International Journal of PharmTech Research CODEN (USA): IJPRIF, ISSN: , ISSN(Online): Vol.9, No.12, pp , 2016

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1 Interntionl Journl of PhrmTeh Reserh CODEN (USA): IJPRIF, ISSN: , ISSN(Online): Vol.9, No.12, pp , 2016 Irqi Propolis s ntioxint n protetive therpy for kiney filure tretment of ieti rts Ferous A. Jir 1 *; Nwl K. Jr 2 1 Deprtment of hemistry, ollege of meiine, AL-Qisyi University, IRAQ. 2 Deprtment of hemistry, College of siene, AL-Qisyi University, IRAQ. Astrt : Astrt :Seventy five rts were ivie into five groups (n=15),nmely ontrol group, group stimulting ietes fter 3 weeks of the eginning of the experiment, group of nturl renhe ethnoli extrt of lol propolis (EEP) ily for 6 weeks, group renhe (EEP) for 3 weeks then is stimulte ietes for 3 more weeks, n the fifth group is stimulte ietes fter 3 weeks of the eginning of the experiment n then renhe (EEP) for 3 weeks fter stimultion. At the en of the experiment, ollete smples of loo serum were use to evlute the oxitive sttus y ssessment the Superoxie Dismutse(SOD), Ctlse(CAT), Glutthione-s- Trnsferse (GST), Mlonilehye(MDA), Nitri Oxie (NO), s well s the extent of the injury ws ppointe renl filure of ells to mesure the level of uri i(ua) n serum totl protein(stp). Oserve results were shown signifint erese in oy weight, effetiveness of the ntioxint system, n protein level in the serum, signifint inrese in the level of gluose in the loo, n inrese in the onentrtion of mlonilehye, Nitri Oxie, n Uri i in the serum for the ieti group. On the other hn, the EEP hs h signifint effet in reuing the level of gluose, MDA, NO, Uri i n the ourrene of signifint inrese in the effetiveness of the system ntioxint n the onentrtion of totl serum protein(p <0.05), n improve the struture of the tissue of the kiney. It n e onlue tht the extrt hs ntioxint effetiveness n reue the level of sugr in the loo n thus protet the overll impt of its omplitions suh s kiney filure. Keywors: Irqi Propolis, ntioxint, protetive therpy, kiney filure, ieti rts. Introution Dietes is metoli isese hrterize y high level of sugr in the loo s result of severl resons, inluing lk of insulin seretion or in the effet of insulin, or oth. Continuous exposure to high loo sugr s result of this isese for long time use mny serious omplitions inluing mge or ysfuntion or filure of vrious orgns of the oy, espeilly the eye, kiney, nerve, hert n loo vessels. Renl filure is one of the mjor omplitions of ny type of ietes 1, where there re severl mehnisms using the evolution of kiney filure use y ietes, suh s: Inrese the formtion of Avne glytion en prouts (AGEs), inrese the effetiveness of protein kinse (PKC), inrese the effetiveness of Polyol pthwy mehnism, s well s Autoxition, ll these mehnisms stimulting oxitive stress, n thus the iniene of omplitions using renl filure 2,soinrese the proportion of gluose using inrese the oxitive stress insie the vesiles in the kiney where the effet will e iret euse the vesiles re the trget ell in the se of kiney filure, lso the

2 Ferous A. Jir et l /Interntionl Journl of PhrmTeh Reserh, 2016,9(12): oxitive stressis onsier the reson of oxition of DNA n stimulte mrna to inrese in gene expression for NFK-Bgene (Nuler Ftor Kpp-Bet gene), whih stimultes the proution of inflmmtory proteins suh s TGF-B(Tumor growth ftor-b), Lminin, fironetin, (interlukine1,6) IL-6, IL-1) 3. There re mny plnts n nturl prouts hve the ility to influene on the efense system, whether ntioxint or immune system euse they ontin mny tive ompouns, suh s flvonois n phenols n esters n importnt elements suh s Cu, Mg, C, N, Whih owns the effetiveness of iologil n physiologil s well s the positive n hrterize y non-toxiity 4. In this stuy, Irqi propolis ws use of to emonstrte the effetiveness s ntioxint n its ility to protet the kiney from filure. Mterils n Methos : Experimentl nimls : Seventy-five rts type (Sprgue-Dwley), weighting etween 150 ± 10 gm use uring this stuy.allowe rts pttion in the House of niml efore the experiment for week where fe stnr foo n wter uner onitions of temperture 22-25Cᵒ unerwent meil tests efore the eginning of the experiment to mke sure of the sfety of them helths. Ethnoli extrt preprtion : Colletepropolis from ifferent res in the ity of Diwniyh / Irq n ut into smll piees n then grin to power, then sift the power to get thesuitle size, then getting pure rw propolis epening on the wy of 5,n then onuteesriptive tests epening on the wy 6, to mke sure the presene of iologilly tive ompouns n ntioxint. PreprtionStreptozotoin : STZ ws prepre y metho of (Shin et l, 2009) 7. Stimultion ietes : Stimulting ietes y injetion fsting rts for more thn 16 hours with single ose of STZ (ip) onentrtion of 60 mg / kg of the weight of the rt. STZ prepre in uffer solution of itrte (PH 4.5) n prepre immeitely efore injetion.been onfirme y high levels of gluose in the loo fter 72 hours fter injetion using evie (Au-Chek), n the result epens on the fifth y fter the injetion is when the gluose levels in loo ws fixe, where is the Dieti Rts t the rte of 200mg / l. Ethnoli extrt of propolis is use s preventive n urtive ginst ietes. Sort experimentl nimls: All rts were ivie rnomly into five groups, fifteen rts per group were istriute s follows: 1. Control group(g1): intt rts renhe orlly with rinking wter (10 ml / kg..w) one ily for six weeks, inluing stoppe t the en of the thir week for five ys fter single injete of itrte uffer (3ml / kg..w). 2. Dieti rts group(g2): rts were renhe rinking wter ((10ml / kg..w) for three weeks, then injete with single ose of solution of STZ for rts fter fsting for the whole night, n then mke sure to stimulte ietes fter five ys, re-osing with rinking wter (10ml / kg..w) for three weeks s well. 3. Tretment intt rts(g3): renhe with EEP t ose of (200mg /kg..w) for three weeks, then injete of itrte uffer (3ml / kg..w) one, then stoppe for five ys ontinue in renhing EEP for other three weeks. 4. Dieti with pre-trete of EEP(G4): rts were pre-trete with lol EEP (200 mg/kg..w) for three weeks, then inue ietes y injete with solution of STZ (60mg / kg..w) n then fter inution of the isese (fter five ys) ws ontinue renhe orlly with rinking wter for three more weeks.

3 Ferous A. Jir et l /Interntionl Journl of PhrmTeh Reserh, 2016,9(12): Post-trete ieti rts(g5): rts were renhe with rinking wter (10ml / kg..w) for three weeks n then fter five (5) ys of inution of the isese, post trete with EEPt ose of (200 mg / kg..w) ily for other three weeks. Every three ys oy weights hve een registere for ll groups, n loo gluose level of the ieti rts groups (G2, G4, G5) were mesure every three ys. After 49 ys from the eginning of the experiment,ll groupswithhel from foo for 12 hours efore loo smples olletion.all rts were nesthetize y injetion xylzine n Ketmine (10mg n 50 mg / kg, respetively), then ollete loo smples nsrifie nimls, smples from kiney in ll groups hve een quikly n fixe in 10%neutrl uffere formlin to mirosopi exmintion then were seprte serum to hol the following tests: 1. Appointment Serum SOD effetiveness epening on the metho (Misr nfriovih, 1972) Ativity of Serum CAT epening on the metho (Aei, 1974) Ativity of Serum GST epening on the metho of (Hig et l,.1974) onentrtion Serum MDA epening on the wy (Guie n Shh, 1989) Serum NO onentrtion epening on the metho of (Hortelno et l,. 1995) Serum UA epening on the metho (Fossti et l, 1980 ( Con. of STP epening on (Biurets et l,. 1999) 14. As well s the smples were teste mirosopilly where opte setions epening on the preprtion metho (Lee, 1968) 15 n the formultion of mirosopi setions epening on the metho (Woo n Eilis, 1994) 16. Sttistil nlysis : All results totls re sttistilly y the progrm SPSS (2010) Version 17Soft wve, metho of hoie inlue (ANOVA) for omprison etween groups, followe y (LSD) for omprison etween groups, the vlue of (P <0.05), s well s ± (stnr error) (SE) Stnr error. Results n Disussion : 1-Boy weight : At the eginning of the experiment,the weights of rts re onvergent ( gm) until the twenty one y, ut fter stimultion ietes, in the y (21), there is isrepny in the weight gin, the first group (98.42 gm), seon (22.17 gm), thir( gm), forth (45.2 gm) n the fifth Group (75.41 gm) fter nother twenty ys (s shown in Figure 1). Through the results i not prove tht the propolis hs ny effet on weight gin in rts nturl (G1, G3) n this orrespons with the results of the reserhers (El-Nhrwy et l,. 2012) 17, ut ontrsts with the results of reserhers (Denliet l,.2005) 18, whom shown inrese in oy weight when propolisws use in oturnix irs, ut in tretment ieti groups (G4, G5) foun signifint meliortion in the oy weight ompre to untrete ieti group (G2) n this n onsiering tht propolis is ntioxint n free rilssvenging 19, n thus is onsiere s regultor for ny metoli efet ompnies ietes. The level of sugr in the loo : Bloo sugr level in G2(ieti group) ws the highest ompre to ll groups t the en of the experiment (P <0.05), ut there ws no signifint ifferene etween the first group n the thir(g1,g3), the groups (4,5) (protetive n tretment) were signifint ifferenes, inluing trete group (5) signifint erese in the level of loo sugr reltive to the preventive group(p <0.05), s shown in tle (1). The results show tht the osge propolis for the ieti rts either efore or fter the inution of the isese hs helpe in reuing the level of sugr in the loo, espeilly for the tretment group were more effetive thn the group preventive, ut stye there signifint ifferenes(p <0.05) etween groups (G4, G5) with nturl groups (G1, G3), where not up to the norml limit.

4 Ferous A. Jir et l /Interntionl Journl of PhrmTeh Reserh, 2016,9(12): Conforme these results with (Mtsue et l,. 2004) 20 where shown results tht the propolis effetive ountermesures to rising ietes, where tht flvonois n poly phenols whih is one of the key elements of propolis, whih owns the effetiveness of nti-oxint n is onsiere s tlyst for the efense system in the tissues of the pnres 21,22,23. There re lso stuies onute y the reserher (Gry et l,.2000) 24 prove tht tnni i is the tlyst for the seretion of insulin n this omponent hs prove its existene y esriptive sttements of lol propolis. The level of ntioxint enzymes (SOD, CAT, GST(: The stuy showe tht there ws signifint erese in the effetiveness of these enzymes in the ieti group to nerly 50% for SOD, n 22% for CAT n 61% for GST, while the tretment ptient groups,the tivity of SOD rehe to oule the tivity of the ieti group, so CAT is lmost up to inrese in the tretment of ieti groups (G4,G5)nerly forth times in ieti group, n for GST, there ws n inrese of more thn thir of the vlue of the effetiveness of the enzyme in the se of illness,tht shown in tle (2). The eline in SOD my e ue toutomtioxitive of hemogloin, whih les to generte free rils suh s superoxie, whih les to the inhiition of SOD 25, s well s oul hve een the loss of importnt elements suh s zin n opper, whih is foun in few rtio in the se of ietes, so onsequently this les to erese the effetiveness of SOD 26, s for Ctlse, Inresing the proportion of gluose in the loo s well s free ftty is forme in ietes, sine the peroxisome n mitohonri ply key role in the ftty i oxition n euse of Free rils, whih use to eline of Performne of mitohonri n peroxisome sttione CAT in them, les to lk of tivity of CAT 27. So my e the intertion of the protein with gluose, whih in turn les to the formtion of ompouns ontining mino is oul e ssoite with Ative site of enzyme (CAT), whih les to hnges in syntheti n proess, n this in turn inhiits the effetiveness of the enzyme 28, s for the GST, whih is n importnt ftor in the removl of toxins through the inhiition of linke ellulr protein, s well s its ility to reue free ril mge y helping to link for eletrophili site of Glutthione 29, for erese of this enzyme les to erese Glutthionereutse euse they re interrelte in their work for the nlysis of hyrogen peroxie or nyorgni Hyroperoxie. Therefore, the high gluose les to onsumption Glutthione n lk of presene whih les to the lk of tivity of the GST 30, n onsiering tht the kiney is the trget orgn for lrge numer of toxins n free rils therefor GST trying to prevent the rsh ws use y the oxitive stress, so the lk of the effetiveness of these enzymes is onsiere s n initor of serious inrese oxitive stress [31], therefor is note erese the effetiveness of the enzymes in the (G2), ut in groups trete either efore or fter the inution of the isese, we fin tht there is mrke improvement, espeilly in the trete group, n this euse of the tretment y EEP hs improve gretly in the level of these enzymes, propolis ontining mny importnt hemil elements suh s (Phenyl Propnois) in ition to the ntioxint ompouns 32, s well s there re mny reserh showe tht lklois ontriute effetive in reuing the progress of renl filure in streptozotoin-inue ieti rt 33. The level of MDA : This stuy showe signifint inrese in the onentrtion of MDA in Group ieti ut in tretment groups y EEP showe tht there is mrke improvement through lower onentrtion of MDA, tht shown in tle (2),where they n instrut the inrese MDA to the lk of effetiveness of the ntioxint system n therey inrese the MAD in the se of kiney filure where MDA is onsiere n importnt initor in the ignosis of vsulr omplitions 34. These results re onsistent with the results of eh of the reserhers(al-s, iy et l, ;Wei et l, ; Osm et l, ), where their reserhes were on rts with ietes. The level of Nitri Oxie, Uri i: For NO Con., foun tht there ws remrkle inrese in its onentrtion in the infete group s well s for Uri i in the loo, while trete groups reore signifint erese in the onentrtions (P <0.05),tht shown in tle (2).

5 Ferous A. Jir et l /Interntionl Journl of PhrmTeh Reserh, 2016,9(12): Reore numerous reports of inrese NO in ieti niml moels, whih stimultes the retinl omplitions to inrese Retinopthy, s well s stimulte the erly stges of kiney filure ue to inrese permeility n integrtion of renl vesiles 38, 39. As for the inrese in the Uri i turne out reports n reserh tht ell mge is not ue to the Uri i, ut euse of free rils for Superoxie, whih proues t the sme time y the enzyme xnthine oxise (XO) 40 n is onsiere to inrese Uri i importnt signl to the eginning of kiney filure ssoite with ietes 41, n through the results of the stuy show tht the osge of EEP gve effetive results in reuing onentrtions of UA, NO where the reserher (Gri-Monivill et l., 2007) 42, tht the ose of Propolis(30mg / ml) inhiits the proution of NO y 65% y reuing the gene expression of the inuile nitri oxie synthse for NO (inos) where iret impt on the inhiition of the tivity of this enzyme, where the omponents of propolis from (queretin, hrysin, glgin, kempferol )ply s inhiitor n strong reutnt for this enzyme. As for Uri i hs een rnke reserher (Soni et l., 2011) 43 numer of nturl prouts suh s propolis s n inhiiting ftor for xnthin oxise enzyme in experiments on lortory nimls (either mouse or rit), lso reserher (Miguel et l., 2011) 44 show tht propolis ontin reltively high mounts of flvonois tht reue the impt of the level of superoxie n therey ontriute to the inhiition of the xnthine oxise, euse the flvonois re linke to Ative site of enzyme, s well s the oxition of xnthine to uri i will not proue the super oxie when there is flvonoi ompouns, therefor Propolis is nturl enhner for kiney work, there re plenty of reserh tht proves the effet of propolis on the work of the kiney in the se of kiney filure, suh s(osm etl., ; Wei etl., Orsoli etl., (. The level of Serum Totl Protein: As for the onentrtions of serum totl Protein The results of the stuy showe the low level of protein in group G2 (p <o.o5) ompre to the norml group (G1, G3) foun tht while there is mrke improvement, espeilly in the tretment group G5,tht shown in tle (2). Attriute the resons for erese STP in the se of ietes to severl resons, inluing euse of the ompouns (Avne oxitive protein prout), s well s ue to free rils, whih proues ompouns Protein Cronyl Prouts (PCO), whih is onsiere sign or eviene of the rsh protein lso onsiere n initor of efet in the ility to nomintion of vesiles ue to inrese permeility of the protein n thus lk the level in serum n inrese in urine lso possile to instrut the lk of the protein to the inhiition of the proess of oxitive phosphoryltion n thus le to inrese the proess of protein tolism n reuing the level of the mount of protein in the loo (Jerine et l., 2011) 47. There re mny reserhes horizon the results of this reserh, inluing (Yssin et l., , Wnke n Wong., ), s reserher (Giurge et l, (the osge of 20mg / 100 gm..w of stnr propolis extrt (SPE) to the hikens for 15 ys use n inrese in the vlue of totl protein s well s the level of gloulin, this reserh showe thtthe purifie propolisoverlp withserum protein using inreses the effetiveness of eruloplsminelso inreses the tivity of the proess of metolism, espeilly (noli effet) n this in turn les to inrese immune response of the oy. As well s (Ali, 1993) [51] showe tht single ose of propolis use inresing the proportion of totl protein for rits, n propolis n e use s strong tlyst immune to humns or nimls.

6 Ferous A. Jir et l /Interntionl Journl of PhrmTeh Reserh, 2016,9(12): Figure (1): Effet ofeep on oy weight gin (g) fter y 21 when inution of ieti y STZ in mle rts. G1= Control rts. G2=Dieti rts. G3= Tretment with EEP. G4= Dieti with Pre- trete of EEP. G5= Dieti with post- trete of EEP. Different letters represent signifint ifferene etween groups(p<0.05). Tle (1): Effet of EEP on Bloo Gluose level in STZ- inue ieti rts. Dys Control G Dieti rts G Tretment with EEP. G Dieti Pre-trete EEP. G with of Dieti with post- trete of EEP. G G1= Control rts. G2=Dieti rts. G3= Tretment with EEP. G4= Dieti with Pre-trete of EEP. G5= Dieti with post- trete of EEP. Different letters represent signifint ifferene etween groups(p<0.05). Vlues represent men stnr error.

7 Ferous A. Jir et l /Interntionl Journl of PhrmTeh Reserh, 2016,9(12): Tle (2): Effet of EEP on serum iohemil prmeters in mle rts Prmeters SOD Ativity U/L CAT Ativity K/ml GST Ativity U/L MDA Con. μmole/l Nitri oxie μmole/l Uri i on.mg/l Control G Dieti rts G e e Tretment with EEP. G Dieti with Pre-trete of EEP. G Dieti with post- trete of EEP. G Totl protein g/l G1= Control rts. G2=Dieti rts. G3=Tretment with Lol EEP. G4= Dieti with Pre-trete of EEP. G5= Dieti with post- trete of EEP. Different letters represent signifint ifferene etween groups(p<0.05). Similr letters represent insignifint ifferene etween groups. Vlues represent men stnr error Histopthologil Chnges: The results of iohemil ltertions tht ensure nephropthy ue to ietes in rts might e insure y mirosopi exmintion of rts kiney, s well s the improvement in kineys funtion y tretment with EEP.

8 Ferous A. Jir et l /Interntionl Journl of PhrmTeh Reserh, 2016,9(12): Figure (2): kiney of STZ-inue ieti in rts fter 3 weeks showing sever vsulr ongestion ntrophy, with vsulr wll estrution(lk rrow), showing res of re loo ells extrvstion into the interstitium n mist the spes etween the tuules(green rrow),oeem hnges(hyropie genertion) with inflmmtory ells. with perivsulr ells nerosis n mil to moerte hyline egenertion(re rrow). 40X H&E. Figure (3): kiney, rts pretrete with EEP efore injetion of STZ-inue ietes prtilly improvement of the historhiteture of kiney withmil to moerte vsulr ongestion(lk rrow), with smll res of re loo ell extrvstion into the interstitium(re rrow). Bowmn's psules re preserve.40x H&E.

9 Ferous A. Jir et l /Interntionl Journl of PhrmTeh Reserh, 2016,9(12): Figure (4): kiney, rts post-trete with EEP fter injetion of STZ-inue ietes, showe, mil vsulr ongestion(re rrow), n shows mil iltion of tuules n Bowmn's psules well preserve(lk rrow), showe ner norml rhiteture of the renl tissue. 40X H&E. Figure (5): kiney of rt trete with lol EEP, there is no pthologil lesions, norml historhiteture of the renl tissue, shows intt tuules n glomeruli, well preserve(lk rrow) norml struture of owmn psules n un remrkle histopthology hnges(re rrow). 40X H&E.

10 Ferous A. Jir et l /Interntionl Journl of PhrmTeh Reserh, 2016,9(12): Conlusion : Through the stuy shows tht the lol propolishs nti-oxint tivity, where it helpe in the orgniztion of metoli proesses y reuing the Oxitive stress tht result from ietes, where reuing the sie effets use y this isese suh s renl filure mrkely,so the stuy showe tht propolis ws ftor in the repir the kiney n reue the level n impt of high gluose in the loo, oth when use efore the inution of the isese (s preventtive), or fter the inution of the isese (therpeuti), ut most effetive when use s nturl prout in the se of tretment Referenes: 1. Ritz, E.; Zeng, X., n Ryhlik, I. Clinil mnifesttion n nturl history of ieti nephropthy. E pu. 2011; 170: Yn, S.F.; Rm, S.; Amy, R., n Shmit, A.M. Mehnisms of isese:avneglytion enprouts n their reeptor in inflmmtion n ietes omplitions. Nt ClinPrt Enorinol Met., 2008; 4: Mesheli, D.S. Role of free rils in pthogenesis of ietes nephropthy. Annls of Afrin Meiine., 2004; 2(3): Tls, Z.S., n Gulhn, M.F. Effets of vrious propolis onentrtions on iohemil n hemtologil prmeters of rinow trout (Onorhynhus mykiss). Eotoxiology Environmentl Sffet,. 2009; 72: Yghoei, S.M.J.; Ghrni, G.R.; Soleimnin, Z.S., n Stri, R. Antimiroil tivity of Irnin Propolis n its hemil omposition. DARU., 2007; 15(1): Hrorne, J.B. " Phytohemils methos". 3 r e. Chpmn n Hll Lt., Lonon, U.K.1973: Shin,A.; Shreesh,K.O. ndivy,v. Chrteriztion of Streptozotoin Inue Dietes Mellitus in Swiss Alino Mie. Glol Journl of phrmology., 2009; 3(2): Misr, H.P., n Friovih, I. The role of Superoxie nion in the outo oxition of epinephrine n simple ssy for Superoxie Dismutse. J. Biol. Chem., 1972; 247: Aei, H. Ctlse. In: "Methos of enzymti nlysis ". 2 n e. Verlg hemi, weinheim. Germny., 1974: Hig, W.H.; Pst, M. J., n Joy, W.B. Glutthione-S-Trnsferse, the first enzymti step in merpturi i formtion. J. Biol. Chem.,1974; 249: Guie, B., n Shh, S.V. Engln in Vivo H 2 O 2 genertion y rt kiney in glyerol-inue renl filure. Am J Physio., 1989; 257(26): Hwn, M.H.; Almshhey, L.A.; Alslmn, A.S.; Stuy of the effets of orl zin supplementtion on peroxynitrite levels, rginse tivity n NO synthse tivity in seminl plsm of Irqi sthenospermi ptients; Repro. Biol. &Enorinol. 2014, 12: Fossti, P.; Prenipe, L., n Berti, G. Determintion of Uri i. Clinihem., 1980; 1(26): Biurets, C. A.; Ashwoo, E. R.,nBruns, D. E. Tietz textook of linil hemistryn moleulr ignostis, 3 r e, AACC. Philelphi. 1999: Lee, L.G. "Mnul of histologi stining methos for the rme fore institute of pthology". 3 r e., MGrw Hill ook Compny, NY, Toronto, Lonon, Syney.1968: Hwn, M.H., Almshhey, L,A.; Alslmn, A.R.; Seminl xnthine oxise: Approprite fluorometri ssy for the exmintion of spermtozo isorers; BioTehnology: An Inin Journl. 2014, 9, El-Nhrwy, W.A.; Wh, S.M.; n Elurssi, I.S. The effet of propolis ginst Monosoium Glutmte (MSG) Toxi Effets on some Biohemil Aspets of kiney. Life SienJournl., 2012; 9(4): Hwn, M.H., Almshhey, L,A.; Alslmn, A.R.; Seminl sulfhyryl oxise: Approprite fluorometri ssy for the exmintion of spermtozo isorers; BioTehnology: An Inin Journl. 2014, 9, Vlres, B.L; Grf, U., n Spno, M.A. Inhiitory effet of wter extrt of propolis on oxoruiin- inue somti muttion n reomintion in Drosophil melnogster. Foo Chem. Toxiol.,2008; 46: Mtsue, T.; Euhi, S.; Fujise, T.; Aesunre, K.J.; Doi, S.; Ym, H., n Mtsumoto, K. Strong ntihyperglyemieffet of wter solule frtion of Brzilin propolis n its iotive onstituent, 3, 4, 5-tri-o-ffeoxyl-quini i. Biol. Phrm. Bull., 2004; 27(11):

11 Ferous A. Jir et l /Interntionl Journl of PhrmTeh Reserh, 2016,9(12): Moreno, M.; Isl, M.; Smpietro, A., n Vttuone, M. Comprisonof the free ril-svenging tivity of propolis from severl regions of Argentin. J. Ethnophrmol., 2000; 71: Alslmn, A.R., Almshhey, L.A. n Hwn, M.H. (2013) Zin supplementtion ttenutes lipi peroxition n inreses ntiperoxint tivity in seminl plsm of Irqi sthenospermi men. Life Si. J. 10, El-Sye, S.M.; Ao-Slmn, O.M.; Aly, H.A. n Mnsour, A.M. Potentil nti-ieti n hypolipiemi effets of propolis extrt in streptozotoin- inue ieti rts. Pk. J. Phrm Si., 2009; 22(2): Gry, A. M.; Ysser, H. A. n Fltt, P. R. The tritionl plnt tretment, Smuusnigr (eler), Exihiits Insulin- like n Insulin- relesing tion in vitro. J. Nutr., 2000; 130(1): Aulsmie H. Alt'ee; Mhmou H. Hwn; Lmi A. Almshhey. The lne etween superoxie ismutse n tlse tivities in ser of oese Irqi men, EuroMeiterrnen Biomeil Journl, 2015; 10 (17): Lin, J. The ssoition etween opper ions n per oxitive retion in ieti trt.,nippon Gnk Gkki Zsshi., 1996;100(9). 27. Inh, H.; Jiyoun, L.; Joo, Y.H.; Jehyun, P.; Hi Bhl, L.; Ye-Shih H. n Hunjoo,H.Ctlse efiieny Aelertes Dieti Renl Injury ThroughPeroxisoml Dysfuntion. Originl Artile Dietes.,2012; 1(61): Hwn MH, Ae HN. Dt supporting the spetrophotometri metho for the estimtion of tlse tivity.dt in rief Mr 31;6: Kumri, L., n Mzumer, P.M. Effiy of Murry Konigii Lef Extrt for ttenuting the progression of Dieti Nephropthy in niml moels. Reserh Artile Phrmology.Int J Phrm Bio Si., 2013 ; 4(3): Shjeel, P.S.; Klpnevi, V., n Mohn, V.R. Potentil Anti-ieti, Hypolipiemi n Antioxint Effets of XnthosomSgittifoliumExtrt inalloxn Inue Dieti rts. Int J Phrm PhrmSi., 2013; 1(5): Akgul, S.U. ; Oguz, F.S.; Çlis kn, Y.C.; Kekik, Y.; Gürkn, Y.H.; Türkmen, A.; Nne, I.; n Ayin, I. The Effet of Glutthione S-Trnsferse Polymorphisms n Anti-GSST1 Antioies on Allogrft Funtions in Reipients of Renl Trnsplnt. Trnsplnttion Proeeings, 2012;44, Korkin, L.G. Phenylpropnois s nturlly ourring ntioxints: from plnt efense to humn helth. Cell. Mol. Boil., 2007; 53(1): Kumri, L., n Mzumer, P.M. Effiy of MurryKonigii Lef Extrt for ttenuting the progression of Dieti Nephropthy in niml moels. Reserh Artile Phrmology.Int J Phrm Bio Si., 2013 ; 4(3): Mos, A. A. n A-Allh, Y. Evlution of some iohemil hnges in ieti ptients. Inter CliniChimiAt., 2004; 346: Al-S, iy, J. A.; Alrohn, M. N., n Ismel, A.K. Antioxint tivity of n-utnol extrt of elery (Apiumgrveolens) see in streptozotoin- inue ieti rts. Res. Phrm. Bioteh., 2012; 4(2): Wei, Z.; Minli, C.; Qiyng, S.; Yinghu, L. n Fuling, H. Biologil Ativities of Chines Propolis n Brzilin Propolis on Streptozotoin- Inue Type 1 Dietes Mellitus in Rts. Originl Arttile,e CAM,. 2010; 5: Osm, M.A; Rwhi, H. El-Eel; Cml-Elin, I.H.; El- Hlwny, N., n Mrouk, M.G. Experimentl ieti nephropthy n e prevente y propolis, effet on metoli isturnes n renl oxitive prmeters. Pk.J.Phrm. Si., 2009; 2(22): Prhkr, S.S. Role of Nitri Oxie in Dieti Nephropthy. Seminrs in Nephrology,.2004; 24(4) : To, N., n Nknishi-To, M. Nitri oxie: oulr loo flow, gluom, n ieti retinopthy. ProgRetin Eye Res., 2007; 26: Wu, L.L., n Jmes, T.W. Serum Uri Ai is A Mrker of Inflmmtion n A Mrker Preiting The Risk of Developing CVD, Stroke, Renl Filure n Cner.J Biome L Si., 2008; 1~2 (20) : Spn, S.L.; Yogesh, S.; Amit, S.; Ekt, A.A., n Alok, M. Hyperuriemi, High Serum Ure n Hypoproteinemi re the Risk Ftor for Dietes. Asin J. Me. Si.,2009; 1(2):

12 Ferous A. Jir et l /Interntionl Journl of PhrmTeh Reserh, 2016,9(12): Grí-Meivill, V.; Crespo, I.; Collo, P.S; Esteller, A.; Sánhez Cmpos, S.; Tuñón, M.J., n González-Gllego, J. The nti-inflmmtory flvones queretin n kempferol use inhiition of inuile nitri oxiesynthse, ylooxygense-2 n retive C-protein, n ownregultion of the nuler ftor kpp B pthwy in Chng Liver ells. Europen Journl of Phrmology., 2007; 557(2-3): Soni, J.P.; Prmr, D. R., n Sen, D.J. Feuxostt: The New Genertion novel xnthine oxise Inhiitors. Interntionle Phrmeuti Sieni., 2011; 1 (1): Miguel, M.G.; Nunes, S.; Dnlen, S.A.; Cvo, A., n Antunes, M.D. Antioxint Ativity of Propolis from Algrve. Av. Environ. Biol.,2011; 5(2): Wei, Z.;Ying-Hu, L.; n Min-Li, C. Protetive effets of Chinese n Brzilin propolis tretment ginst heptorenl lesion in ieti rts.hum ExpToxiol., 2011; 9(30) : Orsoli, N.; Sirovin, D.; Koni, M.Z.; Lkovi, G n Gregorovi, G. Effet of Crotin propolis on ieti nephropthy n liver toxiity in mie. BMC Complementry n Alterntive Meiine., 2012; 12: Jerine, S.W.; Knhn, G. n Mlini, P. Effet of Sinpi i on iohemil mrkers n histologil stuies in norml n Streptozotoin inue Dietes in Wistr rts. Int J Phrm Phrm Si., 2011; 1(3): Yssin, M., n Mwfy, N. Protetive Potentil of Glimepirie n Nerium olener Extrt on Lipi Profile, Boy Growth Rte, n Renl Funtion in Streptozotoin Inue Dieti Rts. Turk J Biol., 2007; 31: Wnke, L., n Wong, N. Dietes mellitus ereses the tivity of the lumin promoter in vitro. J Biol Chem., 1991; 266: Giurge, R.; Coprenu,.D n Popesu, H. Effet of stnrize propolisin extrt on the ompostion of hiken musle. ClujulMeil.,1984; 57: Ali,T. Effet of propolis s ntimiroil sustne on some hemil hnge in infete rts. M. S. Thesis Fulty of siene-ciro University, Egypt. *****