Nephroprotective and Antioxidant Effects of Parsley Plant Parts Against Gentamicin-Induced Nephrotoxicity in Rats

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1 Ademi Journl of Nutrition 4 (3): , 2015 IN IDI Pulitions, 2015 DI: /idosi.jn Nephroprotetive nd Antioxidnt Effets of Prsley Plnt Prts Aginst Gentmiin-Indued Nephrotoxiity in Rts 1,2 1 1 Nil Y. Mhmoud, Zin A. lem nd Amir M. El-Moslemny 1 Nutrition nd Food iene Deprtment, Fulty of Home Eonomis, Al-Azhr University, Egypt 2 Deprtment of Food iene nd Nutrition, Fulty of iene, Tif University, Tif - Al-Hweih - P.. Box 888, ZIP ode 21974, Tif, KA Astrt: The nephroprotetive nd ntioxidnt effets of prsley plnt s wtery extrt of fresh leves (deotion), fresh leves, seeds nd seeds oil ginst gentmiin (GM)-indued nephrotoxiity in in mle lino rts were investigted. Thirty six mle lino rts (prgue Dwley strin) weight 140±10g gm were investigted. Rts were divided into two min groups, the first group ws used s ontrol negtive fed on the rtion only (6 rts). The seond min group (30 rts) ws divided in to five groups one of them leved fed on sl diet only nd others supplemented their diet with fresh prsley leves (), prsley seeds (), prsley seeds oil () nd orl dministrted with prsley leves extrt (E) for 15 dys. After tht ll groups were injeted intrperitonelly (i.p.) with GM. ne of these groups ws left s positive ontrol group, wheres the other four groups were fed on sl diet previous prsley produts for other 8 dys during injetion with GM. At the end of the experiment iologil dt were lulted, lood smples were tken, internl orgns were olleted, weighted. erum ws seprted to iohemil nlysis. The results indited tht BWG ws deresed due to reeiving prsley leves extrt (E) nd prsley seeds oil (). Feed effiieny rtio hd signifint dereses in C+ve nd supplemented diet groups exept seeds group, whih hd signifint inrese. erum kidney tests nd liver funtion tests were redued signifintly in rts groups reeived prsley produts s ompred to positive ontrol group. GM (i.p.) rts group showed signifint derese in triglyeride, VD-C nd HD-C; on the other hnd, ll supplemented prsley diet groups showed grdully signifint inrese in HD- in, nd groups, while triglyeride nd VD-C showed non-signifint dereses exept group hd signifint derese. erum totl holesterol nd D-C showed signifint inrese of C+ve group, ll supplemented prsley diet indued grdully signifint dereses, the est one in totl holesterol ws group nd D-C ws group. All rts injeted with GM (i.p.) showed signifint derese in GH nd inrese in MDA, ut ll supplemented prsley diet showed inrese in GH nd derese in MDA. This study reommended tht the onsumption of prsley plnt prts my e useful for ptients who suffer from renl diseses nd those on GM therpy. Key words: Nephroprotetive Prsley Gentmiin Biohemistry Nephrotoxi rts INTRDUCTIN ttriuted to the oxidtive stress used y genertion of retive oxygen speies [2, 3]. Aminoglyoside ntiiotis Kidney is n importnt orgn within the humn ody. n stimulte formtion of retive oxygen speies (R) They gurd lood volumes, filter the lood to form urine, nd use oxidtive stress [4]. R svengers nd regulte wter, eletrolytes, id/se lne, produe ntioxidnts n e used to llevite GM-indued some hormones nd prtiipte in metolism of others. nephrotoxiity [5, 6]. Aminoglyoside ntiiotis re At rest n estimted 20% of rdi output flows through employed linilly euse of their potent teriidl the kidney where they re filtered nd reonditioned [1]. tivities, less teril resistne, post-ntiioti Nephrotoxiity used y GM) gentmiin (seems to e effets nd low ost. Gentmiin, ommonly used Corresponding Author: Nil Y. Mhmoud, Nutrition nd Food ienes Deprtment, Fulty of Home Eonomis, Al Azhr University, Tnt, Ghri, Egypt. And Deprtment of Food iene nd Nutrition, Fulty of iene, Tif University, Tif - Al-Hweih - P.. Box 888, ZIP ode 21974, Tif, KA. E-mil: nilshhd@yhoo.om. 113

2 Ad. J. Nutr., 4 (3): , 2015 minoglyoside, is ssoited with n indution of tuulr Nefrtry Compny for Chemil nd Drugs, Tnt, Egypt. nerosis, epithelil oedem of proximl tuules, ellulr Corn strh ws otined from lol mrket, Tnt, Egypt. desqumtion, tuulr firosis, glomerulr ongestion, eeds oil ws purhsed from herl shop (Hrz), perivsulr edem nd inflmmtion, whih ultimtely Ciro, Egypt. eves were otined from lol mrket. show the wy to renl dysfuntion. It is mtter of dete whether we hve promising gents to prevent the Gentmiin: Gentmiin (Grmyin injetion) is one of inidene of gentmiin-indued nephrotoxiity [7]. minoglyoside ntiiotis otined from Memphis Phytotherpy is the prevention nd tretment of Compny for Phrmeutil nd Chemil Industries, disese using plnts, plnt prts nd preprtion mde Ciro, Egypt. It is dispensed in the form of mpoules, from them. Plnts were trditionlly used in phytotherpy eh ontining 40 mg/ml of gentmiin sulphte for re lled mediinl plnts or hers [8]. Aording to prenterl dministrtion. The seleted dose of gentmiin some uthors phytotherpy is the only rnh of herl ws lulted for the rt from humn dose [11]. mediine in whih liense overs photohemistry, phototherpy, phytophrmy nd phytophrmology. Methods It is importnt to mention tht prsley ontins more eves Formultion Deotion: ne hundred grm vitmin C thn lemon, ornge or ny other fruit. It hs ofleves ws put in 1liter of old wter, rought to oil, undnt quntities of other vitmins nd minerls suh simmered for minutes (longer if plnts very hrd), s: pro-vitmin A, vitmin B, vitmin E, vitmin K, et- then left to ool, steep overed for minutes nd then rotene, mgnesium, phosphorus, iron, mngnese, pssed through te striner, to e redy for use [12]. sodium, potssium, sulfur nd lium. It ts like n ntioxidnt (elimintes toxins nd mintins the elstiity perimentl Design nd Animl Groups: Adult mle of the lood vessels), it is generl stimulnt, diureti, lino rts, prgue Dwley strin, weighing (140±10g) ntisepti, nti-infetious, ntirhiti nd more. Among were otined from Vine nd Immunity rgniztion, other effets tht it hs: it strightens the ody nd Helwn Frm, Ciro, Egypt. The nimls were kept in wire immune system, hs enefiil effet over the liver, ges. The diet ws introdued to the rts in speil food spleen, digestive nd endorine orgns [9]. Prsley ups to void sttering of food. Also wter ws provided ontins mny helth enefiting essentil voltile oils tht to the rts. Food nd wter were provided d-liitum nd inlude myristiin, limonene, eugenol nd lph-thujene heked dily. Thirty six dult mle lino rts were two tive ingredients in prsley, myristiin nd piol, divided into two min groups: The first min group (6 rts) ontin mild diureti properties. Prsley seeds oil hs fed on sl diet s ontrol negtive group (C-ve). The een inluded in the diet of pregnnt women nd is seond min group (30 rts) fed on sl diet for 15 dys. reported to inrese diuresis nd plsm protein nd After tht ll groups were injeted intrperitonelly with plsm lium onentrtions [9]. Prsley is rih in poly- GM (10 mg/kg every 24 hr. for eight dys to indue phenoli flvonoid nti-oxidnts inluding piin, pigenin, nephrotoxiity, one of the dverse retion tkes ple) risoeriol nd luteolin; nd hs een rted s one of the [13]. This seond min group ws divided into 5 groups plnt soure with highest nti-oxidnt tivities. Along eh group ontined 6 rts s follows: Group 1: positive with luteolin, the vitmin C found in prsley serves s n ontrol, rts hd fed sl diet only (C+ve). Group 2: rts effetive nti-inflmmtory gent within the ody [10]. hd sl diet nd tue feeding of prsley leves extrt Therefore, the ojetives of this study were to ssess (E) 2ml. Group 3: rts hd sl diet supplemented with nephroprotetive nd ntioxidnt effets of prsley plnt 10% fresh prsley leves (). Group 4: rts hd sl diet prts ginst gentmiin (GM)-indued nephrotoxiity in supplemented with 10% prsley seeds (). Group 5: rts in mle lino rts. hd sl diet supplemented with 10% oil prsley (). At the end of experiments, ll rts were fsted overnight MATERIA AND METHD srified nd the lood smples were olleted, prt of lood ws entrifuged to otin the serum. Internl Mterils: Cellulose, vitmins, minerls, holine hloride, orgns were olleted nd were tken photo to kidneys of glyerol nd neutrl sein, the min soure of protein in ll groups. The orgns were removed (hert, kidney, rts diet, were e otined from El-Gomhoriy Compny spleen, liver nd lung), lened in sline solution, dried y for Chemils nd ortory equipment's, Ciro, Egypt. filter pper nd weighted. Thirty six mle lino rts prgue Dwley strin, were otined from Vine nd Immunity rgniztion, Biologil Evlution: During the experimentl (28 dy), Helwn Frm, Ciro, Egypt. Kits were purhsed from the onsumed diet ws reorded everydy (feed intke) 114

3 Ad. J. Nutr., 4 (3): , 2015 nd ody weight ws reorded every week. Biologil supplemented diet with (), whih reoded signifint evlution of the different diets ws rried out y inreses (14.52±0.33 nd 14.27±0.27g respetively) s determintion of ody weight gin % (BWG %) feed ompred to C-ve group. The dt of ody weight effiieny rtio (FER) [14]. gin (BWG%) efore gentmiin injetion illustrted non-signifint inreses of C +ve group ompred to Biohemil Anlysis: erum retinine [15], serum uri C-ve group (2.87±3.38 nd 5.11±3.46 respetively). id [16, 17] nd ure nitrogen [18]. erum sprtte Prsley seeds () nd fresh prsley leves () groups minotrnsferse (AT) nd lnine minotrnsferse hve non-signifint inreses ompred to C +ve nd (AT) [19], Alumin [20], totl protein [21], totl C-ve groups (6.82±3.68 nd 7.03±10.49 respetively). holesterol [22], triglyerides [23], HD-C [24], serum Prsley leves extrt (E) nd prsley seeds oil () groups VD-C nd D-C [25], GH [26] nd MDA [27] were hve signifint derese s ompred to ontrol groups determined. (-3.46±1.75 nd -5.11±3.46 respetively). After GM injetion (ip) signifint dereses (P<0.05) of ody ttistil Anlysis: Dt re presented in tles s weight gin (BWGT%) our in C +ve group s ompred mens±stndrd devition (.D.). Vlues were sttistilly to C-ve group (6.68 ± nd 2.87±3.11 respetively). nlyzed y one-wy nlysis of vrine (ANVA- Also, ll rts reeived supplemented diet reorded Tukey test) y using P 10.1 softwre pkge. The P non-signifint dereses (-5.46±3.66,-6.35±2.58,-2.76±1.69 vlues <0.05 were onsidered signifint [28]. nd -2.63±1.53 respetively) of BWGT% s ompred to ontrol groups. Feed effiienies rtio showed signifint REUT AND DICUIN derese (P<0.05) in C +ve group ompred to C-ve group (-2.09±0.45 nd 0.63±0.64 respetively), rts dministrted Dt present in Tle (1) showed feeding effet of with (E) hve non-signifint inrese s ompred to C prsley leves extrt (E), fresh prsley leves (), prsley +ve group followed y () nd () groups (-2.10±0.97, seeds () nd prsley seeds oil () on feed intke (FI), -1.32±1.05 nd -1.13±0.99 respetively). The est result ody weight gin % (BWG%), ody weight gin fter ws found in rts reeived supplemented diet with () tretment % (BWGT%) nd feed effiieny rtio (FER) group (0.54±0.51) whih nerly vlue to C-ve group. (M± D) in nephrotoxi rts. Results for feed intke (FI) The present results re in greement with tht high reorded signifint inrese of ontrol (+ve) (14.12±0.39 mount of prsley seeds oil onsumption ws not g) s ompred to ontrol (-ve) group. Rts reeived ssoited with higher weight gin or signifintly supplemented diet of prsley seeds () nd prsley higher risk of developing overweight or oesity in the seeds oil () groups showed non-signifint dereses ontext of the Mediterrnen feed pttern [29]. (P<0.05) (13.77±0.68 nd 13.60±0.68 g respetively), s Besides investigtions exploring the immedite nd ompred to positive ontrol group. n the other hnd, long-term effets of n olive oil-enrihed diet ( diet) rts dministrted prsley leves extrt (E) follows nd prsley seeds oil on Glugon-like peptide 1 (GP-1) Tle 1: Effet of prsley produts on iologil evlution in gentmiin-injeted rts Groups FI g/dy BWG% BWGT% FER 12.73± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.99 Tle 2: Effet of prsley produts on reltive orgns weigh in gentmiin-injeted rts Groups Kidneys liver hert spleen lungs 0.85± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.05 Vlues denote rithmeti mens ± D of the men. Mens with different letters (,,, d) in the sme olumn differ signifintly t (p 0.05) using one wy ANVA test, while those with similr letters re non-signifint. 115

4 Ad. J. Nutr., 4 (3): , 2015 relese nd intestinl ontent, plsm insulin Reltive spleen weight vlues showed signifint onentrtion, gluose tolerne nd pnreti insulin ontent in dult rts tht hd een injeted with streptozotoin during the neontl period (TZ rts). ver 50 dys, the ody weight gin ws lower in the rts fed the oils diet ompred to stndrd diet [30]. Reltive rgns Weight: Tle (2) presented the men vlues of different orgns reltive weights. Reltive kidney weight vlue showed signifint inrese in ontrol (+ve) group s ompred to norml rts group (1.69±0.03 nd 0.85±0.1 respetively). Inresed weight of kidney for ontrol (+) group my refer to nephritis nd eletrolytes retention nd nephron trophy due to injetion with gentmiin [31]. These results gree with study mentioned tht GM inhiits oxidtive phosphoryltion nd redues ATP levels in renl tuulr ells. Hene, GM-enhned R formtion in isolted ortil mitohondri nd R-indued ell deth were found to hve role in GM-medited ute renl filure. The inrese in kidney weight resulted from the oedem tht ws used y drug indued ute tuulr nerosis [32]. All supplemented diet groups with prsley produts showed signifint derese when ompred to ontrol (+ve) group. The est result ws found in (), () nd () whih nerly vlue to C-ve group (0.81±0.03, 0.83±0.04 nd 0.89±0.03 respetively). This improvement in kidney weight is due to presene of polyphenols nd flvones, rotenoids nd vitmin C present in prsley plnt nd reveled improvement nd protetion of renl glomeruli ginst dmge vi hnges in oth the levels nd tivities of ntioxidnt enzymes in kidneys [33]. Also, flvonoid frtion prevents nephrotoxiity, improves kidney funtion nd promotes kidney primry epithelil tuulr ell regenertion [34]. Reltive liver weight vlues showed non-signifint derese in ontrol (+ve) group s ompred to norml rts group (3.66±0.37 nd 3.99±0.53 respetively). All supplemented diet groups with prsley produts showed non-signifint derese (), () nd (E) when ompred with C+ve nd C-ve groups(3.32±0.30, 3.41±0.12 nd 3.11±0.52 respetively), while () showed non-signifint inrese (P<0.05) in omprison with ontrol (+ve) group. Reltive hert weight vlues showed signifint inrese in ontrol (+ve) group s ompred to norml rts group (0.49±0.03 nd 0.36±0.01 respetively). upplemented diets with prsley produts showed signifint derese (P<0.05) when ompred with positive ontrol s follow (), (), () nd (E) groups (0.37±0.03, 0.38±0.04, 0.34±0.04, nd 0.30±0.44, letters (,,, d) in the sme olumn differ signifintly t (p 0.05) using respetively). one wy ANVA test, while those with similr letters re non-signifint. 116 derese in ontrol (+ve) group s ompred to norml rts group. upplemented diets with prsley produts showed signifint inrese (P<0.05) (), (E) nd () when ompred with positive ontrol. The est result ws found in () whih nerly vlue to C-ve group (0.39±0.06 nd 0.45±0.44 respetively). Reltive lungs weight vlue showed non-signifint inrese in ontrol (+ve) group s ompred to norml rts group (0.77±0.02 nd 0.76±0.05 respetively). All supplemented diet groups with prsley produts ppered non-signifint derese in (E), (), () nd () when ompred to C+ve group (0.72±0.10, 0.73±0.07, 0.74±0.05 nd 0.75±0.10 respetively). The dt suggests tht using prsley tretments showed etter protetion for ll reltive orgns weight (kidney, liver, hert nd spleen) s perent of ody weight ompred to non-treted group due to the effet of prsley s ntioxidnt her. Biohemil Anlysis Kidney Funtion Tests: Uri id, retinine nd ure. Tle (3) results present the men vlues of uri id showed signifint inrese in ontrol (+ve) ompred to C-ve group (3.33±0.22 nd 2.45±0.13 mg/d respetively). The rts dministrted with (E) showed signifint derese (P<0.05) of uri id (2.46±0.08 mg/d), whih losed with C-ve group s ompred to ontrol (+ve) group. The only result found in rts reeived () hve signifint derese s ompred to ontrol groups. Also in the sme tle whih represents the men vlues of retinine of ontrol (+ve) group showing signifint inrese ompred to (ontrol-ve) group (1.05±0.27 nd 0.33±0.05 mg/d respetively). Rts onsumed ll supplemented diets showed signifint derese (P<0.05) of retinine level s follows E,, nd whih reorded lower vlues (0.39±0.01, 0.39±0.02, 0.38±0.04 nd 0.36±0.05 mg/d respetively). Tle 3: Effet of prsley produts on kidney funtion tests in gentmiinnephrotoxi rts Groups Uri id mg/d Cretinine mg/d Ure mg/d 2.45± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±8.8 Vlues denote rithmeti mens ± D of the men. Mens with different

5 Ad. J. Nutr., 4 (3): , 2015 In the sme Tle; the men vlue of ure of ontrol (+ve) group showed high signifint inrese s ompred to (ontrol -ve) group (115±3.3 nd 27.66±3.5 mg/d respetively). Rts reeived ll supplemented diet showed signifint derese (P<0.05) in ure s follows E,, nd whih reorded the est effet on ure level (55.00±5.4, 31.66±8.8, 30.3±4.8 nd 23.5±6.4 mg/d respetively). These results supported tht intke of prsley leves deotion 10% s given orlly for 2 months redued onsiderly serum retinine levels [35]. Also, the orl dministrtion of the prsley leves deotion extrt (0.1, 0.25 nd 0.5 g/kg ody wt) for 14 dys signifintly deresed (p < 0.05) the serum ure, uri id, retinine. A omprison ws mde etween the tion of prsley leves deotion extrt nd glienlmide (600 mirog/kg), known ntidieti drug. These dt suggests tht prsley her is effetive in redution of lood ure, retinine nd uri id levels in rts with nephrotoxiity indued y gentmiin euse prsley might hs diuretis effet. The diureti effet my e ttriutle to the phrmologil tivities of myristiin (sympthomimeti tion) nd piol (irritnt effet) [36, 34]. iver Enzymes: Tle (4) illustrtes the results of GPT nd AT whih reorded signifint inrese in ontrol (+ve) group (21.67±2.06 U/) s ompred to ontrol (-ve) group (11.67±0.82 U/). But supplemented diets with prsley produts showed signifint dereses (P<0.05), whih showed vlues of (15.51±2.16, 14.63±2.42, 14.50±1.05 nd 13.16±1.16 U/ respetively) s follows for, E, nd when ompred to ontrol (+ve) rts. o tht, ll supplemented diet with prsley produts improved GPT (AT) of liver disorder rts, the est result ws showed in fresh prsley leves () group. Also, ontrol (+ve) group ws rised in GT sprtte minotrnsferse (AT) vlues s ompred to ontrol (-ve) group (19.7±1.032 nd 16.67±1.67U/ respetively). rl dministrtion with (E) nd supplemented diet with () groups showed signifint derese (P<0.05) s ompred to ontrol (+ve) group (17.67±0.89 nd 17.5±2.34 U/ respetively). n the other hnd, () nd () groups showed non-signifint derese in GT ompred to C+ve group (18.16±1.32 nd 18.5±1.52 U/ respetively), the est effet ws found in () group followed y () group. These results for GPT nd GT re in line with prsley leves deotion extrt signifintly deresed sprtte minotrnsferse (AT) nd lnine Tle 4: Effet of prsley produts on liver enzymes in gentmiin-injeted rts GPT U/ GT U/ 11.67± ±1.67 d 21.67± ± ± ± ± ± ± ± ± ±2.34 Vlues denote rithmeti mens ± D of the men. Mens with different letters (,,, d) in the sme olumn differ signifintly t (p 0.05) using one wy ANVA test, while those with similr letters re non-signifint. minotrnsferse (AT) [35]. Also, serum lnine minotrnsferse level ws signifintly redued y tretment of prsley oil [37]. Prsley seed oil hs een reported to stimulte hepti regenertion in rt model [38]. The improvement in liver funtions due to prsley leves tht ontin flvonoids suh s glyosides of pigenin, luteolin (e.g. piin, luteolin-7-piosyl-gluoside, pigenin-7-gluoside, luteolin-7-digluoside nd voltile oils suh s myristiin (up to 85%), piol, 1,3,8-p-menthtriene, 1-methyl-4-isopropenylenzene, methyl disulfide, monoterpenes (e.g. -nd -pinene, -myrene, -oimene, -phellndrene, p-terpinene, -terpineol) nd sesquiterpenes (e.g. -opene, rotol, ryophyllene) whih hve ntioxidnt effet [9]. Protein frtions: Totl Protein, Alumin, Gloulin nd Alumin/Gloulin (A/G) Rtio: Tle (5) represents the men vlues of totl protein whih showed signifint inrese for ontrol (+ve) group s ompred to (7.4±0.32 nd 7.2±0.62 mg/d, respetively), ut rts reeived supplemented prsley diet showed signifint derese (P<0.05) in totl protein s ompred to ontrol (+ve). The est result ws found in () (7.2±0.16 mg/d) whih is lose with C-ve group nd followed y, nd E groups. In the sme tle results presented the men vlue of lumin in ontrol (+ve) group showed non-signifint derese (3.30±0.27mg/d) s ompred to ontrol (-ve) group. upplemented diet with, nd showed signifint derese (P<0.05) in lumin s ompred to ontrol groups (2.98±0.18, 3.01±0.18 nd 3.26±0.29 respetively). Also gloulin of ontrol (+ve) group showed non-signifint derese s ompred to ontrol (-ve) group (3.30±0.27 nd 3.38±0.09 mg/d respetively). The men vlue of gloulin in E group showed non-signifint inrese (P<0.05) in gloulin (3.33±0.28 mg/d). ther groups, nd illustrted 117

6 Ad. J. Nutr., 4 (3): , 2015 Tle 5: Effet of prsley produts on liver funtion in gentmiin-injeted rts Groups Totl protein mg/d Alumin mg/d Gloulin mg/d A/G rtio 7.2± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.12 Vlues denote rithmeti mens ± D of the men. Mens with different letters (,,, d) in the sme olumn differ signifintly t (p 0.05) using one wy ANVA test, while those with similr letters re non-signifint. signifint derese of gloulin s ompred to ontrol (+ve) group, the lowered vlue ws in group (2.98±0.18 mg/d). Clulted results of lumin/gloulin (A/G) showed non-signifint derese in rtio in ontrol (ve+) s ompred to norml rts (0.79±0.09 nd 0.9±0.15 respetively). Rts fed on supplemented diets reorded non-signifint inrese (P<0.05) in E nd groups s ompred to ontrol (ve+). n other hnd, there ws non-signifint derese in nd groups s ompred to C+ve group (0.73±0.08 nd 0.75±0.11 respetively). The est result ws found in fresh prsley leves extrt. These findings re in greement with tht prsley seeds oil inrese totl serum proteins, lumin nd gloulin. In generl, the useful effet of prsley in improving liver funtion, n e ttriuted to its ility s ntioxidnt, to: 1-regulte the triggering of hepti drug-metolizing enzymes y the formtion of glutthione-onjugte. 2-meliorte the ntioxidnt enzymes (tlse, upper/zin superoxide dismutse (Cu/Zn D), glutthione peroxidse (GPx), glutthione redutse (GR) nd Glutthione trnsferse (GT) tivity in liver whih is enefiil for the hepti detoxifition [39]. 3-reduing oxidtive stress (deresed retive oxygen speies nd lipid peroxidtion) nd lowering inflmmtory ytokines (deresed tumor nerosis ftor- nd interleukin 1 ) nd protein expression (ylooxygense-2, induile nitri oxide synthse, ytosoli phospholipse A2 nd spse-3) [40, 41]. erum ipid Profile: The results in Tle (6) reveled tht the men vlue of totl holesterol ws signifintly inresed in C+ve group ompred to C-ve group (120.5±3.08 nd 91.5±4.08 mg/d respetively). All supplemented diets showed signifint derese (P<0.05) when ompred with ontrol (+ve). Rts groups of,, E nd hve non-signifint inrese with C-ve group (100.6±8.3, 99.2±2.7, 98±7.4 nd 96.8±6.5 mg/d respetively). Tle 6: Effet of prsley produts on lipid profile in gentmiin-injeted rts Groups Totl holesterol mg/d Triglyeride mg/d 91.5± ± ± ±7.8 98± ± ± ± ±8.3 36± ± ±7.2 Vlues denote rithmeti mens ± D of the men. Mens with different letters (,,, d) in the sme olumn differ signifintly t (p 0.05) using one wy ANVA test, while those with similr letters re non-signifint. Tle 7: Effet of prsley produts on holesterol profile in gentmiin-injeted rts Groups HD- mg/d D- mg/d VD- mg/d 43.5± ± ± ±1.2 d 85.5± ± ± ± ± ± ± ± ± ± ± ± ± ±1.4 Vlues denote rithmeti mens ± D of the men. Mens with different letters (,,, d) in the sme olumn differ signifintly t (p 0.05) using one wy ANVA test, while those with similr letters re non-signifint. The men vlue of triglyerides ws signifintly deresed in C+ve group (46.6±7.8 nd 65.7±10.2 mg/d, respetively) s ompred to C-ve. Menwhile triglyerides showed non-signifint derese in E, nd groups, vlues were (40.8±6.6, 40.3±7.2 nd 38.18±7.5 mg/d respetively) when ompred to ontrol (+ve). The lower vlue ws in group (36±1.5 mg/d) whih hd signifint derese with C+ve group. erum Cholesterol Profile: Tle (7) showed signifint derese of (HD-C) in C+ve group (25.6±1.2 nd 43.5±2.1 mg/d respetively) s ompred to ontrol (-ve). Menwhile E group showed non-signifint inrese when ompred with C+ve group (27.6±2.6 mg/d). Feeding rts on, nd supplemented diets indued signifint inrese vlues when ompred with C+ve 118

7 Ad. J. Nutr., 4 (3): , 2015 group (31.8±2.2, 32.5±2.3 nd 41.8±1.6 mg/d respetively). The est result ws found in group whih is nerly to C-ve group. The men vlues of (D-C) showed high signifint inrese in C+ve group s ompred to C-ve group (85.5±2.6 nd 34.8±2.9 mg/d respetively). Menwhile supplemented diets showed signifint derese s follows E,, nd (62.2±8.1, 61.9±4.7, 57.2±6.3 nd 49.2±1.8 mg/d respetively) when ompred to ontrol (+ve) group, the est result ws found in group whih hve lower vlue. The men vlue of (VD-C) ws signifintly deresed in C+ve group s ompred to C-ve group (9.3±1.5 nd 13.1±2.4 mg/d respetively). The supplemented groups with E, nd showed non-signifint derese when ompred with C+ve group (8.1±1.3, 8.1±1.4 nd 7.7±1.5 mg/d respetively). But group hd signifint derese s ompred to C+ve group (7.2±0.4 mg/d). Prsley seeds oil rih diet prevents dietes, s it redues gluose levels, D holesterol" d" nd triglyeride level in lood, it is preisely due to its effet on holesterol tht prsley seeds oil lso prevents series of diseses tht re very frequent in dieti ptients suh s theroslerosis nd rdiovsulr diseses. Most of the prevention strtegies of these vsulr disorders re foused on oesity nd rteril pressure ontrol [42]. The ltter is preisely hieved y using ntihypertensive gents relted to the renin ngiotensin ldosterone system, whih shows its essentil role in the development of the therom plques in dietes. Prsley leves deotion extrt signifintly deresed totl holesterol nd triglyerides. In generl, the useful effet of prsley in improving lipid profile my e due to presene of flvonoids (polyphenols), vriety of ntioxidnts (inluding vitmins C nd E nd the rotenoids) nd fiers whih redued serum triglyeride, totl holesterol nd D y: 1-proteting D holesterol from oxidtion, inhiit ylooxygense nd lipoxygense enzymes, the voltile essentil oils of ommonly used ulinry hers, spies nd herl tes inhiit mevlonte synthesis nd therey suppress holesterol synthesis nd tumor growth [35]. 2-Reduing neutrophil NADPH-oxidse tivity nd plsm onentrtions of oxidized D nd inflmmtory iomrkers [43]. 3-inresing the tivity of tlse nd glutthione nd redued lipid peroxidtion (thiorituri id-retive sustne) in nephropthy rts [40]. 4-inhiiting pltelet ggregtion nd ting s nti-inflmmtory nd nti-tumor gents [44]. Tle 8: Effet of prsley produts on ntioxidnts GH nd lipid peroxide MDA in gentmiin-injeted rts Groups GH µl/g. protein MDA nmol/g e 8.07± ± ±0.23 f 538±8.8 d 4.93± ±10 d 5.22± ± ±0.14 d 451± ±0.10 e 477±6.23 Vlues denote rithmeti mens ± D of the men. Mens with different letters (,,, d) in the sme olumn differ signifintly t (p 0.05) using one wy ANVA test, while those with similr letters re non-signifint. Antioxidnt Enzyme s: Tle (8) illustrted the results of ntioxidnt enzyme of (GH) whih ws signifintly deresed in C+ve group s ompred to C-ve group (4.52±0.23 nd 8.07±0.25 µl/g, respetively). The supplemented groups with, E, nd groups showed signifint inrese when ompred to C+ve group (5.22±0.11, 4.93±0.06 nd 4.73±0.14 µl/g, respetively). The lower vlue ws in group (4.10±0.10) whih hd signifint derese with C+ve group (4.52± 0.23 µl/g). In the sme tle the men vlue of lipid peroxidtion MDA ws signifintly inresed in C+ve group s ompred to C-ve group (538±8.8 nd 249±6.2 nmol/g, respetively), while there ws signifint derese in the men vlue of MDA for supplemented groups. These results gree with tht the dieti group given prsley, serum uri id, potssium nd sodium levels nd liver P deresed, ut GH levels inresed [45]. These results gree with tht GM used signifint inreses in kidney ontent of mlondildehyde (MDA) nd, vitmin E meliorted the rise in renl ontent of MDA nd enhned the renl non-protein thiols (NPH) ontent s well s superoxide dismutse D tivity [46]. And lso gree with tht serum nd renl tissue MDA, lood superoxide nion nd hydrogen peroxide in GENTA were inresed vs CT nd vs VIT C nd deresed in GENTA + VIT C vs GENTA (ll P < 0.05). Prsley is rih in poly-phenoli flvonoid nti-oxidnts inluding piin, pigenin, risoeriol nd luteolin; nd hs een rted s one of the plnt soures with highest nti-oxidnt tivities [47]. Along with luteolin, the vitmin C found in prsley serves s n effetive nti-inflmmtory gent within the ody nd inresing the tivity of tlse nd glutthione nd redued lipid peroxidtion (thiorituri id-retive sustne) in nephropthy rts [48]. In onlusion, this protetive study indited tht iologil evlution ws improved due to reeiving prsley leves extrt (E) dministrted nd supplemented 119

8 Ad. J. Nutr., 4 (3): , 2015 rts diet with prsley fresh leves, prsley seeds nd 10. Buhnn, R.., Toxiity of spies ontining prsley seeds oil s ompred to positive ontrol group methylenedioxyenzen derivtives: A review. J. Food GM (i.p.). Biohemil nlysis of serum kidney tests, liver fety, 1: funtion tests, lipid profile, ntioxidnt enzyme GH 11. Pget, G.E. nd I.M. Brnes, Interspeies redued signifintly in rts groups reeived prsley dosge onversion sheme in evlution of results in produts s ompred to positive ontrol group GM (i.p.) different speies. In: Evlution of Drug Ativities: nd inrese in HD-C nd lipid peroxide MDA euse, Phrmometris, Eds., D.R. urene nd prsley produt prts hve nutritive nd restortive A.. Bhrh, Ademi Press, ondon, UK, properties. Therefore, this study reommends tht intke Vol. I., pp: of prsley produt prts my e enefiil for helth 12. Hemmes, Helde, Hers. Edited y people nd ptients suffer from nephrotoxiity. Andrew Toin, Pulished y outh Austrlin hool of Herl Mediine, Ridge hven, REFERENCE outh Austrli. 13. Biu, K.J., A.D. Joy nd K.A. Merey, Blndy, J. nd M. edky, etures notes on Therpeuti effet of ethnoli extrt of st urology. pulitions of the 1 Ar enter for Hygrophil spinos on gentmiin-indued medil literture nd Islmi rgniztion for nephrotoxiity in rts. Indin J. p. Biol., Medil iene. Kuwit. 48(9): Cuzzore,., E. Mzzon,. Dugo, I. errino, 14. Chpmn, D.G., R. Cstill nd J.A. Cmpell, R.D. Pol, D. Britti, A.D. rro,. Pierpoli, Evlution of protein in food. I. A method for the A.P. Cputi, E. Msini nd D. lvemini, A role determintion of protein effiieny rtio. Cn. J. for superoxide in gentmiin-medited nephropthy Biohem. Physiol., 37: in rts. Eur. J. Phrmol., 450: Fulkner, N.R. nd J.W. King, Fundmentl of 3. Tvfi, M., H. Ahmdv nd nd P. Tooli, nd linil hemistry. 2 ed. Tietz editor. unders Inhiitory effet of olive lef extrt on Phildelphi, pp: gentmiin-indued nephrotoxiity in rts. I. J. Kid. 16. Brhm, D. nd P. Trinder, Dis., 6: Quntittive enzymti olorimetri determintion 4. h,.h. nd J. hht, Formtion of retive of uri id in serum.; plsm or urine. Anlyst., oxygen speies following iotivtion of 97: 142. gentmiin. Free Rd. Biol. Med., 26: Fossti, P.,. Preniple nd G. Berti, Mzzon, E., D. Britti, A.D. rro, A. Cputi nd Enzymti olorimetri method for determintion of P.. Cuzzore, Effet of N-etylysteine on uri id in serum. Clin. Chem., 26: gentmiin-medited nephropthy in rts. Eur. J. 18. Ptton, C.J. nd.r. Crouh, Enzymti Phrmol., 424: olorimetri method for determintion of ure in 6. Mldondo, P.D., D. Brrer,.N. Mdinmpos, serum. Anl. Chem., 49: R. Hernndez-Pndo, M.E. Irr Ruio nd 19. Reitmn,. nd. Frnkel, A olorimetri J. Pedrz-Chverri, Aged grli extrt method for the detrermintion of serum glutmi ttenutes gentmiin-indued renl dmge nd oxloeti nd glutmi pyruvi trnsminses. oxidtive stress in rts. ife i., 20: Am. J. Clin. Pth., 28: Pithi Blkumr, Ankur Rohill nd 20. Drupt, F., Colorimetri method for determintion Arunhlm Thngthirupthi, of lumin. Phrm. Biol., 9: Gentmiin-indued nephrotoxiity: Do we hve 21. onnenwirth, A. nd. Jret, Grd Wholes promising therpeuti pproh to lunt it? th Clinil ortory Methods nd Dignosis. 18 ed Phrmologil Reserh, 62(3): Mosy, ondon, pp: Weiss, R.F. nd V. Fintelmnn, Allin, C.C.,.. Poon nd C.. Chn, nd Herl Mediine. 2 ed., Gedry Thieme Verlg, Enzymti determintion of serum totl holesterol. NewYork, pp: 448. Clin. Chem., 20: Bisset, N.G., Herl Drugs 23. Trinder, P. nd. Ann, Enzymti olorimetri nd Phytophrmeutils (M. Wihtl, Ed., test with lipid lering ftor to determine Germn edition). tuttgrt: medphrm. triglyerides. Clin. Biohem., 6:

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10 Ad. J. Nutr., 4 (3): , Moreir, M.A., M.A. Nsimento, T.A. Bozzo, 48. ee, W.C., C.J. Wng, Y.H. Chen, J.D. Hsu, A. Cintr,.M. d ilv, M.A. Dloni,.Y. Cheng, H.C. Chen nd H.J. ee, M.G. Mouro nd E.M. Hig, Clin Nutr. pii: Polyphenol extrts from Hiisus sdriff (13) inneus ttenute nephropthy in experimentl type 1 dietes. J. Agri. Food Chem., 57: