Combined Effects of Methionine and Kiwi Fruit on Paracetamol Induced Liver Injury

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1 World Journl of Medil Sienes 9 (1): 01-07, 2013 ISSN IDOSI Pulitions, 2013 DOI: /idosi.wjms Comined Effets of Methionine nd Kiwi Fruit on Pretmol Indued Liver Injury Rsh M. Ngi Deprtment of Home Eonomis, Fulty of Speifi Edution, Mnsour University, Egypt Astrt: In the present study, the effets of methionine nd kiwi fruit powder on pretmol indued liver dmge were evluted. Forty dult mle of white lino rts (Wistr rts strin) were rndomly lssified into five groups (8 rts eh). The first group kept s ontrol negtive. The rest rts were dministered pretmol to indue liver injury nd lssified into ontrol positive nd treted groups whih were methionine, kiwi powder nd kiwi powder with methionine groups. Liver sprtte nd lnine minotrnsferse (AST, ALT) tivity, lkline phosphtse (ALP) nd gmm glutmyle trnsferse ( GT) enzymes s well s totl iliruin, totl protein, lumin nd gloulin were determined in serum. Liver lipids prmeters (holesterol, totl lipids, triglyeride nd glyogen), Liver ntioxidnt enzymes (superoxide dismutse, SOD, glutthione peroxidse, GPX, glutthione S-trnsferse, GST nd tlse) were estimted. Pretmol dministrtion showed signifint derese in nutritionl results; liver ntioxidnt enzymes; liver triglyeride nd liver glyogen ut showed signifint inrese in liver nd renl funtion prmeters enzymes nd MDA s shown in ontrol positive group. Liver injured rts groups whih fed diet ontins methionine or kiwi powder or methionine with kiwi powder hd signifint inrese in ody weight gin, food intke nd feed effiieny rtio (FER) ompred to rts of ontrol positive group. Consumption of methionine with kiwi powder showed signifint improves of liver funtion enzymes, liver ntioxidnt enzymes nd liver lipid pttern ompred to rts of ontrol positive group tht is my e due to its ugmenting endogenous ntioxidnt mehnisms. Key words: Kiwi fruit Methionine Pretmol Rts INTRODUCTION Liver is the key orgn of metolism, exretion nd detoxifition of environmentl toxints. Liver dmge is ssoited with distortion of severl metoli funtions. Numerous mediinl plnts nd their formultions re used for liver disorders [1]. Aetminophen (Pretmol) is widely used ntipyreti nd nlgesi drug whih is sfe in therpeuti doses ut n use ftl hepti dmge in humn nd nimls t higher toxi doses. An oxidtion produt o f etminophen is N-etyl p-enzoquinomine whih inds sulphydryl groups of proteins resulting in ell nerosis nd lipid peroxidtion indued y derese in glutthione in the liver s the use of heptotoxiity. Hepti ells pper to prtiipte in vriety of enzymti metoli tivities nd etminophen produed mrked liver dmge [2]. Epidemiologil studies hve indited possile reltionships etween fruits nd vegetle rih diet nd reduing the risk of hroni diseses, espeilly oronry hert disese, dietes mellitus nd some mlignnies [3]. The kiwifruit (Atinidi deliios) is smll fruit pproximtely 3 inhes long nd hs rown hiry peel with green flesh nd white pulp in the enter with mny tiny lk edile seeds. Its green flesh is lmost remy in onsisteny with n invigorting tste reminisent of strwerries, melons nd nns, yet with its own unique sweet flvor. Kiwifruit ontins numerous phytonutrients s well s well known vitmins nd minerls tht promote helth [4]. Kiwi fruit hs inredile helth enefits. Studies reveled tht diseses like sthm ough nd dietes hve shown positive improvements with the dily onsumption of kiwi fruit. The gret mount of dietry fier in kiwi fruit helps in deresing the proility of olon ner. Kiwi's ntioxidnt properties help in proteting the ody ginst free Corresponding Author: Rsh M. Ngi, Deprtment of Home Eonomis, Fulty of Speifi Edution, Mnsour University, Egypt. 1

2 World J. Med. Si., 9 (1): 01-07, 2013 rdils. The flvonoids present in kiwi fruits protet the negtive. The rest of rts were dministered pretmol ells from oxidtive dmge nd in turn, help in gurding to indue liver injury nd lssified into ontrol positive the DNA from muttion nd dmge [5, 6]. Methionine is nd treted groups whih were methionine, kiwi powder n mino id ommonly found in niml-sed protein nd kiwi powder with methionine groups. The experiment nd some fruits nd vegetles nd is onsidered n ontinued for 60 dys. Dily food intke (FI) nd weekly essentil nutrient euse ody doesn't synthesize ody weight gin (BWG) were reorded. Feed effiieny it.methionine ws needed for protein, espeilly musle rtio (FER) nd protein effiieny rtio (PER) were fiers, onnetive tissue nd enzymes tht needs for determined y Chpmn et l. [11]. At the end of helthy metolism nd growth [7]. Methionine is lso experiment, rts were nesthetized nd lood smple were lipotropi ompound tht helps with metolism nd olleted from hepti portl vein in len entrifuge reks down ft. It n lso help with heltion, whih is tues. Liver ws removed nd lotted on filter pper. the removl of hevy metls from the ody to ensure tht the liver, kidneys nd ldder remin helthy. This mino Biohemil Anlysis: The lood ws left to ogulte id preserves rtery funtion nd mintins helthy nils, then entrifuged t 3000 rpm for 15 minutes to otin hir nd skin [8]. serum. Serum sprtte nd lnine minotrnsferse The present study imed to investigte the (AST, ALT) tivity, lkline phosphtse (ALP) nd effet of onsumption of kiwi fruit nd methionine gmm glutmyle trnsferse ( GT) enzymes tivity were on pretmol indued liver toxiity in experimentl estimted ording to Reitmn nd Frnkel [12], Drper rts. nd Hdley [13] nd Kind nd King [14], respetively. Serum totl iliruin, totl protein, lumin nd gloulin MATERIALS AND METHODS were determined ording to Jendrssik [15], Weihselum [16], Brtholomev nd Delny [17] nd Mterils: Coles [18], respetively. Liver holesterol, totl lipids, triglyeride nd glyogen were determined ording to Kiwi fruit ws otined from lol mrket, wshed Rihmond [19], Folh et l. [20], Sheletter nd Nussel with tp wter nd dried t 60 C then rushed to [21] nd Rerup nd Lundquist [22], respetively. Liver fine powder nd dded to sl diet s 10%. superoxide dismutse (SOD), glutthione peroxidse Pretmol drug ws otined from Khir Phrm (GPX), glutthione S-trnsferse (GST), tlse nd &Chem. Ind. Co. Ciro- Egypt. The rt reeived mlondildehyde (MDA) were estimted ording to single dose of 2 g/kg y stomh tue to indue liver Beuhmp nd Fridovih [23], Weiss et l. [24], Ellmn injury [9]. [25], Cohen et l. [26] nd Uhiym nd Mihr [27], Methionine powder ws purhsed from El Gomhori respetively. Compny. Methionine powder ws dded to sl diet s 5 g/kg. Sttistil Anlysis: Dt re expressed s men ± SD. Forty dult mle of white lino rts (Sprgue dwley Sttistil nlysis ws done y using nlysis of strin), weighing 160± 5g, provided from of Ntionl vrine (ANOVA) followed y student s t-test nd P Reserh Center, Dokki, Giz, Egypt. Rts were vlues of 5% nd less were onsidered to e signifint housed s groups in wire ges under the norml ording to Artimge nd Berry [28]. lortory onditions. The sl diet: The rt sl diet ws performed ording to Reeves et l. [10]. RESULTS Kits for iohemil nlysis were purhsed from the Gmm Trde Compny for Phrmeutil nd The results of ody weight gin, food intke, feed Chemils, Dokki, Egypt. effiieny rtio nd protein effiieny rtio of the experimentl rts were presented in Tle 1. Otined dt Methods: showed tht the ontrol positive group hd highly Biologil Design: Food nd wter were provided signifint derese in ody weight gin, FI, FER nd PER d-liitum to experimentl nimls for week s t p<0.001 ompred to rts of ontrol negtive group. dpttion period. The rts were rndomly lssified into Liver injured rts groups whih fed diet ontins five groups (8 rts eh). The first group kept s ontrol methionine or kiwi powder or methionine with kiwi powder 2

3 World J. Med. Si., 9 (1): 01-07, 2013 hd signifint derese in BWG (p<0.001&0.01), FER methionine ould lower totl iliruin ompred to ontrol (p<0.001&0.01) nd PER (p<0.01) ompred to rts of positive group ut the vlues of protein, lumin, ontrol negtive group ut hd signifint inrese in gloulin nd A/G were within norml. Kiwi powder BWG, FI, FER nd PER ompred to rts of ontrol onsumption ould lower totl iliruin nd inrese the positive group. The tretment effet of methionine or kiwi gloulin vlue ompred to ontrol positive group ut powder or methionine with kiwi powder onsumption on vlues of protein, lumin nd A/G were within norml. serum ALT, AST, ALP nd GT ws represented in However, Consumption of methionine with kiwi powder Tle 2. The tivities of serum ALT, AST, ALP nd GT showed non signifint differene in these prmeters enzymes were highly signifint inresed t p<0.001 in s shown in Tle 3. ontrol positive group. Consumption of methionine or Pretmol dministrtion ould inrese the levels kiwi powder ould inrese ALT, AST, ALP nd GT t of liver holesterol nd totl lipids nd derese p<0.01 ompred to rts of ontrol negtive group ut triglyeride nd glyogen t p< However, ould derese in these prmeters ompred to rts of onsumption of methionine or methionine with kiwi ontrol positive group. However, Consumption of powder showed norml vlues of these prmeters. methionine with kiwi powder ould improve liver funtion Consumption of kiwi powder showed signifint in pretmol indued liver injury nd ppered within inrese in glyogen ompred to ontrol positive s norml. illustrted in Tle 4. Pretmol dministrtion showed The tivities of serum totl iliruin nd A/G rtio lower vlues of ntioxidnt enzymes s liver SOD, GPX, were signifintly inresed t p<0.001&0.01, respetively GST nd tlse ut showed higher vlue of MDA t nd signifint derese in totl protein nd gloulin t p<0.001 s shown in ontrol positive ompred to p<0.01&0.001, respetively in ontrol positive group ontrol negtive group. Consumption of methionine ompred with ontrol negtive group. Consumption of or methionine with kiwi powder showed signifint Tle 1: Men vlues ± SD of BWG (g), FI (g), FER nd PER of the experimentl rt groups Vriles Control negtive Control positive Methionine Kiwi powder Methionine +Kiwi powder BWG 95.71± ±5.14 *** 61.43±6.13 ** 66.65± ±8.22 FI (g) 16.85±1.84 *** 11.73± ± ± ±1.71 FER 0.094± ±0.003 *** 0.068± ± ±0.002 PER 0.473±0.05 *** 0.298± ± ± ±0.01 Signifint with ontrol group * P<0.05 ** P<0.01 *** P< d Men vlues in eh rw hving similr letters were not signifintly different Tle 2: Men vlues ± SD of serum ALT, AST, ALP nd GT ( /ml) of the experimentl rt groups Vriles Control negtive Control positive Methionine Kiwi powder Methionine +Kiwi powder ALT de 61.15±7.25 *** ±15.16 ** 90.77± ±12.41 d 75.88±8.24 AST d 52.37±6.14 *** 99.11± ± ±8.41 d 65.54±7.13 ALP 70.36±8.45 *** ± ± ± ±9.61 GT 7.34±1.21 *** 12.69± ± ± ±1.10 Signifint with ontrol group * P<0.05 ** P<0.01 *** P< d Men vlues in eh rw hving similr letters were not signifintly different. Tle 3: Men vlues ± SD of serum iliruin, protein, lumin, gloulin (g/dl) nd A/G of the experimentl rt groups Vriles Control negtive Control positive Methionine Kiwi powder Methionine + Kiwi powder Biliruin 1.39±0.19 *** 2.59± ± ± ±0.20 Protein 7.84± ± ± ± ±1.60 Alumin 3.74± ± ± ± ±0.66 Gloulin 4.12±1.01 *** 1.95± ± ± ±0.78 A/G 0.90±0.03 ** 1.81± ± ± ±0.02 Signifint with ontrol group * P<0.05 ** P<0.01 *** P< d Men vlues in eh rw hving similr letters were not signifintly different. 3

4 World J. Med. Si., 9 (1): 01-07, 2013 Tle 4: Men vlues ± SD of liver holesterol, totl lipid, triglyeride nd glyogen (mg/g) of the experimentl rt groups Vriles Control negtive Control positive Methionine Kiwi powder Methionine + Kiwi powder Cholesterol 5.30±1.11 *** 9.35± ± ± ±1.36 Totl lipid 57.14±6.11 *** 73.43± ± ± ±7.21 Triglyeride 2.77±0.76 *** 1.52± ± ± ±0.75 Glyogen 4.1±0.77 *** 2.99± ±0.65 * 3.45± ±0.78 Signifint with ontrol group * P<0.05 ** P<0.01 *** P<0.001 d Men vlues in eh rw hving similr letters were not signifintly different. Tle 5: Men vlues ± SD of liver SOD, GPX, GST, tlse nd MDA of the experimentl groups Vriles Control negtive Control positive Methionine Kiwi powder Methionine+Kiwi powder SOD(mmol/l) 71.69±.55 * 32.59± ± ± ±6.11 GPX(mmol/l) 58.30±6.11 *** 28.11± ± ± ±6.22 GST(mmol/l) 1.11± ±0.03 ** 0.85±0.04 ** 0.80±0.04 ** 0.98±0.03 Ctlse( /l) 43.14± ± ±3.41 ** 31.21± ±5.14 MDA(mmol/l) d 9.67±1.50 *** 23.77± ± ±1.51 * 11.32±1.36 Signifint with ontrol group * P<0.05 ** P<0.01 *** P< d Men vlues in eh rw hving similr letters were not signifintly different. derese in GST nd MDA t p<0.01&0.05 ut It hs een well estlished tht elevted levels of onsumption of kiwi powder showed signifint ALT, AST nd ALP re inditive of ellulr lekge nd derese in GST, tlse nd MDA t p<0.01 ompred loss of funtionl integrity of the hepti ell memrnes to ontrol negtive group. Consumption of methionine or implying heptoellulr dmge. Serum totl protein nd kiwi powder or methionine with kiwi powder showed iliruin levels on the other hnd re relted to the signifint inrese in liver SOD, GPX, GST nd tlse funtion of the hepti ells reveling the funtionl nd signifint derese in liver MDA ompred to sttus of the hepti ell [33, 34]. Biliruin is one of the ontrol positive group. most linil lues to the severity of nerosis nd its umultion is mesure of inding, onjugtion nd DISCUSSION exretory pity of heptoyte. In the present study pretmol heptotoxi rts showed signifint The otined nutritionl results were reveled to the inrese in the level of serum totl iliruin when ft tht the ovlent inding of n oxidtion produt of ompred with ontrol rts [35]. Methionine is gret pretmol is N-etyl-p-enzoquinoneimine nd ntioxidnt s the sulfur it supplies intivtes free sulphydryl groups of protein results in ell nerosis nd rdils. It my lso e used to tret depression, rthritis lipid peroxidtion whih uses heptotoxiity [2, 29]. pin s well s hroni liver disese - lthough these Reserhers hve found tht methionine is lso one of the lims re still under investigtion. The most ommon three mino ids needed y the ody to mnufture medil use of this mino id is s preventtive retine monohydrte, ompound essentil for energy tretment for liver dmge used y etminophen prodution nd musle uilding. Low levels of methionine poisoning [8]. Kiwi ontins lrge numer of rginine, n slow norml growth nd development [30]. Kiwi fruit whih n promote the lood irultion nd enhne the is one of the most nutritious fruits. Kiwi fruit is lso rih working effiieny. Kiwi fruit lmost ontins no ft, ut in nutrition. The fruit ontins vitmin C, vitmin E, it ontins plenty of petin nd vitmin E, whih re very vitmin A, et rotene nd potssium. Vitmin C n enefiil for the helth of hert. At the sme time, it n strengthen the immune system, elerte the heling of lso lower the level of holesterol [36]. Kiwi fruit ontins wound nd promote the sorption of iron. Tiny lk gret mounts of helthy dietry fier nd vriety of edile seeds of kiwi fruit produe fruit oil whih is rih in ntioxidnts. As result, it n effetively prevent nd lph-linolei id (n importnt omeg-3 essentil ftty tret liver disese [37]. Kiwi n prevent the inrese of id). The fruit skin is rih in flvonoid ntioxidnts plsm holesterol, LDL, triglyeride levels nd, of [31, 32]. inresing HDL levels in rts fed with high ft diet. 4

5 World J. Med. Si., 9 (1): 01-07, 2013 The derese of serum MDA levels nd the inrese of CONCLUSION tivity of SOD were signifint in rts dopting kiwi ompound orl liquid or exerise trining efore the In onlusion, the results of this study demonstrte hyperlipidemi model ws estlished while the dt were tht, oth kiwi nd methionine exhiit potent tion not mrked in hyperlipidemi rts. Studies hve shown ginst pretmol indued hepti dmge in rts. Suh tht kiwi is enefiil for reduing AMD. This effet of effets n e orrelted diretly with its ility to redue kiwi fruits is ttriuted to the flvonoid ntioxidnts like lipid peroxidtion nd enhne the ntioxidnt defense et rotene, lutein nd xnthin [38]. sttus. Administrtion of pretmol resulted in signifint inrese in serum nd hepti SOD nd glutthione REFERANCES peroxidse (GPx) tivities with signifint derese in lood nd hepti glutthione (GSH) levels [39]. 1. Roderik, N.M., P.A. Peter nd J.S. Peter, The enzymti ntioxidnt defense system is the nture Pthology of liver. Livingstone, Gret Britin, protetor ginst lipid peroxidtion. SOD, tlse nd Churhill, GPx enzymes re importnt svengers of superoxide ion 2. Wendel, A., S. Feurensteins nd K.H. Konz, nd hydrogen peroxide. These enzymes prevent Aute pretmol intoxition of strved mie leds genertion of hydroxyl rdil nd protet the ellulr to lipid peroxidtion in vivo. Biohem. Phrmol., onstituents from oxidtive dmge. The oservtion tht 28: inresing ntioxidnt enzymes fter onsumption of diet 3. Cho, E., J.M. Seddon, B. Rosner, W.C. Willett nd ontining methionine nd kiwi ws identil with tht of S.E. Hnkinson, Prospetive study of intke of Selvm nd Kurien [30], who reported tht feeding fruits, vegetles, vitmins nd rotenoids nd risk methionine, redued the suseptiility for lipid of ge-relted mulopthy. Arh Ophthlmol., peroxidtion y restortion of the level of free rdil 122(6): svengers. Senevirtne et l. [7] reported tht 4. Montefiori, M., T.K. MGhie, G. Cost nd methionine hs signifint effet on the myordil A.R. Ferguson, Pigments in the fruit of ntioxidnt enzyme tivities nd only hnges in red-fleshed kiwifruit (Atinidi hinensis nd glutthione peroxidse enzyme tivity orrelted with the Atinidi deliios). J. Agri. Food Chem., mrna hnges. These ntioxidnt hnges my hve 53: role in the enefiil effets of methionine in pthologil 5. Hlliwell, B., J.M.C. Gutteridge nd C.E. Cross, rther thn physiologil onditions. Methionine enefits Free rdils, ntioxidnts nd humn liver helth nd its nturl detoxifition funtions. disese: Where re we now? J. L. Clin. Med., This sulfur-ontining mino id helps ids the liver in 119: proessing fts, whih prevents ftty liver disese. 6. Collins, B.H., A. Horsk nd P.M. Hotten 2001, Also y inresing glutthione levels, methionine helps Kiwifruit protets ginst oxidtive DNA dmge in the liver to effetively neutrlize toxins. Methionine humn ells nd in vitro. Nutr. Cner, 39(1): nturlly supports ellulr helth with its powerful 7. Senevirtne, C.K., T. Li, N. Khper nd P.K. Singl, ntioxidnt tivities Effets of methionine on endogenous A hemil nlysis identified sori id nd ntioxidnts in the hert. Am. J. Physiol., numerous other potentil ntioxidnts in kiwi fruit. 277(6): These inluded R-toomonoenol, vitmin E nlog, 8. Hirhe, F., A. Shröder, B. Knoth, G.I. Stngl nd toopherol, R-toopherol, ffei id gluosyl K. Eder, Effet of dietry methionine derivtives, Alph-sitosterol, hlorogeni id nd on plsm nd liver holesterol onentrtions flvones nd flvonones. The ntioxidnt pity of in rts nd expression of hepti genes kiwifruit onstituents hs monitor the quenhing, involved in holesterol metolism. Br. J. Nutr., svenging, or retrding of free-rdil genertion [40]. 95(5): Kiwifruit juie ws oserved to e potent inhiitor of 9. Rfel, B., F. Dniel, S. Him, A. Hussein, M. Zipor, lipid oxidtion nd n effetive elimintor of the oxidtive P. Moshe, Z. Lilin, A. Yon, O. Rn nd H. Zmir, stress induing gent hydrogen peroxide (H2O 2). The juie Hypothyroidism protets rt liver from lso possessed superoxide dismutse like tivity nd Aetminophen heptotoxiity. Digestive Diseses ted s opper-reduing gent in vitro [41]. nd Sienes, 44(6):

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