Fawzia Y. Shata, Sayed G. Hassan, Walid S. El-Nattat, Hassan M. Desouky, Amira H. Mohamed and Alaa R. Ahmed

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1 Glol Journl of Phrmology 8 (4): , 2014 ISSN IDOSI Pulitions, 2014 DOI: /idosi.gjp Protetive Effets of Vitmin E, Selenium nd Zin Supplementtion on Hemtologil nd Some Biohemil Prmeters in Pregnnt Rts Exposed to Cdmium Fwzi Y. Sht, Syed G. Hssn, Wlid S. El-Nttt, Hssn M. Desouky, Amir H. Mohmed nd Al R. Ahmed 1 Deprtment of Animl Reprodution nd A.I. Ntionl Reserh Center, Giz, Egypt 2 Deprtment of Clinil Pthology, Fulty of Veterinry Mediine, Ciro University, Egypt Astrt: The im of this study ws to investigte the possile protetive role of vitmin E (vit.e), zin (Zn) nd selenium (Se) s ntioxidnts ginst dmium (Cd) toxiity in pregnnt rts refleted vi ssessment of hemtologil nd some iohemil prmeters. Ninety pregnnt rts were involved nd rndomly lloted into eqully distriuted (n=10) nine groups. The first group ws kept s ontrol group. While, the other eight groups were treted with 0. mg CdCl 2/kg.wt for the first four groups (low dose dmium) nd 1.5 mg CdCl 2/kg.wt for the seond four groups (high dmium dose). Three of the low nd of the high doses exposed dmium groups were treted with one of the following ntioxidnts: 10 mg vitmin E / niml, 2 mg zin sulphte (ZnSO 4) / kg.wt. or 1.5 mg sodium selenite (NSeO ), respetively. Blood smples were olleted in heprinized tues nd used for hemtologil studies nd estimtion of dmium level. The plsm ws seprted to liquots for evlution of zin level nd glutthione peroxidse tivity (GSH-Px). Exposure to oth low nd high Cd doses indued signifint derese in RBC s ount, hemogloin onentrtion nd pked ell volume. In ddition to signifint hypozinemi ws reorded. In high dose Cd exposed group glutthione peroxidse tivity ws signifintly deresed. The whole lood of ll dmium exposed mothers rt ws higher in dmium ompred to those of ontrol group. Tretment with vit.e, Se nd Zn inresed signifintly the erythroyti prmeters nd Zn level nd GSH-Px tivity. Moreover, redution of dmium residul level in lood of mothers rt ws evident. It ould e onluded tht tretment with vit. E, Se nd Zn my hve protetive effet speilly t the low dose Cd exposure whih is refleted on improving the lood prmeters when ompred with Cd treted group. Key words: Cdmium Toxiity Hemtology Biohemistry Antioxidnts Selenium Zin Vit.E. Glutthione Peroxidse INTRODUCTION formtion of metllothioneins nd retive oxygen speies (ROS) leding to ltertions in the ntioxidnt system nd Cdmium (Cd) is n importnt industril nd using oxidtive dmge in red ood ells (RBCs) nd in environmentl pollutnt whih is present in soil, wter, ir vrious tissues whih result in loss of memrne nd food. It is widely distriuted nd highly toxi hevy funtions. Cd is known to indue nemi, redue the metl ple of using dmge to vrious orgns with RBCs ount, hemtorit vlue s well s hemogloin n ext ellulr mehnism of toxiity [1]. It hs een onentrtion [-5]. found tht Cd stimultes free rdil prodution, leding Protetion ginst toxiity of Cd n e to oxidtive deteriortion of lipids, proteins nd DNA nd omplished through the ntioxidnt defense inititing vrious pthologil onditions in humns nd system (AOS). Vit. E, Se nd Zn re mong the nimls [2]. importnt non enzymti ntioxidnt defense system After exposure, dmium enters the lood, where it whih my modulte its toxiity y n ntioxidtive inds to the erythroyti memrne nd stimultes the mehnism. Corresponding Author: Wlid S. El -Nttt, Deprtment of Animl Reprodution nd A.I., Ntionl Reserh Center, Giz, Egypt. 665

2 Glol J. Phrmol., 8 (4): , 2014 Therefore the im of the present study is to investigte the possile protetive influene of vitmin E, selenium nd zin tretment on lood piture nd glutthione peroxidse of pregnnt rts intoxited with dmium. MATERIALS AND METHODS Animls: Mture femle rts (Sprgue Dowly) were otined from Ntionl Reserh Center Animl House. Animls were mted using mture mles. Animls showed vginl plugs nd/ or sperm in vginl smer were onsidered pregnnt. A totl numer of 90 pregnnt rts ws used in this experiment. The experiment ws onduted under norml environmentl onditions of nutrition nd wter supply. Hevy Metls: Cdmium hloride (CdCl ) ws used in two 2 onentrtions (0. nd 1.5 mg/kg.wt.), whih represent 1/200 nd 1/40 of LD50 ording to El Gindy [6]. Antioxidnts: 2 mg Zin sulphte (ZnSO 4) / Kg.wt. ws given ording to Clverie et l. [7]. Vitmin E ( - toopherol ette). It ws ville in soft geltinous psules of 100 mg. Eh psule ws dissolved in 10 ml orn oil nd eh niml ws dministered one ml orlly [8]. 1.5 mg Sodium Selinite (N2SeO ) / Kg.wt. ws given ording to Yiin et l. [9]. Experimentl Design: Rts were rndomly lloted into nine groups (1 9). Animls were exposed to either low or high doses of CdCl 2 either lone or in omintion with ntioxidnts ZnSO 4, vit. E or NSeO s shown in Tle (1) whih illustrtes tretments of the different groups. Smpling Blood Smples: Three lood smples were olleted from the retro oritl venous plexus of ll nimls of the different groups. The first smple ws tken during pregnny (7-10 dys), the seond nd third smples were tken fter 15 nd 0 dys of prturition. The olleted lood smples were reeived into heprinized tues nd used for hemtologil studies nd estimtion of dmium level. A prt of heprinized lood ws entrifuged t 000 r.p.m. for 10 minutes nd the ler superntnt plsm ws kept t 20 C till used for estimtion of zin level nd glutthione peroxidse tivity. Tle 1: Different experimentl groups of pregnnt rts Group No. Tretment* 1 10 Kept s ontrol 2 10 Low dose (L.D.) CdCl 2 0. mg / kg.wt. 10 Low dose CdCl 2+ 2mg ZnSO 4 / kg wt 4 10 Low dose CdCl mg vitmin E / niml 5 10 Low dose CdCl mg Sod. selenite / kg wt High dose (H.D.) CdCl mg/ kg. wt High dose CdCl 2 +2mg ZnSO 4 / kg wt High dose CdCl mg vitmin E / niml 9 10 High dose CdCl mg Sod. selenite / kg wt. *Tretments were dissolved in distilled wter exept vitmin E who ws dissolved in orn oil. Tretments were given in drinking wter. Vitmin E ws given per os. CdCl 2 ws given times/ week from oneption dte till prturition. Antioxidnts were given 5 dys efore mting nd ontinued dily till prturition Cliniopthologil Exmintions Hemtologil Studies: Erythroytes ount (RBC s), pked ell volume (PCV), hemogloin onentrtion (H), Totl leuoyti ount (WBC s) nd differentil leuoyti ount were rried out ording to the tehniques desried y Feldmn et l. [10]. Biohemil Anlysis: Zin: Zin ws determined ording to Johnsen nd Elisson [11]. Glutthione Peroxidse Ativity: This enzyme ws ssyed dopting the method desried y Tmur et l. [12]. Estimtion of Cdmium Residue in Whole Blood: Cdmium onentrtions in smples of whole lood of mothers were determined y Grphite Furne Atomi Asorption Spetrophotometry. All smples were treted with nitri id nd hydrohlori id mixture s desried y Renrd nd Tompkins [1]. Sttistil Anlysis: Dt were sttistilly nlyzed using one wy nlysis of vrine (ANOVA) ording to the method of Snedeor nd Cohrn [14] nd Sttistil Pkge for Soil Siene (SPSS) version RESULTS Erythrogrm: Dt of the effet of different ntioxidnts (Se, Vit.E nd Zn) on the hemogrm (RBCs, H nd PCV) of Cd-exposed rts reveled vrile responses of improvement (Tle 2). 666

3 Glol J. Phrmol., 8 (4): , 2014 Tle 2: Effet of different doses of dmium given with nd without ntioxidntson the erythrogrm of femle rts t different intervls of the experiment Prmeters 6 RBC S (x10 /µl) HB (g/dl) PCV (%) After irth After irth After irth After irth After irth After irth Periods Groups During* pregnny (15 dys) (0 dys) During pregnny (15 dys) (0 dys) During pregnny (15 dys) (0 dys) Control 4.71 ± ± ± ± ± ± ± ± ±0.84 L.D. Cd 4.14 ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.2 Cd + Vit.E.8 ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.60 H.D. Cd.86 ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.84 Cd + Vit.E 4.25 ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±1.12 LSD *Smples were tken 7 to 14 dys during pregnny. Vlues represent mens ±stndrd error. Cd =dmium, L.D. =low dose, H.D. =high dose, Zn =zin, Se =selenium. Mens with different supersripts (,, ) within row re signifintly different t p<0.05 Differene etween mens in the sme olumn higher thn LSD indites signifine. Tle : Effet of different doses of dmium given with nd without ntioxidnts on the red ell indies of femle rts t different intervls of the experiment. Prmeters MCV (fl) MCH (pg) MCHC (g %) After irth After irth After irth After irth After irth After irth Periods Groups During* pregnny (15 dys) (0 dys) During pregnny (15 dys) (0 dys) During pregnny (15 dys) (0 dys) Control ± ± ± ± ± ± ± ± ±1.09 L.D. Cd ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.8.1 ± ± ± ±0.8 Cd + Vit.E ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.86 H.D. Cd ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.56 Cd + Vit.E ± ± ± ± ± ± ± ± ± ± ± ±2.2.7 ± ± ± ± ± ±1.0 LSD *Smples were tken 7 to 14 dys during pregnny Vlues represent mens ±stndrd error. Cd =dmium, L.D. =low dose, H.D. =high dose, Zn =zin, Se =selenium. Mens with different supersripts (,, ) within row re signifintly different t p<0.05 Differene etween mens in the sme olumn higher thn LSD indites signifine. Tle 4: Effet of different doses of dmium given with nd without ntioxidnts on the leuogrm of femle rts t different intervls of the experiment Prmeters TLC (x10 /µl) Lymph (x10 /µl) Neutro (x10 /µl) Mono (x10 /µl) Eosino (x10 /µl) During After After During After After During After After During After After During After After pregn- irth irth pregn- irth irth pregn- irth irth pregn- irth irth pregn- irth irth Periods Groups ny* (15 dys) (0 dys) ny (15 dys) (0 dys) ny (15 dys) (0 dys) ny (15 dys) (0 dys) ny (15 dys) (0 dys) Control ±1.86 ±2.49 ±1.44 ±2.01 ±1.28 ±0.98 ±1.0 ±0.7 ±0.7 ±0.65 ±0.4 ±0.19 ±0.09 ±0.19 ±0.1 L.D. Cd ±0.88 ±0.7 ±1.46 ±0.5 ±0.98 ±1.59 ±0.9 ±0.7 ±0.28 ±0.5 ±0.44 ±0.44 ±0.1 ±0.19 ± ±0.59 ±2.60 ±1.29 ±0.66 ±1.48 ±0.66 ±1.11 ±1.08 ±0.45 ±0.20 ±0.0 ±0.27 ±0.11 ±0.17 ±0.21 Cd + Vit. E ±2.26 ±0.88 ±1.4 ±2.29 ±0.72 ±0.7 ±0.18 ±0.79 ±0.17 ±0.0 ±0.65 ±0.6 ±0.5 ±0.4 ± ±0.88 ±0.41 ±1.9 ±1.6 ±0.88 ±1.27 ±0.55 ±0.14 ±0.45 ±0.6 ±0.5 ±0.05 ±0.26 ±0.4 ±0.4 H.D. Cd ±0.1 ±0.18 ±2.84 ±1.11 ±0.87 ±2.5 ±0.97 ±0.27 ±0.27 ±0.75 ±0.9 ±0.9 ±0.14 ±0.11 ± ±1.44 ±2.02 ±1.20 ±1.20 ±1.44 ±1.0 ±0.60 ±0.77 ±1.04 ±0.42 ±0.29 ±0.57 ±0.11 ±021 ±0.1 Cd + Vit. E ±1.40 ±0.88 ±0.58 ±1.41 ±1.1 ±0.45 ±0.51 ±0.8 ±0.5 ±0.66 ±0.47 ±0.09 ±0.16 ±0. ± ±1.20 ±1.15 ±0.52 ±1.21 ±0.79 ±1.7 ±0.08 ±0.64 ±0.1 ±0.2 ±0.54 ±0.09 ±0.15 ±0.21 ±0.14 LSD *Smples were tken 7 to 14 dys during pregnny. Vlues represent mens ± stndrd error. Cd =dmium, L.D. =low dose, H.D. =high dose, Zn =zin, Se =selenium. Mens with different supersripts (,, ) within row re signifintly different t p<0.05 Differene etween mens in the sme olumn higher thn LSD indites signifine. 667

4 Glol J. Phrmol., 8 (4): , 2014 Tle 5: Effet of different doses of dmium given with nd without ntioxidnts on plsm zin onentrtionin femle rts t different intervls of the experiment Prmeters Zin (µ/dl) Periods Groups During pregnny After irth (15 dys) After irth (0 dys) Control ± ± ± 24.4 L.D. Cd ± ± ± ± ± ± 8.49 Cd + Vit. E ± ± ± ± ± ± H.D. Cd ± ± ± ± ± ± Cd + Vit. E ± ± ± ± ± ± 7.26 LSD *Smples were tken 7 to 14 dys during pregnny Vlues represent mens ± stndrd error. Cd =dmium, L.D. =low dose, H.D. =high dose, Zn =zin, Se =selenium. Mens with different supersripts (,, ) within row re signifintly different t p<0.05 Differene etween mens in the sme olumn higher thn LSD indites signifine. Tle 6: Effet of different doses of dmium given with nd without selenium on the glutthione peroxidse level (u/l) 15 dys fter prturition in femle rts s orrelted with ontrol Groups Control L. D. Cd L.D. H. D. Cd H. D. Glutthione tivity ± ± ± ± ±4.74 Vlues represent mens ± stndrd error (M ± S.E.) Cd =dmium, L.D. =low dose, H.D. =high dose, Se =selenium. Mens with different supersripts (, ) re signifintly different t p<0.05. Tle 7: Effet of different doses of dmium given with nd without ntioxidnts on the dmium level (ppm) in whole lood of femle rts t different intervls of the experiments Periods Tretments During pregnny* After irth (15 dys) After irth (0 dys) Control L.D. Cd Cd +Zn.1.7 Cd + Vit E H.D. Cd Cd + Vit. E Cd=dmium, L.D. =low dose, H.D. =high dose, Zn =zin, Se =selenium. *Smples were tken t 7 to 14 dys during pregnny. Vlues represent pooled smples Dt of red lood ells indies in Cd exposed rts reveled different types of pprent nemi (Tle ). Leuogrm: Men vlues of leuogrm of pregnnt rts reeived doses of dmium hloride with or without ntioxidnts re illustrted in Tle (4). Results showed vrile improvement onerning the different tretments with ntioxidnts (Tle 4). Plsm Biohemil Prmeters Zin Conentrtion: As illustrted in Tle (5), results reveled signifint hypozinemi during pregnny nd 15 dys fter irth in the low dose Cd exposed group nd llover the experimentl intervls in the high dose group. Assessment of the ntioxidnts effet in the low dose Cd exposed pregnnt rts showed signifint elevtion of zin during pregnny, 15 nd 0 dys fter irth in zin nd vit. E treted groups. Also, signifint elevtion of zin during pregnny ws oserved with selenium dministrtion. In the high dose Cd groups, signifint elevtions were notied in zin nd selenium treted groups during pregnny nd 15 dys fter irth. Also, signifint inrese ws notied with vit. E during pregnny. 668

5 Glol J. Phrmol., 8 (4): , 2014 Glutthione Peroxidse Ativity: The effet of dmium Ersteniuk [20] found tht selenium ounterts the exposure on glutthione peroxidse tivity reveled effet of dmium poisoning y its protetive effet on signifint derese t 15 dys fter irth in the high dose stiliztion of metoli proesses in erythroytes tht Cd exposed group ompred to ontrol s shown in prevent the development of oxidtion stress nd hypoxi. Tle (6). Results of leuogrm of pregnnt rts showed signifint Assessment of the effet of selenium s n leuopeni due to lymphopeni followed y signifint ntioxidnt reveled signifint inrese in the low nd leuoytosis due to neutrophili in low dose exposed high dose Cd exposed groups. group. In high dose, vie vers ws ourred. The Estimtion of dmium residue in whole lood of inrese of leukoyti ount my e due to inflmmtory pregnnt rts: As shown in Tle (7), ll the Cd-exposed response to dmium [21] nd minly s result of groups were higher in dmium level in whole lood of neutrophili [22, 2]. Moreover, El-Demerdsh et l. [19] pregnnt rts ompred to ontrol group. The results dded tht leuoytosis indites n tivtion of the reveled tht the high dose Cd treted group hd the niml s immune system. highest level in ll groups wheres, low nd high dose Cd Effet of zin nd vitmin E on oth low nd high groups tht reeived selenium showed redution in the dose dmium exposed groups showed signifint dmium level in lood. leuopeni due to lymphopeni nd neutropeni during pregnny. While there ws signifint leuoytosis due DISCUSSION to lymphoytosis in high dose dmium treted with selenium. These results re in greement with the In the present work, results of erythrogrm showed findings. of El Demerdsh et l. [19] in rts. This indited signifint derese in the vlues of RBC s ount, tht the ntioxidnts were positively effetive in reduing hemogloin onentrtion nd pked ell volume in low the hzrdous effets of CdCl 2 on the immune system nd high dose dmium exposed groups. These findings through equilirting the inrese or derese, into re supported y oservtions of Horignhi et l. [15], stle norml rnge of totl leuoyti ount (TLC). In Nemmihe et l. [16], Knter et l. [5] nd Cinr et l. [17]. this respet, the most pprently effetive tretment on In this respet, it ws reported tht dmium intoxition dmium ws vitmin E. indued oxidtive stress nd ltered the ntioxidnt Zin onentrtion showed signifint derese in system, tht my result in oxidtive dmge y inhiition low nd high dose dmium exposed groups. These + + of erythroyte N - K ATP se leding to loss of ell findings gree with Sow nd Steiert [24]. The memrne integrity nd funtions, shortened life spn of dministrtion of Cd ould indue hnges in the erythroyte nd ourrene of nemi [18, 19]. metolism of essentil minerls nd hypozinemi ould Additionlly, severl studies suggested tht Cd ould e ttriuted to degenertive hnges in the liver [25]. my use impirment of iron sorption leding to the On the other hnd, signifint hyperzinemi ws evident derese the hemogloin synthesis nd would in low dose dmium exposed rts treted with zin nd ontriute to nemi []. vit.e. In this respet, zin exhiits ntioxidtive properties Assessment of the effet of different ntioxidnts on during exposure to Cd through its ility to intert with the hemogrm, Vitmin E nd selenium ehved rther essentil elements suh s Cu nd Fe deresing their similr in their effet in low nd high dose Cd exposed rts ontent in tissues nd retrding the oxidtive proesses where signifint improvement in RBC s ount, pked [26]. This tre element prevents retive oxygen speies ell volume nd hemogloin onentrtion were notied. (ROS) prodution nd is involved in ell memrne These findings re in greement with mny previous stiliztion, metllothionin (Mt) synthesis nd studies on different speies reorded y Krmkr et l. superoxide dismutse (Cu/Zn SOD) struture [25]. [18], Ognjnovi et l. [4], El Demerdsh [19], In the present study, glutthione peroxidse tivity Nemmihe et l. [16] nd Knter et l. [5] in rts inditing showed signifint derese in the high dose dmium tht free rdil svengers nd ntioxidnts suh s exposed group. Similr results were otined in lood of vitmins C, A, ß rotene nd E. re useful in proteting rts [27, 28] liver nd kidney [16, 29-1] of rts fter Cd ginst dmium toxiity. They dded tht presene of dministrtion. The deresed tivity of the GSH-Px my ntioxidnt with CdCl 2 llevited hrmful nd toxi effets result from diret depletion of selenium y Cd or from on hemtologil prmeters nd hd protetive role in insuffiient inorportion of sulphur ontining mino nemi indued y Cd. ids into GSH-Px euse of ompetition with the 669

6 Glol J. Phrmol., 8 (4): , 2014 Cd metllothioniens synthesis [2, 17, 1]. Moreover, Cd toxi effet on the erythroyti prmeters ) resulting in inhiits the tivities of mny enzymes y inding to their ourene of nemi.tretment with ntioxidnts vit E. sulfhydryl groups or y inhiiting the protein synthesis selenium nd zin expressed (exerted) protetive role [2] On the other hnd, Jemi et l. [26] found tht Cd ginst the hrmful effet of Cd through improving the hd no effet on GSH-Px tivity. Menwhile, Ognjnovi lood prmeters, zin level glutthion peroxidse et l. [4] nd Knter et l. [5] oserved signifint tivity. Selenium dministrtion ppered more effiient inrese of RBCs GSH-Px in Cd treted rts. It is known ginst Cd exposure. tht Cd indues the formtion of superoxide nion rdil in RBCs nd it is resonle to expet n inresed REFERENCES tivity of SOD [, 28]. Cd indued n inrese in CAT nd GSH-Px tivities whih my e explined y their 1. WHO, Environmentl Helth Criteri 14, influene on hydrogen peroxide s sustrte whih is Cdmium, 1st ed. World Helth Orgniztion, formed in the proess of dismuttion of superoxide nion Genev, Switzerlnd, pp: rdil [2, 2]. 2. Wiserg, M., P. Joseph, B. Hle nd D. Beyersmnn, GSH-Px tivity showed signifint inrese in high 200. Moleulr nd ellulr mehnisms of dose dmium with selenium-exposed rts. Similr dmiumrinogenesis, Toxiology, 192: oservtions were reported y Ognjnovi et l. [1]. Kosti, M.M., C. Ognjnovi, C. Dimitrijevi, who mentioned tht tretment with selenium elimintes R.V. Ziki, A.Stjn, G.L. Rosi nd R.V. Zivkovi, the toxi effets of dmium on the tivity of GSH-Px nd 199. Cdmium indued hnges of ntioxidnt nd prevents lipid peroxidtion nd oxidtive dmge indued metoli sttus in red lood ells of rts: In vivo y Cd. This protetion inludes the pility of Se to effets. Eur. J. Hemtlo. Ang., 51: lter the distriution of Cd in tissues nd to indue 4. Ognjnoviæ, B.I., S.Z. Pvloviæ, S.D. Mletiæ, inding of Cd-Se omplexes to proteins whih re similr R.V. Zikiæ, A.S. Stjn, R.M. Rdojièiæ, Z.S. Sièiæ, to metllothioneins. Also, it hs een reported tht V.M. Petroviæ, 200. Protetive Influene of selenium supplementtion inreses the tivities of Vitmin E on Antioxidnt Defense System in the selenium-dependent ntioxidnt enzymes suh s GSH-Px Blood of Rts Treted with Cdmium. Physiol. Res., nd TrxR tht ould e due to inresed inorportion of 52: selenoysteine whih is essentil for their tivities [0]. 5. Knter, M., B. Aksu, M. Akpolt, Y.T. Trldlisir, Conerning dmium residue, ll the Cd exposed C. Akts nd H. Uysl Vitmin E Protets groups were higher in dmium level in whole lood of ginst Oxidtive Dmge Cused y Cdmium in the mothers ompred to ontrol. These results re in Blood of Rts. Eur. J. Gen Med., 6(): ordne with Oishi et l. [] nd Sht et l. [4]. 6. El-Gindy, R.M.M., Effet of hevy metl It hs een reported tht pregnny ould moilize the pollution on some iohemil onstituents in lood, hepti dmium, whih n e trnsferred to the plent tissues nd orgns in experimentl niml. Ph.D. of through the lood plsm Chn nd Cherin [5]. These Biohemistry nd Chemistry of nutrition. Fulty of findings simulte tht desried y Tndon et l. [6] Veterinry Mediine. Ciro Univ. who found tht the umultion of Cd in lood ws 7. Clverie, C., R. Corell, D. Mrtin nd C. Diz, deresed signifintly upon o-exposure to vitmin E. Protetive effets of zin on dmium toxiity in The ntioxidnt property of vitmin E seems to e rodents. Biol. Tre Elem. Res., 75: responsile for the oserved protetion of Cd 8. Wrren, S., S. Ptel nd C.M. Kpron, The intoxition. Shikh et l. [2] reported tht zin effet of vitmin E exposure on dmium toxiity in ntgonizes ellulr dmium trnsport nd umultion mouse emryo ells in vitro. Toxiol., 142: y ompeting for inding to sulfhydryl lignds. 9. Yiin, S.J., C.L. Chern, J.Y. Sheu nd T.H. Lin, Pretretment with zin n derese dmium Cdmium - indued liver, hert nd spleen lipid onentrtions in dms' lood [4, 7-9]. In ddition, it peroxidtion in rts nd protetion y selenium. Biol. redues dmium in lood through its exretion in the Tre Elem. Res., 78: urine. 10. Feldmn, B.V., J.G. Zinkl nd N.C. Jin, It ould e onluded tht from the present results Shlm, s Veterinry Hemtology 5Th ed. Le nd tht dmium indued dmge in erythroyti ells (hd Fiiger, Phildelphi, U.S.A. 670

7 Glol J. Phrmol., 8 (4): , Johnsen, O. nd R. Elisson, Evlution of 24. Sow, B. nd E. Steiert, Effet of orl dmium ommerilly ville kit for the olorimetri dministrtion to femle rts during pregnny on determintion of zin. Inter. J. Androl., 10: zin, opper nd iron ontent in plent, fetl liver, 12. Tmur, M., N. Oshino nd B. Chne, Some kidney, intestine nd rin. Arh. Toxiol., 4: hrteristis of hydrogen nd lkylhydro-peroxides 25. Tndon, S.K., S. Singh, P.S. Rsd nd N. Mthur, metolizing systems in rdi tissue. J. Biohem., Hepti nd renl metllothionein indution y 92: n orl equimolr dose of zin, dmium or merury in 1. Renrd, N.E. nd T.A. Tompkins, Evlution of mie. Food Chem. Toxiol., 9: methods for totl selenium determintion in yest. 26. Jemi, H., I. Messoudi, A.E. Chouh nd Bio Tre Elem Res., 88: A.E. Kerkeni, Protetive effet of zin 14. Snedeor, G.W. nd W.C. Cohrne, Sttistil supplementtion on lood ntioxidnt defense Method 7th ed., Ames.: Iow Stte Univ. Press. system in rts exposed to dmium. Journl of Tre 15. Horignhi, H., M. Sto, N. Konno nd M. Fukushim, Elements in Mediine nd Biology, 21: Long- term dmium exposure indues nemi 27. Srkr, S., P. Ydv nd D. Bhtng, Cdmium in rts through hypo-indution of erythropoietin in indued lipid peroxidtion nd the ntioxidnt system the kidneys. Arh. Toxiol., 71: in rt erythroytes: The role of ntioxidnts. Biol. 16. Nemmihe, S., D. Chne-Sri nd P. Guirud, Tre Elem. Res., 11: Role of -toopherol in dmium-indued oxidtive 28. Srkr, S., P. Ydv nd D. Bhtnger, Lipid stress in Wistr rt s lood, liver nd rin. Chemio- peroxidtive dmge on dmium exposure nd Biologil Intertions, 170: ltertions in ntioxidnt system in rt erythroytes: 17. Cinr, M., A.A. Yigit nd G. Ersln, Effets of study with reltion to time, Biometls, 11: vitmin C or vitmin E supplementtion on Cdmium 29. Krulut-Buln, O., S. Bolkent, R. Ynrdg nd indued oxidtive stress nd nemi in roilers. B. Bilgin-Sokmen The Role of Vitmin C, Revue Méd. Vét., 161(10): Vitmin E nd Selenium on Cdmium-Indued Renl 18. Krmkr, R., R. Bhtthry nd M. Chtterjee, Toxiity of Rts. Drug nd Chemil Toxiology, Biohemil, hemtologil nd 1: histopthologil study in reltion to time relted 0. El-Shrky, A.S., A.A. Newiry, M.M. Bdreldeen, dmium indued heptotoxiity in mie. Biometls, S.M. Ewed, S.A. Sheweit, Protetive role of 1: selenium ginst renl toxiity indued y dmium 19. El-Demerdsh, F.M., M.I. Yousef, F.S. Kedwny nd in rts. Toxiology, 25: H.H. Bghddi, Cdmium- indued hnges in 1. Ognjnoviæ, B.I., S.D. Mrkoviæ, S.Z. Pvloviæ, lipid peroxidtion, lood hemtology, iohemil R.V. Ikiæ, A.Š. Štjn nd Z.S. Sièiæ, Effet of prmeters nd semen qulity of mle rts: protetive Chroni Cdmium Exposure on Antioxidnt Defense role of vitmin E nd - rotene. Food nd hemil System in Some Tissues of Rts: Protetive Effet of Toxiol., 42: Selenium. Physiol. Res., 57: Ersteniuk, H.K., Effet of selenium on metoli 2. Shikh, Z.A., T.T. Vund K. Zmn, proesses in erythroytes during dmium Oxidtive stress s mehnism of hroni dmium intoxition. Lik Sprv Mr, 2: indued heptotoxiity nd renl toxiity nd 21. Loose, L.D., J.B. Silkworth nd D. Wrrington, protetion y ntioxidnts. J. Toxiol. Appl. Cdmium-indued phgoyte ytotoxiity. Bull. Phrmol., 154: Environ. Contm. Toxiol., 20: Oishi, S., J. Nkgw nd M. And, Effets of 22. Shizuyo, S., Y. Kyoko, S. Hiromi nd S. Minekzu, dmium dministrtion on the endogenous metl Toxiity, fertility, tertogeniity nd dominnt lne in rts. Biol. Tre Elem. Res., 76: lethl tests in rts dministered dmium 4. Sht F.Y., S.G. Hssn, A.H. Mohmed, H.M. suhronilly II. Fertility, tertogeniity nd Desouky, W.S. El-Nttt nd A.R. Ahmed, dominntlethltests. Eotoxiology nd Evlution of the protetive effet of some Environmentl Sfety, 4: ntioxidnts in -pregnnt rts exposed to dmium 2. Mdej, J.A., Prtiiption of neutrophils in the I- hormonl, tertogeni nd pthologi study. Pro. ytotoxi retion ginst lymphti leukemi ells in th 5 Inter. Conf. Vet. Res. Div., NRC, Ciro, Egypt, mie. Pol. Arh Weter., 25: pp:

8 Glol J. Phrmol., 8 (4): , Chn, H. M. nd M.G. Cherin, 199. Moiliztion of 8. Brzosk, M.M. nd K.J. Moniuszk, Intertion hepti dmium in pregnnt rts. J. Toxiol. Appl. etween dmium nd zin in the orgnism. Food Phrmol., 120: Chem. Toxiol., 9: Tndon, S.K., S. Singh nd M. Dhwn, Yousef, A.E. nd S.M. Srour, Zin s Preventive effet of vitmin E in dmium protetive gent ginst dmium-indued intoxition. Biomed. Environ. Si., 56: tertogeniity nd mternl toxiity in lino rts. 7. Whelton, B.D., D.P. Peterson, E.S. Moretti, Egypt. J. Pth., 18: R.W. Muser nd M.H. Bhtthryy, Hepti levels of dmium zin nd opper in multiporous, Nullporous nd ovritomized mie fed either nutriet-suffiient or defiient diet ontining dmium. Tertology, 119:

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