Original Article. Musa Toyin Yakubu *1, Olalekan Bukunmi Ogunro 1, Oluwayemisi Beatrice Ojewuyi 2

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1 Irnin Journl of Toxiology Volume 9, No 30, Autumn 2015 Originl Artile Attenution of Biohemil, Hemtologil n Histologil Inies of Alloxn Toxiity in Mle Rts y Aqueous Extrt of Fogi grestis(shweinf. Ex Hiern) Stems Mus Toyin Ykuu *1, Ollekn Bukunmi Ogunro 1, Oluwyemisi Betrie Ojewuyi 2 Downloe from ijt.rkmu..ir t 10: on Wenesy Jnury 2n 2019 Reeive: Aepte: ABSTRACT Bkgroun: The effets of queous extrt of Fogi grestis stem t the oses of 18, 36, n 72 mg/kg oy weight on lloxn-inue toxiity ws investigte in Wistr rts. Methos: In totl, 35 rts of oth sexes (132.80±7.22g) were rnomize into five groups (AE): nimls in group A reeive 0.5 ml of istille wter orlly on ily sis for 15 ys while the lloxnize rts in groups B, C, D n E lso reeive orlly 0.5 ml of istille wter n sme volume of the extrt orresponing to 18, 36, n 72 mg/kg oy weight, respetively fter whih levels of some iomoleules were etermine n histologil hnges evlute. Results: Aministrtion of lloxn signifintly (P<0.05) inrese loo ure nitrogen (BUN)/retinine rtio, levels of serum totl n onjugte iliruin, uri i, N+, K+, C2+ n Cl- s well s tivities of lkline phosphtse (ALP), sprtte minotrnsferse (AST), n lnine minotrnsferse (ALT) in the serum wheres tivities of ALP, AST n ALT in the liver n kiney, erythroytes n leuoytes inies, totl protein, gloulin n PO42- levels s well s lumin/gloulin rtio erese (P<0.05) signifintly. Alloxn lso use severe nerosis of the tuulr epithelil ells in the nephrons n egenertion of the heptoytes. Although ll the oses of the plnt extrt signifintly mitigte these hnges, the reversls t 72 mg/kg oy weight of the extrt ompre well (P>0.05) with their respetive non-lloxnize istille wter trete ontrol nimls in 78% of the prmeters investigte. Conlusion: Overll, the queous extrt of F. grestis stem ttenute the lloxn tretment relte iohemil, hemtologil n histologil hnges in the rts with the 72 mg/kg oy weight hieving totl reversl in 18 out of the 23 prmeters investigte. Keywors: Alloxn, Dietes Mellitus, Fogi grestis, Mitigtion, Reversl. IJT 2015; INTRODUCTION Alloxn is hyrophili n unstle hemil ompoun with shpe similr to tht of gluose tht llows its trnsporttion within the ells of nimls. It is wiely use ietogeni gent in experimentl nimls like rts, ogs n rits to inue Type I ietes [1,2]. It is toxi gluose nlogues tht preferentilly umulte in pnreti et ells vi the Gluose Trnsporter 2. The ytotoxi tion of lloxn involves oxition of essentil sulphyryl (-SH) group, inhiition of gluokinse enzymes, genertion of free rils n isturne of intrellulr lium homeostsis [1,2]. The presene of intrellulr thiols, espeilly glutthione, genertes retive oxygen speies (ROS) in yli reox retion with its reution prout, iluri i [3]. Autoxition of iluri i proues superoxie rils, hyrogen peroxie n, in finl iron-tlyse retion step, hyroxyl rils [4]. These free rils re ultimtely responsile for the eth of the et ells, whih hve prtiulrly low ntioxint efene pity, n the ensuing stte of insulin-epenent lloxn ietes. These rils my lso versely ffet the norml funtioning of the system of experimentl nimls. Lenzen [5] reporte tht protetion ginst the ytotoxi tion of lloxn n iluri i n e provie only y omin- 1. Deprtment of Biohemistry, University of Ilorin, P.M.B 1515, Ilorin, Nigeri. 2. Deprtment of Biologil Sienes, College of Nturl Sienes, Al-Hikmh University, Ilorin, Nigeri. * Corresponing Author: E-mil: tomuyk@yhoo.om

2 Downloe from ijt.rkmu..ir t 10: on Wenesy Jnury 2n 2019 Irnin Journl of Toxiology tion of superoxie ismutse n tlse, whih ompletely prevents reox yling etween lloxn n iluri i, n thus the genertion of ROS speies. Stuies hve lso een reporte in open sientifi literture on ltere iohemil prmeters of the liver n kiney funtions, hemtologil prmeters n historhiteturl hnges following the ministrtion of lloxn n or extrts of meiinl plnts [6-8]. This hs therefore neessitte more reserhes on the effets of meiinl plnts on lloxninue toxiity in nimls. Fogi grestis, lolly known in English s lk phroisi n y the Hus trie of Nigeri s Murshikn Dutse, elong to the Ruiee fmily. It is n eret shru tht is 1-3 feet tll, tomentellous stems with yellow leves. This plnt hs een reporte to ontin sponins, lklois, flvonois, n nthrquinones [9]. The phroisi, ntimiroil n ntiieti tivities of the F. grestis stem hve een sientifilly evlute n reporte [9-11]. Although, the queous extrt of F. grestis stem hve een reportely evlute for its ntiieti tivity t 18, 36 n 72 mg/kg oy weight in lloxn-inue ieti using serum loo gluose, ure, retinine, lipis n hexokinse tivity [11], there is erth of informtion on the possiility of protetive or restortive (ttenution/meliortion) tivities of F. grestis stem on lloxn-inue toxiity using iohemil, hemtologil n histologil inies. Therefore, the present stuy ws unertken to provie informtion on the restortive effets of queous extrt of F. grestis stem on lloxn-inue toxiity in rts using iohemil inies of the liver n kiney funtions, hemtologil prmeters, liver n kiney histology. This investigtion is further stuy on tht previously reporte y Ykuu n Ogunro [11]. MATERIALS AND METHODS Plnt Mteril The plnt smple ws ought from the her sellers t Kulene Mrket, Ilorin, Nigeri. It ws uthentite t the Deprtment of Hortiul- Mus Toyin Ykuu et l ture n Lnspe Tehnology, Feerl Shool of Forestry, Jos, Nigeri. A vouher speimen (2:108) ws eposite t the Deprtmentl Herrium. Experimentl Animls Thirty five lino rts of oth sexes (132.80±7.22g) otine from the Animl Breeing Unit of the Deprtment of Biohemistry, University of Ilorin, Ilorin, Nigeri, were llowe to limtize for 14 ys in luminium ges ple in well-ventilte housing onitions (temperture: 22±3ºC; out 12 h lightrk yle; humiity: %). The nimls were mintine uner this onition throughout the experimentl perio. They were lso llowe free ess to rt pellets (Premier Fee Mill Co. Lt., In, Nigeri) n tp wter. Chemils, Assy Kits n Hemtologil Anlyser Alloxn monohyrte use ws prout of Sigm Chemil Compny, St. Louis, Mo, USA. The ssy kits for totl protein, lumin, ure, uri i, retinine, totl n onjugte iliruin, lkline phosphtse (ALP), sprtte minotrnsferse (AST) n lnine minotrnsferse (ALT) were prouts of Rnox Lortories Lt., Co-Antrim, UK, while tht of hlorie ion ws prout of Quimi Clinil Appli Lt, Ampost, Spin. The ssy kits for soium, potssium, lium n phosphte ions were prouts of Agppe Dignostis Lt, Kerl, Ini. The utomte hemtologil nlyzer SYSMEX KX21 ws prout of SYSMEX Corportion, Hrrier, Jpn. Preprtion of the Extrt The queous extrt of F. grestis stem ws prepre s previously esrie y Ykuu n Ogunro [11]. Animl Grouping n Aministrtion of Alloxn n Extrt A totl of 35 rts of oth sexes were ssigne into five groups, A-E, of seven rts eh suh tht nimls in group A reeive 0.5 ml of istille while those in groups B-E were intrperitonelly injete with 1 ml orresponing to 1393 Volume 9, No 30, Autumn 2015;

3 Downloe from ijt.rkmu..ir t 10: on Wenesy Jnury 2n 2019 Attenution of Biohemil, Hemtologil n 150 mg/kg oy weight of lloxn monohyrte in sterile physiologil sline. After 48 hours of lloxn injetion, the lloxn trete nimls in groups B, C, D n E were ministere 0.5 ml of istille wter n sme volume orresponing to 18, 36 n 72 mg/kg oy weight of F. grestis stem extrt respetively. The istille wter n the extrt were ministere orlly, one ily, for 15 ys etween 08:00-09:00 hours. The nimls were llowe free ess to rt pellets (Premier Fee Mill Co. Lt., In, Nigeri) n ontminnt free tp wter. The pprovl to rry out this stuy ws otine from the Ethil Committee on the Use n Cre of nimls of the Deprtment of Biohemistry, University of Ilorin, Nigeri. The nimls were lso hnle oring to the guielines of NRC [12]. Preprtion of Serum n Tissue Superntnts Twenty four hours fter the lst oses of the extrt n istille wter, the nimls were nesthetize using iethyl ether. The unonsious rts were quikly remove from the jr fter whih the nek re ws lere of fur. The jugulr veins were ut n n liquot of the loo ws ollete into tues ontining heprin for hemtologil nlysis while out 5 ml of the loo ollete into plin tues were left to lot for 30 minutes t room temperture n entrifuge t 1282 x g for 5 minutes. The resulting serum ws ollete into smple ottles with the i of Psteur pipette, store frozen n use within 24 hours of preprtion for the iohemil nlyses. The nimls were therefter issete, the liver n kiney were exise n lotte in lotting pper. The kineys were lso epsulte fter whih these orgns were seprtely weighe n homogenize in ie-ol 0.25M surose solution (1:5 w/v). The homogentes were entrifuge t 1789 x g for 10 minutes to otin the superntnt, whih ws then use within 24 hours for the iohemil nlyses. Determintion of Biohemil Prmeters Biohemil prmeters evlute in the present stuy were s esrie for gloulin, lium, soium, potssium n uri i [13], Irnin Journl of Toxiology lnine minotrnsferse n sprtte minotrnsferse [14], lkline phosphtse [15], totl protein [16], totl n onjugte iliruin [17], hlorie ion [18] n phosphte ions [19]. Others inlue ure [20], retinine [21] n lumin [22]. The lumin:gloulin n loo ure:retinine were ompute from their respetive etermintions. Determintion of Hemtologil Prmeters The hemtologil prmeters (re loo ells (RBC), men orpusulr volume (MCV), men orpusulr hemogloin (MCH), men orpusulr hemogloin onentrtion (MCHC), white loo ells (WBC), neutrophils, eosinophils, sophils, monoytes, lymphoytes n pltelets were etermine using utomte hemtologi nlyser. Histopthologil Exmintion Histopthologil exmintion of the liver n kiney ws one using the proeure esrie y Drury n Wllington [23] n Kruse [24]. The photomirogrphs were oserve using Olympus mirosope onnete to system tht use Presto Imge folio softwre n were pture t x400. Sttistil Anlysis Dt from this stuy were expresse s qulittive for the histopthologil stuies n quntittive for the iohemil n hemtologil stuies. The quntittive t were expresse s men ± SEM of seven etermintions n sttistil nlysis ws one using Dunn Multiple Rnge Test t 5% level of onfiene (P<0.05). All the nlyses were performe using SPSS version 20.0 softwre (SPSS In., Chigo, IL, USA). RESULTS Aministrtion of lloxn signifintly (P<0.05) erese the tivities of ALP, AST n ALT in the liver n kiney, levels of totl protein, gloulin, phosphte ions n ompute lumin/gloulin rtio in the serum of the nimls when ompre with the non-lloxnize istille wter trete ontrol nimls (Tle 1). Furthermore, the sme lloxn ministrtion Volume 9, No 30, Autumn 2015

4 Downloe from ijt.rkmu..ir t 10: on Wenesy Jnury 2n 2019 Irnin Journl of Toxiology signifintly (P<0.05) inrese the tivities of ALP, AST n ALT in the serum of the nimls, serum onentrtions of totl n onjugte iliruin, uri i, soium, potssium, hlorie n lium ions s well s the ompute loo ure nitrogen/retinine rtio (Tle 1). The ministrtion of ll the oses of the extrt signifintly (P<0.05) mitigte n in some ses reverse the trens of these lloxn tretment relte hnges in the iohemil prmeters towrs the ontrol vlues (Tle 1). For instne, while ll the oses signifintly mitigte ginst the hnges in the levels of these prmeters y lloxn, the 72 mg/kg oy weight of the extrt ompletely reverse n restore (P>0.05) the tivities of ALP in the liver, kiney n serum, ASP in the liver n kiney, ALT in the liver n kiney, the levels of serum totl protein, uri i, gloulin, soium, potssium, lium n phosphte ions s well s ompute loo ure nitrogen/retinine n lumin/gloulin rtios orresponing to 78% reversl of the liver n kiney funtion inies of the rts investigte in the present stuy (Tle 1). The signifintly (P<0.05) reue levels of re loo ells, men orpusulr volume, men orpusulr hemogloin, men orpusulr hemogloin onentrtion, neutrophils, monoytes, lymphoytes, eosinophils, sophils n pltelets following the ministrtion of lloxn were ose epenently n signifintly (P<0.05) elevte y the extrt (Tle 2). The elevtion proue y the extrt on ll the hemtologil prmeters exept the re loo ells were not signifintly (P>0.05) higher thn those of the non-lloxnize rts trete with istille wter. Furthermore, the ministrtion of the 72 mg/kg oy weight of the extrt proue levels of lymphoytes, white loo ells, men orpusulr hemogloin onentrtion n men orpusulr hemogloin tht ompre fvourly (P>0.05) with those of the nonlloxnize istille wter trete rts (Tle 2). Conventionl rhiteture of the liver n kiney t the ellulr level ws isplye y the non-lloxnize istille wter trete ontrol rts (Figures 1 n 6 respetively). Aministrtion of lloxn proue severe liver rhitetur- Mus Toyin Ykuu et l l istortion with heptoellulr egenertion, periportl nerosis, ongestion of entrl vein with inflmmtory ell infiltrtion (Figure 2) n severe rhiteturl istortion in the kiney (Figure 7). However, tretment of lloxnize nimls with vrious oses of the extrt showe moerte heptoellulr (Figures 3-5) n norml kiney historhiteture (Figures 8-10). DISCUSSION Numerous niml moels hve een evelope for the pst few ees for stuying ietes mellitus on whih the effiy of hemil ompouns inluing plnt extrts n its prouts s nti-ieti gent(s) n e evlute. Severl proeures tht n e use to inue ietes in nimls inlue hemils like lloxn n streptozotoin, surgil n geneti mnipultions [25]. One of the most potent n wiely use ietogeni gent is lloxn. Alloxn, hemil gent tht inues Type 1 ietes in experimentl nimls, is ure erivtive tht uses seletive nerosis of the β-ells of the pnres [26]. Aprt from neroti effet on the pnres, it lso versely ffet other orgns of the experimentl nimls leing to ltertions in the hemtologil prmeters n iohemil prmeters of orgn funtion tht eventully ulminte into hmpering the norml funtion inies of these orgns. The historhiteture of these orgns re lso not spre uring lloxn toxiity in nimls. Therefore, the nee to oument gents/ompouns inluing meiinl plnts tht n meliorte, ttenute or mitigte these lloxn toxiity nnot e overemphsize. The use of plnts for vrious purposes suh s proviing shelter, s foo, soure of inome, n in folklori mngement of iseses tes k to millenni. In ition, plnts re now een explore to mitigte/ttenute n/or reverse hemil ompoun-inue toxiity in nimls. In the present stuy, F. grestis stem tretment relte ttenution of lloxn- inue toxiity ws ssesse in iologil system using inies suh s iohemil, hemtologil n histologil hnges Volume 9, No 30, Autumn 2015;

5 Attenution of Biohemil, Hemtologil n Irnin Journl of Toxiology Tle 1. Selete liver n kiney funtion inies of lloxnize rts trete with queous extrt of Fogi grestis stem. Downloe from ijt.rkmu..ir t 10: on Wenesy Jnury 2n 2019 Prmeters Liver ALP Serum ALP Liver AST Serum AST Liver ALT Serum ALT Totl Protein (g/l) Gloulin (g/l) Totl Biliruin (µmol/l) Conjugte Biliruin (µmol/l) Alumin: Gloulin rtio Alloxn + F. grestis (mg/kg oy weight) Control Distille w18 ter 140.3± ± ±9 23.0± ± ± ± ± ±10 e 3.8± ± ± ±9 92.3± ±9 e 1.1± ± ± ± ± ± ±5 93.6± ±4 e 13.8± ± ± ± ± ±17 5.9± ± ± ± ±5 25.7± ±6 22.0± ±9 4.5± ±7 2.9± ± ±7 23.0± ±0.1 1:14 9.6±0.2 1:12 9.1±0.1 1: ±0.2 1:8 10.2±0.1 1: Kiney ALP 175.3± ± ± ± ±4 Kiney ALT 104.7± ± ± ± ±9 Kiney AST 130.3± ± ± ± ±10 Uri i (mmol/l) 0.3± ± ± ± ± Serum N (mmol/l) 133.7± ± ± ± ±4 + Serum K (mmol/l) 3.2± ± ± ± ±0.01 Serum Cl (mmol/l) 98.5± ± ± ± ±7 2+ Serum C (mmol/l) 2.6± ± ± ± ± Serum PO4 (mmol/l) 1.1± ± ± ± ±0.01 Bloo ure nitrogen (BUN): retinine rtio 1:3 1:5 1:4 1:3 1:3 Dt re men ± SEM of seven etermintions. Test vlues rrying supersripts ifferent from the ontrol for eh prmeter re signifintly ifferent (P<0.05). Tle 2. Hemtologil prmeters of lloxnize rts ministere queous extrt of Fogi grestis stem. Alloxn + Prmeters RBC ( 1012L-1) MCV (fl) MCH (pg) MCHC (g/l) WBC ( 103 µl-1) Neutrophil (%) Monoytes (%) Lymphoytes (%) Eosinophil (%) Bsophil (%) Pltelets ( 103µL) Control 3.0± ±8 17.9± ± ± ± ± ± ± ± ±13 Distille wter 2.3± ±6e 6.9± ± ± ±0.8e 0.4±0.03e 34.9± ± ± ±13e F. grestis (mg/kg oy weight) ± ± ± ±3 55.3±5 59.7±4 11.2± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±12 Dt re men ± SEM of seven etermintions. Test vlues rrying supersripts ifferent from the ontrol for eh prmeter re signifintly ifferent (P<0.05) Volume 9, No 30, Autumn 2015

6 Irnin Journl of Toxiology Mus Toyin Ykuu et l Downloe from ijt.rkmu..ir t 10: on Wenesy Jnury 2n 2019 RBC: Re Bloo Cells; MCV: Men Corpusulr Volume; MCH: Men Corpusulr Hemogloin; MCHC: Men Corpusulr Hemogloin Conentrtion; WBC: White Bloo Cells Figure 6. Cross setion of the kiney of nonlloxnize rt ministere istille wter (x400; H&E). Figure1. Cross setion of the liver of non- lloxnize rt ministere istille wter (x400; H&E). Figure 7.Cross setion of the kineyof lloxnize rt ministere istille wter (x400; H&E). Figure 2. Cross setion of the liver of lloxnize rt ministere istille wter (x400; H&E). Figure 8. Cross setion of the kiney of lloxnize rt ministere 18 mg/kg oy weight of extrt (x400; H&E). Figure 3. Cross setion of the liver of lloxnize rt ministere 18 mg/kg oy weight of extrt (x400; H&E). Figure 9. Cross setion of the kiney of lloxnize rt ministere 36 mg/kg oy weight of extrt (x400; H&E). Figure 4. Cross setion of the liver of lloxnize rt ministere 36 mg/kg oy weight of extrt (x400; H&E). Figure 10.Cross setion of the kiney of lloxnize rt ministere 72 mg/kg oy weight of extrt (x400; H&E). Figure 5. Cross setion of the liver of lloxnize rt ministere 72 mg/kg oy weight of extrt (x400; H&E). Therefore, hnges in iohemil inies of orgn funtion usully inite impirment of the norml funtioning of suh orgns [27]. The 1397 Volume 9, No 30, Autumn 2015;

7 Downloe from ijt.rkmu..ir t 10: on Wenesy Jnury 2n 2019 Attenution of Biohemil, Hemtologil n iohemil inies investigte in the liver, kiney n serum of the nimls in the present stuy re useful mrkers for ssessing the funtionl pity of these orgns. Mesurement of the tivities of vrious enzymes in tissues n oy fluis ply signifint role in the investigtion n ignosis of iseses [28], n to resonle extent, the toxiity of hemil ompouns inluing those in plnt extrts [29]. Enzymes o not usully originte from serum, ut rther re erive from isintegrtion, metolism n turnover of tissues n loo ells. Therefore, lekge of enzymes from tissues n orgns my eome mnifeste in the serum s inrese tivity [28]. In this stuy, mrker enzymes were ssye se on their speifi lotions in ells, sine it hs een shown tht the site of injury to the ell oul e orrelte n etermine y ssying the level of tivities of mrker enzyme in suh ells [29]. Alkline phosphtse is n etoenzyme of the plsm memrne n is use to ssess the integrity or mge to the plsm memrne [30,31]. The reue liver n kiney lkline phosphtse tivity y lloxn ompnie y orresponing inrese in the serum enzyme suggest permeility hnges proly s result of mge y oxitive prouts of lloxn. The loss of the minotrnsferses (ALT n AST) from the liver n kiney with orresponing inreses in the serum of lloxn trete rts is quite unerstnle sine the enzymes re ytosoli in origin n ny mge to plsm memrne will onsequently le to their lekge to the externl milieu, in this se, the serum. The ministrtion of the extrt mitigte ginst these ltertions in the liver n kiney enzymes onferring ttenution of lloxn toxiity on the extrt. Alumin, totl iliruin n gloulin whih onstitute protein ontent of the ell n e use to ssess the funtionl pity of the liver [32]. The reution in the levels of totl protein, gloulin n the ompute lumin/gloulin rtio y lloxn in the present stuy my e ttriute to iminishe syntheti funtion of the liver proly s onsequene of heptoellulr injury, enhne tolism or exessive loss from the oy whih might e more thn the rte of synthesis [33]. The elevte levels of totl n onjugte iliruin my further orroorte the lloxn tretment relte Irnin Journl of Toxiology toxi hnges in the nimls. These lloxn toxiities with respet to the totl protein omponent of the serum of the nimls were reue in strength y ll the oses of the extrt with omplete restortion/reversl y the 72 mg/kg oy weight on totl protein, gloulin n lumin/gloulin rtios. Cretinine, ure, uri i, eletrolytes re importnt metolites/moleules in the serum of nimls tht n e use to ssess the norml funtioning of the nephrons t oth the gloulr n tuulr levels. Aprt from this, ompute loo ure nitrogen/retinine rtio n lso give n ie of the orgn tht is ffete sine ure is proue y the liver n exrete y the kiney. The elevte levels of uri i n ompute loo ure nitrogen/retinine rtio y the lloxn suggest glomerulr ysfuntion y the hemil ompoun, lloxn, wheres similr elevtions in the serum eletrolytes (N+, K+, Cl-, C2+, s well s reue levels of phosphte ion y lloxn inites verse effets on the tuulr resorption of the eletrolytes. The resorption of these iomoleules n eletrolytes were ttenute y ll the oses of the extrt. It is worthy of note tht the highest ose of the extrt (72 mg/kg oy weight) use in the present stuy exhiite omplete reversl of the lloxn tretment relte hnges on the serum levels of N+, K+, Cl-, C2+ n PO42-. Alloxn exhiite systemi toxiity on hemtologil prmeters investigte s eviene y the erese in RBC n ftors relting to it (MCV, MCH n MCHC) n erese in WBC n ftors relting to it (neutrophils, sophils, eosinophils, lymphoytes, monoytes n pltelets). The reutions in the levels of the hemtologil prmeters y lloxn my e ue to imlne or sene of equilirium in or etween the rte of synthesis/proution of the hemtologil prmeters n their tolism/estrution [34], s onsequene of oxitive prouts or retive speies generte y lloxn. The extrt however mitigte/ttenute the toxi effets of lloxn on the loo prmeters n this might le to restortion of the funtionl pity of the loo. Alloxn, ure erivtive uses seletive nerosis of orgns in rts [25] n its reution prout, iluri i estlishes reox yle with the formtion of superoxie rils [35]. The preservtion of struturl toxiity use Volume 9, No 30, Autumn 2015

8 Irnin Journl of Toxiology lloxn ws further exhiite y ll the oses of the extrt on the historhiteture of the liver n kiney of rts. Downloe from ijt.rkmu..ir t 10: on Wenesy Jnury 2n 2019 CONCLUSION Overll, the queous extrt of F. grestis stems ttenute lloxn-inue funtionl n struturl toxiities in rts. Further stuies to isolte the ompoun tht ring out this relief from lloxn-inue toxiity is neessry. ACKNOWLEDGEMENTS The uthors re grteful to the tehnil ssistne provie y Mr. Dele Aiyepeku of the Deprtment of Biohemistry, University of Ilorin, Ilorin, Nigeri. REFERENCES 1. Skuelski T. The mehnism of tion of lloxn n streptozotoin tion in β- ells of the rt pnres. Physiol Res 2001; 50: Dhnesh N, Johrpurkr A, Shh G, Dhote V, Kshirsgr S, Bhekr R, Jin M. Extenin-4 reues glyemi y inresing liver gluokinse tivity: n insulin inepenent effet. J Dietes 2012; 3. Grover JK, Yv S, Vts V. Meiinl plnts of Ini with nti-ieti potentil. J Ethnophrmol 2002;81: Dey L, Xie JT, Wng A, Wu J, Mlekr SA Yun CS. Anti-hyperglyemi effets of ginseng: omprison root n erry. Phytomeiine2003;10: Lenzen S. The mehnisms of lloxn- n streptozotoin-inue ietes. Dietologi 2008; 51: Aesokn AA, Oyewole OI, Turry Br MS. Kiney n liver funtion prmeters in lloxninue ieti rts trete with Aloe rensis juie extrt. Sierr Leone J Biome Res 2009; 1(1): Iwel EEJ, Olure FD. Hypoglyemi effet, iohemil n histologil hnges of Sponis momin Linn. n Prinri polynr Benth. sees ethnoli extrts in lloxn-inue ieti rts. J Phrmol Toxiol 2011; 6(2): Onyije FM, Avwioro OG, Writimi EG. Evlution of nephrotoxi effet of Buhini monnr on the kiney of lloxn-inue ieti rts. J Phrm Clin Si 2012; 4: Ykuu MT, Aknji MA, Oliji AT. Aphroisi potentils of the queous extrt of Fogi grestis (Shweinf.Ex Heirn) stem in mle lino rts. Asin J Anrol 2005;7: Mus Toyin Ykuu et l 10. Ameen OM, Oltunji G, Att RF, Usmn LA. Antimiroil tivity, ytotoxi test n phytohemil sreening of extrts of the stem of Fogi grestis. Nigerin So Exp Biology J 2011; 11(1): Ykuu MT, Ogunro OB. Effets of queous extrt of Fogi grestis stem in lloxn-inue ieti rts. Bnglesh J Phrmol 2014; 9: Ntionl Reserh Counil. Guie for the re n use of lortory nimls (8th e.). Ntionl Aemies Siene Press. 2011; p Tietz NW. Clinil guie to Lortory Tests. 3r eition, W.B. Suners Compny, Philelphi; Reitmn S, Frnkel S. A olourimetri metho for etermintion of serum glutmteoxloette n pyruvte trnsminse. Am J Clin Pthol 1957; 28: Wright PJ, Lethwoo PD, Plummer DT. Enzymes in rt urine. Alkline phosphtse. Enzymologi 1972; 42: Gornll AC, Brwill CJ, Dvi MM. Determintion of serum protein y mens of Biuret retion. J Biol Chem 1949; 177: Doums BT, Kwok-Cheung PP, Perry BW, Jenrzejzk B, MCom RB, Shffer R, Huse LL. Cnite referene metho for etermintion of totl iliruin in serum: evelopment n vlition. Clin Chem 1985; 31(11): Skeggs LT, Hohstrsser, HC. Thioynte (olorimetri) metho of hlorie estimtion. Clin Chem 10: Fiske CH, Surrow Y. The olorimetri etermintion of phosphorus. J Biol Chem 1925; 66: Venimin MP, Vrkirtzi C. Chemil sis of the rmioi-etyl miro-metho for estimtion of ure, itrulline n rmyl erivtives. Clin Chem 1970; 16: Brtels MD, Bohmer PW. Biohemistry t glne p Doums BT, Wtson WA, Biggs HG. Alumin stnrs n mesurement of serum lumin with romoresol green. Clin Chem 1971; 31: Drury RA, Wllington EAC. Crleton s Histologil Tehnique. 4th eition. Oxfor, Oxfor University Press; Kruse WJ. The rt of exmining n interpreting histologi preprtions. A stuent hnook. Prtheton Pulishing Group, UK. p Etuk EU. Animl moels for stuying ietes mellitus. Agri BiolJ North Am 2010; 1: Ankur R, Shhj A. Alloxn inue ietes: mehnisms n effets. Int J Res Phrm Biome Si 2012; 3(2): Volume 9, No 30, Autumn 2015;

9 Downloe from ijt.rkmu..ir t 10: on Wenesy Jnury 2n 2019 Attenution of Biohemil, Hemtologil n 27. Afolyn AJ, Ykuu MT. Eretile ysfuntion mngement options in Nigeri. JSexul Me 2009; 6(4): Mlomo SO. Toxiologil implition of eftrixone ministrtion in rts. Nigerin J Biohem Mole Biol 2000;15(1): Ykuu MT, Bilis LS, Lwl M, Aknji M A Evlution of selete prmeters of rt n kiney funtion following repete ministrtion of yohimine. Biokemistri 2003; 15: Aknji MA, Aegoke OA, Oloyee OB. Effet of hroni onsumption of metisulphte on the integrity of rt ellulr system. Toxiology 1993; 81: Shhjhn M, Sith KE, Mllik J, ShymlDevi CS. Effet of Solnum trilotum ginst ron tetrhlorie inue hepti mge in lino rts. Inin J Me Res 2004; 120: Gnong WF. Review of Meil Physiology. 20th Eition. Lnge Meil Books/MGrw- Irnin Journl of Toxiology Hill Meil Pulishing Division. USA; p Lkmihi H, Bkhtoui FZ, Ghi CA, Ezoueiri A, El-Jhiri Y, El-Mnsouri A, Zrr B, Loutfi K. Toxiity profile of the queous ethnol root extrt of Corrigiol telephiifoli Pourr. (Cryophyllee) in roents. Eviene-Bse Complementry n Alterntive Meiine 2011; volume 2011: Artile ID pges. 34. Ykuu MT, Aeshin AO, Irhim, OOK. Toxiologil evlution of queous lef Extrt of senn lt in pregnnt wistr Rts. Int J Current Res Rev 2012;04: Armoye OA, Osimoje DO, Akinsy MA, Nneji CM, Ffunso MA, Aemowo OG. Chnges in ntioxint sttus n iohemil inies fter ute ministrtion of rtemether, rtemether -lumefntrine n hlofntrine in rts. Bsi Clinil, PhrmolToxiol 2008; 102: Volume 9, No 30, Autumn 2015