Zinc and Wound Healing

8/3/2019 Zinc and Wound Healing

1/6

DAYS

EXC ISED W OUNDT I, D AY ZERO TO HEAL IN G

Z IN C PA IR FEDD EF IC IE NT CONTRO L

P < .001

8

7

6

5

4

3

2

THERMA L BURNT 1/2 DAY 6 TO 19 OR 23

Z IN C PA IR FEDDEF IC IENT CON TROL

D AY 6 TO 23

P< 0 01

51 4

TO E AM FhI (AN .JoLRN ;5I. O F (L IxIc .sL Nu iiu rio s\1. 23 , N . 5 ,May , 1970 , pp 514-519

Vru U d in (-I .

O rig in al C om m unica tion s

Z in c and W ound H ea lin gE ffects o f Z inc D efic iency and Z inc Supp lem en ta tion1 2

HAROLD H . SANDSTEAD ,3 M .D ., VER NE C . LANIE R , JR .,4 M .D ., GL ENN H .SHEPHARD , 5 M.D. , AN D DAVID D. G ILL .E 5PIE ,0 B .A .

Z INC , AN ESSENT IA L NUTR iENT fo r h ig heran imals an d! p lan ts, has a t leas t tw o

b io log ica l fu nc tion s: a) it is a com ponen tl) 11 t o f severa l m eta lloenzym es and b ) itp lays an incom ple tely un !e rstoo d ro le innuc le ic acid! an(! pro te in m e tai)ohsm (1 ) ,w h ich m ay be ind!epend!en t o f its m eta llo -enzym e func tion . I ts req u irem en t fo r d Ie -ox y tib onuc le ic ac id sy n thesis in rat live r(2 , 3 ) and! fo r the u tiliza tion of am ino acids(1 ) by the ra t a re exam ples o f th is la tte rfunc tion . P erhaps , as a con sequen ce of itsro le in these m etabo lic p rocesses, z inc defi-c iency resu lts in a d ecreased ! tens ilestreng th of hea ling su rg ica l inc isions in thesk in of ra ts (5 ) an d de lays hea ling of b o-v ine sk ill (6 ) .

T he prac tica l im plica tion s of the po ten -tia l use fu ln ess o f z inc in th e treatm en to f pa tien ts w ith poo r wound hea l ingpro lnp te (! tiiis study .

MATER IA lS AND M ETHODS

W eanhing fem ale an d 150-g m ale Sp rague-1 )aw lcy rats w ere fed a pu rified . 20% pro te in ,

From t e 1) is is ion o f No tnt 1011 and Dep a r tmen to f Su rgciv , Vanderb i l t tniversitv Schoo l o f M ed i-c ine . Nashvil le . Tenne s s e e 37203.

S uppo rted b N utr itio n Found ation (;ran t 97 ,Lllite(l Health F oun(la tio n ( ;ran t 69-9-42 , an d U .S .Public H ea lth Se r ice (ran t AM 03411 .

. s istan t P ro fe ssor of Nutritio n and A ssis tan tP ro fe ssor o f M edicine . A ss is tan t R es ident inS urg ery . C hie f R es iden t in S urgery . 11 Resea rch. s is tan t to 1 )r. S an ds te ad .

F ic . 1 . /.in c-(lehc ien t an d p air-fe(l co ntro l ratsarc com pared for ra te of w ound closure fo llow in gexcis ion o f an area o f sk in or the rm a l b urn . Th e(liffer en ces b etw een the means are high ly s ign i l i c ant .

sp ray e! egg white , b io t in -cnriched d iet con -taillilig


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Day 0-5 or

Ti /? K T i? KDe f i c i e n t

2.332.665.33

Day 0 to h ea lin g o f th e con tro l

Co n t r o l

2.332.332 . 6 6

Pa ir s

l2 3455e

678

1011121 31415l6 c

Def i c i ent Co n t r o l

0 .258 0 . 2 5 80 2 6 1 0 . 2 5 80 . 1 3 2 0 . 2 6 1

0 . 2 6 1 0 . 2 7 80 . 3 4 6 0 . 4 6 2

0 . 3 9 0 0 . 3 9 00 . 3 4 6 0 . 3 4 60 . 3 0 8 0 . 3 9 00 . 3 0 8 0 . 3 9 60 . 3 4 6 0 . 2 6 50 . 2 8 8 0 . 3 8 90 . 3 8 5 0 . 4 3 30 . 1 7 3 0 . 3 8 50 . 2 8 8 0.4080 . 3 8 5 0.408

2 . 6 6 2.492 . 5 0 1 . 5 0

1 . 7 5 1 . 7 52.00 2 . 0 02 . 2 5 1 . 7 52 . 2 5 1 . 7 52.00 2 . 6 22.40 1 . 7 81.80 1.604.00 1.802.40 1.701 . 8 0 1 . 7 0

De f i c i e n t

6.498.66

Pos it ives l o p e d6.337 . 7 54 . 2 52 . 8 83.753 . 7 53 . 7 54 . 7 53.603.405 . 2 03.603.40

Co n t r o l

5.332.663.66

4.333.002 . 5 03.132 . 5 03 . 0 02 5 03 . 5 02 . 9 93.102 . 7 02.652 . 9 5

I)e Iicient

0 . 1 0 70 0 9 0

P o s i t i v es l o p e

0.1090 . 0 8 90. 1630 . 2 4 10 . 1 5 40 . 1 5 40 . 1 5 40 . 1 4 50 . 1 9 20 . 2 0 40 . 1 3 30 . 1 9 20 . 2 0 4

Con t r c l

0.1320 . 2 6 10. 188

0. 1 6()0 . 2 3 10.3460 . 2 2 20.3460.2310.3460. 1980 . 2 3 20 . 2 2 40 . 2 5 70 . 2 6 10.233

P


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a L, .73 1 /: 516 Sandstead et al .

F r o . 2 . E f f e c t of zinc def i ciency on closure of surgical w oundsn t h e i ntegument of the rat. The zi nc-def i -cient rat, XIIa, is c o m p a r e d wi t h i t s p a i r - f e d c o n t r o l , .VIIb, and an a d l i b i t u m e Ol l t r o l a t i n t e r v a l s fo l l owingwounding. . \ l l w ounds w ere the same size w hen f i rs t e x c i s e d .

i i th im i it ppL I f or dcternm ination ofil e half - t imeof wound (osure. I he f racti onal rate of cl osurewa s thc ii calculated a n ( ! t i me signi f i cance of t i l edifference i ) e t w e e i i the means dictermined.

lo asertain t ime coi i tr i l )uti on of zi nc s u p p l e .melmta tion to teimsi le strength of I l cal i l i g woundsi l l norimma! rats, 200-g rats w ere fed Purina ratchow, g i v e n tap w ater, and maintained ing a l v a i mi l e ( ! c a g e s . F i l e \ we r e d i v i d e d i n t o p a i r si i i c l o i l e me mb e r o f e a c h wa s i n j e c t e dw i t h 400

g l ine t ia i1 Re r z i n c h a d i ) e e n s u p p l e -nmente(! f or 7 days, 4-cmmm incisioims w ere placet! int i l e t i o t s a l i n t e g u n me n t . l i me wounds were closet!b y i n t e r r t l i ) t e ( ! s t i t u r e s a n d t i me t e n s i l e s t r e n g t ht l e t e r n mi n e d 6 a n d 1 2 d a y s i ) y t i l el l l et imo(! of Savhov a l l ( I Du n mp h v ( 9 ) . T o d e -ternl i ime ti le ef f ect of zinc treatment on w oundclosure of a normal rat, 16 adul t maleswere

div i ( ie(! into pai l s, houset! and fed s ( iescrii)eda I )Ove, a 11(1 trea ted! w ith preim tei 1 zi nc. l )upl i -cate areas of sk i im were excised f rom cati but-tot k . l ime rate of closure w as (i eter nm ii me(! asc! ecri bcd ai )ove.

R l - :s tLTsZinc deficiency resul ted in a delayed

closure of time surgi cal l y prot l tl ce(! wO tln(! s(Table i ) (Fi gs. I and 2), w hich w as im igh lysignificant (P < 0.001) w hen related to timetim e of heal i ng of time control animals.T ime di f f erences betw eeim time rates ofw oui x ! cl osure of time tw o groups of ani -mal s w ere l ess stri k ing (!uming ti le ini t ialperi od! of observati on (P < 0.01). I nspec-tion of time (i ata show s that tw o def i cient


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40 0

30 0

20 0

00 -

CONTRO L ZINCSUPPLE -MENTED

..# { 14 9} # { 1 49}

# { 1 4 9 }# {1 49 }# {14 9}. -

.-.-.. # {1 4 9 }# { 1 4 9 }# { 1 4 9 }

# { 1 4 9 }

#{ 149 } # { 1 49}

N.S.

U)

zI1-0zwI-U)

w-JU)zEdI-

PA IR FED Z INCCONTROL DEF IC IENT

#{149}

# {1 4 9 }# { 1 4 9 }#{149}r# { 1 49} # { 14 9}

#{149} $

# {1 4 9 }

P < .001

TA BLE 11Effect o f zinc defic iency on rate o f c losure o f

TI! K

P


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I -

518 Sandstead e t a !.

FIG . 4 Conlmectlve ti ssue strain of 12-clay postoperati ve surgical incisions i n the dorsal integulnent of zinc-deficlelst a n d p a i r - f e d c o n t r o l rate. The zinc def i ci ent w ound, oemhe l e f t , has few er f ibroblasts i n the area ofh e a l i ng a n d d e c r e a s e d densi ty of col lagen compared to the pai r-f ed controlound o n t h e r i g h t .

teI ls i le strengtim of w oti nds om imasteim do-sure. Prev i ously w e f ound! that tensi l esti eimgtim of imeal i img inci sio lms i s decreaset!b s di etary def i ci ency of zi nc (5) . Caloriel estri ctio lm Stl i )SeqtiC l l t to lee( ! ing dit!not t ! elay w oul id cl osure.

A ! tl i oti gim time explaimation foi the im -1 ir imment of wount! closure and! tensilestreimgtim i s as et unknow n, w e suspecttimat time answ er may i)e melatet! to zi nc si -o le il l nucleic acid aimd protei n sy ntimesi s.I - i i stol ogi c exanm i Imati on of 12-day postop-c i i t ive incisions (F i g. -1) f rom zinc-t! ef i -cient amd pai r- f ed con trol rats simow s fewerl i brobiasts in t ime region of time heal i ngi lmcisi ol l of t ime zinc-deprived aim imal and

t!etreasct! d!el ls it ) of time col l agen. 1lme sub-j ecti velmess of tlmese observ ati ons obv iousl ymakes t imeim i tel l tat i ve. 1imey are, imow ever,consi stent w i th time di f f erences in tensi l estrengtim betw een time tw o groups of a imi-mal s (5).

im is study nei timer coim f i rmmmsno r defi-ni tel y i -ef utes time impressions of Sti ai n et;ii. (10, I l ) and Hu sa in (12) that / ine w i l l im -pro se w ount! heal i lmg in nonzinc-d! cf ici entint! iv idua!s. ()ur negat ive observationssupport t ime f i ndings of O R iai n et al .13) ,w ho mel)t)rted t imat zi nc suppl em entati on ofnormal rats (! i d not i ncrease time tensi l estrength of 7-day i )ostoi )eri i t iv e wounds.I ..Jlm lor tt i nately O R iai n Ct a! . ( l i d! not meas-


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Zinc and Wound Healing 51 9ui-e tens ile strength 12 dlay s postoperative .The ir findings are , therefo re , not entire lycompar able w ith our s (Fig . 3 ). In ourstudies of the effec t of zinc def iciency ontens ile s trength w e found significant dif-ferences betw een the str ength of zinc defi-diem and I )aim-fed! contr ol w ounds after 12day s, w hereas the d!ifler ences wer e not sig-ni fican thy different 7 day s postoperativ e .We, ther efor e, measur ed tensile str engthof wounds of normal zinc-supplenmentedanimals 1 2 day s postoperativ e.

It seems unlike ly to us that treatment ofa normal int!iv idual w ith zinc w ill im - se ile ahing . We stiggest that ind!iv iduals(men or animals) that demonstr ate im-proved healing subsequent to zinc them--apy ar e r elatively zinc de fic ient and havebeen rece iv iimg a (lie t marg inal inincprio r to the institutio n of therapy . It mayi)e that local tis sue i-equirements for z incaie increased! during healing and that in-adequate d!ie tary intake beco ines cruc ialin this situation.

SU M M A R Y

The r ate of closur e of d!efects inhe in-tegum ent (stii-g ical or thermal) and thetensile streng th o f healing w ounds aree-creased! by z inc deficiency in the i-at.

Zinc supplem entatio n o f no rmal ratsw ill not improv e the rate of c losure or thetensile s trength of w ounds inhe integu-ment.

The a u t h o r s t l ma n k Dr . \ V i l l i a m J. Darbyand D r. H. W illiam S cott for their comnments aimdsuggest ions.

REFERENCES1. UNDERWOOD , E. J. Zinc . l im: T i-ac e E lem en ts in

H um an an d A n im al N u tr itio n . N ew York:Academic, 19 62 , p. 1 57 .2. FuJI0KA , M ., AN D I . LIEBERMAN. A Z im require-ment for synthes is of deoxyribonucle ic acid byr at liver . J . B io l. C / t e r n . 2 3 9 : 1 1 6 4 , 1 9 6 4 .

3. SANDSTEAD , H . H ., -SND R . A. RiN !uol. Impair-me imt of deo xsriboimucle ic ac i(l synthes is bydie tary zinc de fic iency jim timeat. J. Ce l l P i i y s i o l .7 3 : 8 1 , 1 9 6 9 .

4. BU CHA NA N , P. J., AN I ) J. M . H su. O xidation of#{176}C- lab1ed anmiimo ac ids iim z iimc deficient rats .h de ra t ion P roc . 2 8: 762 . 1969.

5 . .S -s sos ii n, H . i-I., SN O C . H . SIiEen.sRn. Effectof / i imc defic iency on time teimsile str ength (ifIm ealiimg surg ical iimcisio ims jim time iim tcgunme imt oftime r at. P io c . S ac . l! x l. Th a i. M ed . 12 8: 687 ,1968 .

6. M illER , W . J., J. D . MORToN , \V . J. Pi i r s ANI)C . M . C iiF ioN . E ffect of z inc de fic iency andr e s t r i c t c( l f ee d i i mg o m wound heahiilg in bovine.Proc . S oc . E xp tl. itio l. M ed . 1 1 8 : 4 2 7 , 1 9 6 5 .

7 . Pr-s o W . N ., M . REICH , H. FRA N KND L .Ss1SMvr. E ffect of dietary iroim level oimutiro im leve ls and iron al)sorptio lm ji m tim e rat. /.V u t r . 92: 3 3 , 1967 .

8. FORBES , R. M ., AN D M . Y0I IE. Z ii mc re qu ire me ntand balance studie s in the r at. I . Nii tr . 70 : 53 ,1960 .

9. S sv iov , E. D ., . -sNI) J. E. D usiiiiv . Mec iman ismsof w ouimd imealing . New Eng i. 1 . M ed . 2 5 0 : 1 0 6 2 ,1954 .

10. ST RA I N , W . H ., A .M . D urrox , H. B . HEYR .&NDC . H . R AM sEY . E xper imental sttidies oim the ac-celeratioim of bur im antI wouimd healing. Un i v .Ro che ste r R ep t . Rochester, Ne w Y ork, 1 95 3 .

11. Por s, \V . H ., J. H . H EN JEL , C . G. RO B ANDW . H . S TRA I N . Accelerat ion of healing witim zincsulfate. Ann . Su r g . 165: 432, 1967.

12 . H USA IN , S. L . O ral zinc sulfate iim leg ulcers.I .ancet 1: 1069, 1969.

13. OR i-ux, S., H .J. COPENH AGEN AND J. S. CAL -SIAN. T ime effect of zinc sulphate on the healingof incised wounds iim rats.B,i t . J . P la stic Su rg .21: 240, 1968.

Zinc and Wound Healing

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