfere with thyroid hormone binding

sites (competitive inhibition). They might also alter

the synthesis and secretion of thyrotropin (Thyroid

Stimulating Hormone: TSH)4,5. Some cases, however,

showed clinically apparent thyroid disease6.

Diclofenac Sodium (Declophen) is a potent NSAID.It has anti-rheumatic, anti-inammatory, analgesic

and anti-pyretic actions. It is commonly used as a pain

killer in many cases including rheumatoid arthritis,

dysmenorrhea, artheralgia, tooth ache and postoperative

pain7. Sometimes the drug may be used in high dosesdue

to severe agonizing pain or by mistake.

As NSAIDs are used more and more frequently in

human, it is important to know to what extent they can

inuence the thyroid gland. Reviewing the literature

showed that the inuence of NSAIDs, including

declophen, on the concentration of thyroid hormones

hasbeen established. However, there have been very few

previous studies demonstrating the effect of declophen

on the histological architecture of thyroid gland8. So

the objective of the present study was to evaluate the

declophen-induced alterations in the histological structure

and function of the thyroid follicular cells. It was also

aimed to evaluate the reversibility of such changes.


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Nadia M. El-Rouby

MATERIALS AND METHODS

A- Drug:

The drug used was Diclofenac Sodium (declophen),

presented as ampoules of 75 mg/3ml (Pharco

Pharmaceutical, Alexandria, Egypt). The dose used for

rats was 8 mg/kg body weight9. The drug was given daily

for a week by intramuscular (I.M) route. The control rats

were given physiological saline I.M. in the same volume

daily.

B- Animals:

Thirty adult male albino rats were used in this study.

Theywere obtained from Kaser El -Aini animal house.

Their weights ranged between 150-200 g. They were

kept under good hygienic conditions, fed ad libitum and

allowed free water supply. Rats were divided randomlyinto three equal groups as follows:

Group I: (Control Group):

Rats were given physiological saline daily ina similar

manner to other groups. Five rats were sacriced with

animals of group II and the other ve rats were sacriced

with animals of group III.

Group II: (Experimental Group):

Rats were given declophen as an I.M. daily dose of 8mg/kg body weight 9 for one week. After that week, the

rats were sacriced.

Group III: (Recovery Group):

Rats received declophen as in group II. The rats were

kept alive for another week without treatment. On the

15th day of the beginning of the experiment these rats

were sacriced.

Methods:

At the end of the experimental period, the animalswere sacriced under ether anaesthesia. Blood samples,

from all animals, were collected for hormonal assay.

Then, the thyroid gland of each rat was excised.

Hormonal Assay:

Hormonal assay was carried out at the Clinical

Pathology Department, Faculty of Medicine, Cairo

University, to determine the serum levels of T3, T

4and

TSH.

Histological Study:

1. For Light Microscopy: The thyroid tissues

were xed in 10% formol saline and processed

for parafn blocks. Sections of 5 micrometer

thickness were cut and stained with hematoxylin

and eosin (H&E).

2. For Transmission Electron Microscopy (TEM):Thyroid tissues were rinsed in phosphate buffer

(PH 7.4) then xed in 2.5% gluteraldehyde, post

xed in 1% osmium tetroxide andembedded in

epoxy resin. Semithin sections of 1 micrometer

thickness were cut on an LKB ultramicrotome

and stained with toluidine blue. Ultrathin

sections were stained with uranyl acetate and

lead citrate10 to be examined under Joel EM

100 S TEM using an accelerated voltage of 60

KV.

Morphometric Analysis of Both Thyroid Follicular

Diameter and Follicular Epithelium Height:

Leica Qwin 500 Ltd, image analysis system was used

to determine the diameter and the follicular epithelium

height of thyroid follicles. The two parameters were

measured in micrometers using lowpower (X 100) and

high power (X 400) magnication, respectively. The

internalfollicular diameters of 50 follicles, in 10 random

elds, of the thyroid gland of each rat of the different

groups were measured. They were measured on diagonal

axes. The mean of these two readings was then taken

as the internal diameter of the follicle. To measure the

epithelial height, 50follicles from each rat in 10 randomelds were chosen. The epithelial height was measured

at two points on thesame axis of each follicle. The mean

of these two readings was then taken as the epithelial

height. The meanvalue and Standard Deviation (SD) of

the data obtained for each group were calculated.

Statistical Analysis:

Statistical analysis was performed on IBM/PC

using SPSS (Version 11) / PC program. Comparison of

signicance between the different groups was made using

student T test11. Results were considered signicant

when probability (p) 0.05.

RESULTS

During the experiment, three rats died; two from the

experimental group (Group II) and one from the recovery

group (Group III).

Hormonal Assay:

It was clear that T3 was signicantly decreased in

both the experimental and recovery groups (P< 0.05)

compared to the control. On the other hand, there wasno signicant change of both T

4 and TSH (P >0.05)

compared to the control (Table 1 and Chart 1).


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A Histological Study on the Effect of Diclofenac Sodium (Declophen) Administration on Thyroid Follicular Cells of Albino Rats

Table 1:The mean values of T3in g/dL, T

4in g/dL and TSH in U/mL SD in different groups:

Item Control group Experimental group Recovery group

T3: Mean SD

T test3.9685 .09540

2.7100 .07071

* P1< 0.05

3.0990 .02767

* P2< 0.05

T4: Mean SD

T test2.6270 .02830

2.6150 .02550

P1 >0.05

2.6000 .02944

P2 >0.05

TSH: Mean SD

T test0.0118 0.00301

0.0137 0.00295

P1 >0.05

0.0120 .00267

P2 >0.05

P1 = between the experimental group and control group.

P2= between the recovery group and control group.

* Signicant P value.

Histological Results:

Group I (Control Group): The thyroid gland ofcontrol rats was composed of follicles lined with a

single layer of cuboidal follicular cells, and lled with

acidophilic homogenous colloid having peripheral

vacuolations (Figs. 1-A and B). The thyroid follicles

were surrounded by vascular connective tissue stroma

(Figs. 1-A and 2-A).The follicular cells had vesicular

nuclei and prominent nucleoli (Fig. 2-A). Electron

microscopy revealed that the follicular cells hadeuchromatic nuclei, rough endoplasmic reticulum and

mitochondria. The apical cytoplasm revealed secretory

vesicles. The colloid showed peripheral vacuolations in

the form of electronlucid areas (Fig. 2-B).

Group II (Experimental group): Examinationof the thyroid gland of rats of the experimental group

revealed focal markedly distended thyroid follicles.

These follicles were lined mostlywith attened epithelial

cells that had attened nuclei. Their colloid showed

nearly absent peripheral vacuolations (Fig. 3-A). Some

follicles revealed shedded cells. The interstitial tissue haddilated blood vessels (Fig. 3-B). The thyroids of some

animals revealed focal involuted follicles with minimal

Chart 1:The mean value of T3, T

4& TSH levels.

was interrupted (Fig. 4-B). The lining follicular cellsof

the damaged follicles had darkly stained irregular and

pyknoticnuclei. The cytoplasm of the affected thyrocytes

was vacuolated (Figs. 5-A and B). The follicles showed

variable density of colloid staining. Mast cells werefrequently seen in the interstitial tissue close to blood

vessels (Fig. 6). Electron microscopy revealed that the

nuclei of the affected follicular cells appeared indented

and hetrochromatic with dilatation of the peri-nuclear

space. The cisternae of rER were dilated and contained

amorphous lightly stained material (Figs. 7 and 8).

The cytoplasm showed many darkly stained lysosomes

and prominent Golgi complex (Fig. 9). The distended

follicles were lined with attened thyrocytes that had at

nuclei (Fig. 10).

Group III (Recovery Group): The thyroid folliclesof rats of thisgroup started to regain their activity andnormal appearance but patchy in distribution. These

follicles were lined with cubical epithelium and showed

peripheral vacuolations of their colloid content. Many

distended follicles were still seen. These follicles

were lined with attened thyrocytes. Their colloid had

minimal peripheral vacuolations. Also, involuted and

distorted follicles persisted (Fig. 11). The follicular cells

had vesicularnuclei. Some mast cells with darkly stained

granules were seen in the surrounding connective tissue

beside the blood vessels (Fig.12). Electron microscopy

revealed that the follicular cells appeared more or less

normal compared with the control group. They hadmore or less regular euchromatic nuclei with prominent

nucleoli. The cytoplasm had more or less normal rER

cisternae but many vacuoles and many darkly stained

lysosomes were still seen in some follicular cells

(Figs. 13 and 14). Some follicular cells showed sings of

regeneration as they were binucleated (Fig. 15).

Morphometric Study and Statistical Analysis:

The mean diameter of thyroid follicles of rats of the

experimental group was signicantly increased (p1< 0.05)

compared to thecontrol group while the mean folliculardiameter of thyroid folliclesof the recovery group was

insignicantly increased (p 2 >0.05) incomparison with


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Nadia M. El-Rouby

Table 2: The mean follicular diameter in m SD of thyroid follicles of different animal groups:

Control group Experimental group Recovery group

Mean follicular diameter in m

T test35.79.6

51.913

* P1< 0.05

36.69.9

P2>0.05




Chart 2: The mean follicular diameter of thyroid follicles of the different groups.

The mean epithelial height of thyroid follicles of

the experimental group was signicantly decreased(p1< 0.05) compared to the control group while the mean

Table 3:The mean value of epithelial height of thyroid follicles in m SD in different groups:

Control group Experimental group Recovery group

Mean epithelial height in m

T test9.21.6

6.81.4

* P1< 0.05

8.91.9

P2>0.05




epithelial height of the recovery group was insignicantly

decreased ( p2 >0.05) compared with the control group(Table 3 and Chart 3).


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Fig. 1: Photomicrographs of sections in the thyroid gland of a control rat(group I) showing:

a. Normal thyroid follicles lined with simple cuboidal epithelium and

lled with colloid (C). Note blood vessels (BV) in the surrounding

connective tissue stroma. H&E X 200.

b. The colloid (C) has peripheral vacuolations (V). H & E X 400.

Fig. 2: Photomicrographs of:a. Semithin section in the thyroid gland of a control rat. It shows that

the follicles are of variable sizes and lined with cuboidal follicular

cells that have vesicular nuclei (N). The follicles are lled with

colloid (C). Note that the stroma has many blood capillaries.

Toluidine blue X 1000.

b. TEM section of a control rat thyroid showing a part of thyrocyte.

The colloid (C) shows two electron lucid areas (V) of peripheral

colloid vaculations. Cisternae of RER and mitochondria (m) are

scattered throughout the cytoplasm. Many secretory vesicles

(S) in the apical cytoplasm and part of the nucleus (N) are seen.

Orig mag X 2000.

Fig. 3: Photomicrographs of sections in the thyroid gland of rats from theexperimental group (Group II):

a. Reveals markedly distended thyroid follicles. They are lined mainly

by at cells with at nuclei (arrow) and few low cuboidal cells with

apparently rounded nuclei (arrow heads). The colloid (C) shows

apparently no peripheral vacuolations. H&E X 400.

b. Shows that some follicles have shedded epithelial lining (*). The

thyrocytes of most of the follicles have vacuolated cytoplasm

(arrow). Note the dilated blood vessel (b.v). H&E X 400.

Fig. 4: Photomicrographs of sections in the thyroid gland of rats from theexperimental group (Group II):

a. Shows thyroid follicles of variable activity as some follicles are

markedly distended (1) and other follicles appear involuted (2).

These follicles have minimal amount of colloid. H&E X 200.

b. Reveals a follicle with interrupted follicular wall (arrow). The

adjacent follicles showing thyrocytes with vacuolated cytoplasm

(curved arrow). H&E X 400.


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Fig. 5: Photomicrographs of semithin sections in the thyroid gland of ratsfrom the experimental group (Group II):

a. Shows that the follicles have vacuolated colloid (C). The thyrocytes

have vacuolated cytoplasm (V) and indented darkly stained

pyknotic nuclei (arrow). Toluidine blue X 1000.

b. Shows that the destroyed follicles reveal shedded cells into

their lumina (encircled).The nuclei of the shedded cells appearirregular and darkly stained. The thyrocytes reveal vacuolated

cytoplasm (V). Toluidine blue X 1000.

Fig. 6: A Photomicrograph of semithin section in the thyroid gland of arat from the experimental group (group II). It shows a distorted follicle

with shedded cells (S) into its vacuolated colloid (C). These shedded cells

have irregular indented darkly stained nuclei. The colloid (C) reveals

variable density of staining. The thyrocytes show vacuolated cytoplasm

(V). The surrounding stroma is very vascular. Mast cell (M) is seen close

to interstitial blood vessel. Toluidine blue X 1000.

Fig. 7: A Photomicrograph of TEM section showing two thyrocytes oftwo adjacent follicles of a rat from the experimental group, the upper

left thyrocyte is of a damaged follicle showing dilated rER (d rER). Itsnucleus is hetrochromatic and indented (arrows). The lower thyrocyte is

related to more or less normal follicle with normal cisternae of rER but

with apparently more darkly stained lysosome (L) Note the projecting

Fig. 8: A Photomicrograph of TEM section showing two thyrocytesof a thyroid follicle of a rat from the experimental group. It shows

dilated cisternae of rER (d rER) with amorphous material (*). The

nuclei (N) appear indented with dilated peri-nuclear space (arrows).

The nuclei have prominent nucleoli (Nu) and hetrochromatin (h).

Original mag X 6000.

Fig. 9: A Photomicrograph of TEM section of a thyrocyte from a ratof the experimental group reveals apical microvilli (Mv) projecting into

the lumen that has colloid (C). Many darkly stained lysosomes (L) are

seen. The cytoplasm shows prominent Golgi complex (G) and cisternae

of rER. Original mag X 8000.

Fig. 10: A Photomicrograph of TEM section of the thyroid gland from arat of the experimental group (group II). It shows two follicular cells withattened nuclei. The nuclei have hetrochromatin. The cytoplasm shows

darkly stained lysosomes (L). The colloid (C) is apparently homogenous.


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Fig. 11:A photomicrograph of thyroid gland of a rat from the recoverygroup (Group III). It reveals some recovered follicles. These follicles

show vacuolated colloid (V). Other follicles appear distended with

colloid (C) and lined with at epithelial cells. Note that there are still

some distorted follicles (D). A forth group of involuted (I) follicles areseen. H&E X 200.

Fig. 12: A photomicrograph of semithin section in the thyroid gland ofa rat from the recovery group (Group III). It shows that the follicles are

lled with homogenous colloid (C) and lined with cuboidal cells that

have vesicular rounded nuclei (curved arrows) and some low cubical

cells with attened nuclei (straight arrows). Some mast cells (m) are seen

in the stroma. Toluidine blue X 1000.

Fig. 13:A photomicrograph of TEM section of the thyroid gland of a

rat from the recovery group (group III). It shows a follicular cell withmore or less euchromatic nucleus (N) and prominent nucleolus (nu). The

cytoplasm reveals more or less normal cisternae of rER, many vacuoles

(V) and some electron dense lysosomes (L) The lumen shows colloid (C)

Fig. 14: A photomicrograph of TEM section of the thyroid glandfrom a rat of the recovery group (Group III) showing two thyrocytes

with more or less normal rER. Their nuclei appear euchromatic but

with some irregularity. The cytoplasm reveals many vacuoles (V) and

mitochondria (M). Many electron dense lysosomes (L) are observed.Original mag X 6000.

Fig. 15:A photomicrograph of TEM section of a thyrocyte from a ratof the recovery group (Group III) showing two nuclei with prominent

nucleoli. The cytoplasm shows vacuoles (V) and electron dense

lysosomes (L). Original mag X 6000.

DISCUSSION

There is a list of medications that alter thyroid

function tests. This list include furosemide, NSAIDs

(salicylate, diclofenac sodium), heparin, amiodarone andiodinated contrast media12. As NSAIDs are commonly

used drugs so thyroid dysfunction is a potentially

forgotten complication of NSAIDs therapy5.

In the current study, declophen was administered to

rats of group II daily for one week to evaluate its effect

on the structure and function of the thyroid gland. Group

III received declophen for the same duration as group II

and this was followed by another week without treatment

for recovery to asses the reversibility of these changes.

Death of rats that occurred during the experiment was

most probably due to liver and/or kidney affection9,13

.

The present study reinforced the previous recorded


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Nadia M. El-Rouby

including diclofenac sodiumcould lower serum T3while

T4 and TSH were not affected. This might be because

NSAIDs block peripheral (tissue) conversion of T4 to

T3and produce a low concentration of T

3as most of T

3

is produced from peripheral conversion of T4 to T

3by

enzyme 5- deiodinase. The levels of T4and TSH were not

affected. This was most probably because T4is strongly

bound to plasma proteins and its biological half life is

long(6-7 days) so subsequently TSH remained without

change17. Another cause for insignicant change in T4

level could be because the thyroid gland is a unique

gland that stores its hormones extracellular in an amount

sufcient for weeks18. NSAIDs including declophen

affected the tests of the thyroid gland through alteration

in the synthesis, transport, and metabolism of thyroid

hormones1,3,5,16. This was proved by both light and

electron microscopic ndings. At the light microscopic

level; some follicles showed degenerative changes in the

form of shedded degenerated thyrocytes. The thyrocytesof more affected follicles had vacuolated cytoplasm and

small, irregular dark pyknotic nuclei. At the level of TEM;

the nuclei of thyrocytes were indented, heterochromatic

with widening of the peri-nuclear space. This might be

attributed to its connection to dilated cisternae of rER. The

rER cisternae were dilated and had intra-luminal electron

lucid material of storedunprocessed protein. Also there

was apparent increase in dark stainedlysosomes.

Light microscopic examination of thyroid glands

of rats of the experimental group (Group II) revealed

marked distortion of follicularstructure. Some folliclesappeared distended and lined by at follicular cells

due to increased their colloid content that had minimal

peripheral vacuolations denoting hypoactivity of these

follicles. Other follicles appeared small in size with

apparently little colloid. These follicles mightbe newly

formed, collapsed or involuted follicles. A third groupof

follicles had shedded epithelial cells. These changes could

be attributed to cellular distension with accumulated

colloid which resulted in cellular disruption and collapse

with subsequent collapse of the follicles. The degenerated

cells had dark stained nuclei and vacuolated cytoplasm.

These ndings were recorded in cases of thyroiditis19.

Many mast cells were observed frequently in the inter-follicular connective tissue beside blood vessels. This

nding might be due to an allergic reaction occurred in

the thyroid gland as these mast cells secrete cytokines

and chemical mediators responsible for allergic reaction.

This allergic reaction might be because NSAIDs altered

plasma proteins. These NSAIDs- altered proteins could

become antigenic. By time these antigens would become

immunogens20. Former studies reported that mast cells

participate in the process of thyroid hormone secretion

and in thyroid gland activity. Mast cells might mediate

the action of TSH on follicular cells. TSH has been

shown to promote the release of serotonin from thyroidmast cells. Serotonin activates thyroid follicular cells

by enhancing them to extend pseudopodia and engulf

Some follicles revealed variable staining density of

colloid. This might indicatevariable follicular activities.

This nding was supported by Wollman et al.23 who

mentioned that density of staining of the accumulated

colloid varied from follicle to follicle and correlated the

staining reaction of the colloid with the activity of the

follicle. Other follicles had vacuolated colloid which

might be due to defect in pinocytosis of follicular cell.

Thyrocytes of the more affected follicles revealed

pyknotic nuclei and vacuolated cytoplasm. This could

explain the lowered level of thyroid hormone (T3)14.

Ultrastructurally, the follicular cells of the damaged

follicles revealed widening of the peri-nuclear space,

irregularity and indentationof the nuclei with chromatin

condensation, dilatation of rER withintra-luminal electron

lucid material, apparently increased darkly stained

lysosomes and prominent Golgi complex. Widening of

the peri-nuclear spacemight be due to shrinkage of thenuclei due tothe toxic effect of declophen. Also, this might

be attributed to its connection to dilated cisternae of rER.

The pyknosisof the nuclei and condensation of chromatin

observed in thyrocytes of declophen treated rats have been

also observed in other tissues as rat liver cells exposed

to NSAIDs24. These changes could be degenerative

changes. Declophen might induce these degenerative

changes either directly or indirectly. This nding was

in agreement with Boelsterli25and Moorthy et al.26who

observed that declophen caused injury of liver cells and

they referred this to immune mediated response. Many

darkly stained lysosomes were seen in the cytoplasm ofthyrocytes of rats administered declophen. The apparent

increased number of lysosomes could be explained by

the accumulation of highly iodinated thyroglobulin that

was resistant to proteolysis27. Marked dilatation of rER

was an evidence of disturbed protein synthesis. This

dilatation could be due to retention of aberrant protein

within their cisternae. Therefore, this mightbe a form of

rER storage disease. This protein could not be processed,

folded and transported to appropriate sites. Disruption in

protein production might prevent synthesis of apoptosis

inhibitors and/or loss of essential proteins involved in

cellular homeostasis leading to cellular degeneration28,29.

The dilated rER might bethe cause of nuclear indentationand irregularity as the dilatedrER compressed the nucleus

causing its indentation and irregularity.

Using light microscopy, the thyroid gland of the

recovery group revealed that the gland needed more

time to return back to normal structure. The thyroid

follicles revealed patchy recovery. Some follicles were

still large in diameter and distended with colloid with

minimal peripheral vacuolations which indicated hypo-

activity. Other follicles were smaller in diameter, lined

with cuboidal cells mainly and their colloid had some

peripheral vacuolations i.e. these follicles regain theiractivity.


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appeared more or less normal with slightly indented

euchromatic nuclei and prominent nucleoli. The

cytoplasmic organelles were more or less normal in

appearance except for the presence of apparently more

darkly stained lysosomes. Some thyrocytes revealed

variable sized vacuoles in their cytoplasm. This indicated

that rat thyroid needed more time to recover completely.

Morphometeric study of thyroid follicles of rats of

theexperimental group (Group II) revealed statistically

signicant increase in the mean follicular diameter

and statistically signicant decrease in the mean

epithelial height in comparison with the control group

(Group I) which denoted hypoactivity of the gland.

This was proved histologicaly as many follicles were

markedly distended with colloid and linedmainly with

at cells. The colloid was homogenous acidophilic and

showed minimal peripheral vacuolations. The less active

follicles of the thyroid gland were distended by storedcolloid and the lining cells appear attened against the

follicular basement membrane17,30.

One week after declophen withdrawal (recovery

group; group III), the morphometeric analysis of the

thyroid follicles showed insignicant increase in the

mean follicular diameter of thyroid follicles and also

insignicant decrease in the epithelial height of the lining

follicular cellsin comparison to the control group. This

could be attributed to starting reactivity of the thyroid

gland as a result of recovery from the toxic effect of

declophen and elimination of harmful waste productsfrom the body.

CONCLUSION

Declophen, a cytotoxic drug, induced variable

structural and functional alterations in the thyroid

follicular cells of adult male albino rats. These alterations

were incompletely recovered. So, it is advisable to avoid

using declophen as rst pain killer and if it is used, thyroid

function tests results should be interpreted cautiously

in patients on declophen therapy. The drug should be

discontinued prior to evaluation of thyroid function.

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EJH330203Doclofenacn harmful to thyroid function

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