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ENDOCRINE DISRUPTING ACTIONS OF CADMIUM AND EXPERIMENTAL EVALUATION OF PROTECTION BY GREEN TEA EXTRACT
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2014-05) SHIVAKUMAR, PABBATHI; GOPALA REDDY, A(MAJOR); SRINIVASA RAO, G; ANJANEYULU, Y; RAMANA REDDY, Y; UDAYA KUMAR, M
ABSTRACT : An experimental study was conducted to evaluate the neuro-endocrine disrupting actions of cadmium and the effect of cadmium on the progeny that were born to cadmium exposed rats and to evaluate the protective role of green tea on neuro-endocrine disrupting actions of cadmium in Sprague dawley rats. Rats were randomly divided into 4 groups of 30 rats in each (male rats =12, female rats=18).Group 1 served as Sham control Group 2 treated with CdCl2, Group 3 treated with Green tea extract treatment and Group 4 Cd + green tea extract treatment. Blood was collected from all the groups at monthly intervals for analyzing sero-biochemistry (blood glucose, total cholesterol, HDL-cholesterol, triglycerides, total protein and albumin, biomarkers of cardiovascular, hepatic and renal pathology, and hormonal profile (thyroid profile, sex hormones). The key enzymes concerned with metabolism were assayed. Immune status was studied at the end of 3rd month by phytohaemagglutinin assay. Rats were subjected to neuro-behavioural studies at the end (Elevated plus maze and Morris water maze). Epididymal sperm count in males and estrous cycle pattern in females were studied. At the end of 3 months, 12 rats (6 males and 6 females) from each group were sacrificed to collect various organs and endocrine glands and subjected them to biochemical, histological and electron microscopic studies. Cadmium concentration was estimated in all the treated groups in kidney, testes, liver and brain at the end of 3 months. In all the groups, twelve (12) females were mated at the end of three months with male rats belonging to respective groups/treatments and the treatment was continued till 17th day of gestation. 50% of the pregnant rats in the respective groups were sacrificed on day 19 to study skeletal and soft tissue developmental anomalies and the rest were allowed to normal delivery. The pups of F1 generation from all the groups were kept till weaning (post-natal day 21) and were subjected to sero biochemical, neurobehavioural studies andthyroid hormone profile were estimated. There were significant alterations in sero-biochemistry biomarkers of cardiovascular, hepatic and renal pathology and hormonal profile thyroid profile, group 2 as compared to group 1.Treatment group revealed significant improvement in all the parameters as compared to group 2, while the combination treatment group 4 was found better The histological studies in group 2 revealed marked changes in all the organs studied, while groups 4 revealed moderate changes and groups 1 and 3 revealed no pathologically significant changes. The electron microscopy of kidney, testis and thyroid revealed marked alterations in architecture in group 2, while groups 4 revealed better architecture. There were no significant alteration in the TEM samples of the offspring and there were no skeletal abnormalities in the offspring as evidenced by skeletal staining. The results of the study revealed neuro-endocrine disrupting actions of cadmium and protctive role of green tea in cadmium toxicity. Further studies are warranted to know in detail on the endocrine disrupting actions of cadmium and protective role of green tea at various concentrations.
Open Access
INTERACTION STUDIES ON GYMNEMA SYLVESTRE WITH GLIMEPIRIDE AND INSULIN IN EXPERIMENTAL DIABETES MELLITUS IN RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2013-12) Srikanth, M.K; GOPALA REDDY, A(MAJOR); BHARAVI, K; MADHAVA RAO, T; KONDAL REDDY, K; ANAND KUMAR, A
ABSTRACT: An experimental study was conducted to evaluate the interaction of Gymnema sylvestre extract with insulin and glimepiride in diabetic Sprague dawley rats. Rats were randomly divided into 7 groups of 6 rats in each and blood glucose was estimated to ascertain group differences, if any. Group 1 was kept as normal control. Remaining 6 groups were induced diabetes by intraperitoneal injection of streptozotocin @ 40 mg/kg body weight. After 72 h, rats with blood glucose value of >200 mg/dl were included in the study (n=6). Treatment protocols were initiated 48 hrs post-confirmation of diabetes and continued for 2 months. Group 1: non-diabetic control, group 2: streptozotocin (40 mg/Kg i/p single dose)-induced diabetic (DM) control, group 3: Insulin treatment (4 U/kg b. wt. subcutaneously once daily), group 4: glimepiride treatment (4 mg/kg b. wt. orally once daily), group 5: Gymnema sylvestre methanolic leaf extract treatment ( 400 mg/kg b.wt. orally once daily), group 6: Insulin + Gymnema sylvestre methanolic leaf extract treatment (once daily) and group 7: glimepiride + Gymnema sylvestre methanolic leaf extract treatment (once daily). Blood glucose, body weights, sero-biochemical parameters, antioxidant profile in liver, kidney, brain and testis, ATPases, glucose 6 phosphate dehydrogenase (G6PD), cytochrome P450 (CYP450) activity and glycogen in liver, electron microscopy and histopathology of various tissues were studied at different time intervals. Also, pharmacokinetic interaction of glimepiride with Gymnema sylvestre extract was assessed. There were significant alterations in blood glucose, body weights and other biochemical parameters in diabetic control group 2 as compared to group 1. All the treated groups revealed significant improvement in all the parameters as compared to group 2, while the combination treatment in groups 6 and 7 was found better as compared to single agent-treated groups 3, 4 and 5. The histological studies revealed marked changes in group 2 in all the organs studied, while groups 3 to 5 revealed moderate changes and groups 6 and 7 revealed either minor changes or no pathologically significant changes. Group 1 was devoid of any histological alterations. The electron microscopy of kidney, pancreas and aorta revealed marked alterations in group 2, while groups 6 and 7 revealed better architecture. The pharmacokinetic study revealed the values of T1/2 (h), Ka (h-1), Ke (h-1) and Tmax (h) of glimepiride were siginificantly varied in Gymnema sylevestre pre-treated rats compared to normal rats administered with glimperide In conclusion, the study revealed that addition of Gymnema sylvestre leaf extract to insulin and glimepiride had positive pharmacodynamic interaction in improving the patho-biochemical alterations due to streptozotocin-induced diabetes mellitus in rats, which was evident from greater improvement in sero-biochemical and organ parameters in the groups that were treated using a combination of Gymnema sylvestre with either insulin or glimepiride as compared to individual agent-treated groups. Important pharmacokinetic parameters did not vary significantly when glimepiride was used in combination with Gymnema sylvestre leaf extract.
Open Access
TOXICODYNAMIC INTERACTION OF LEAD WITH CADMIUM AND THERAPEUTIC EVALUATION OF N-ACETYL L-CYSTEINE IN RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2011-07) ANlL KUMAR, B; GOPALA REDDY, A(MAJOR); RAVl KUMAR, P; MADHAVA RAO, T; ANAND KUMAR, A
ABSTRACT: An experimental study was conducted to evaluate the molecular mechanisms of lead and cadmium toxicity and their toxicodynamic interaction, and to evaluate therapeutic potential of N-Acetyl L-cysteine (NAC) against the toxicity in Wstar rats. After an acclimatization period of 2 weeks, rats were randomly divided into 8 groups comprising of 6 rats in each. Group 1 was kept as normal control throughout the experimental period, 2 was given NAC @ 300 mg per kg body weight administered by oral gavage, 3 was given lead (lead acetate @ I000 ppm in feed), 4 was given cadmium (cadmium chloride @ 300 ppm in feed), 5 was given lead + cadmium as per above doses in feed, 6 was given lead + NAC as per above schedule, 7 was given cadmium + NAC as per above schedule, and group 8 was given lead + cadmium + NAC as per above schedule for 3 months. Body weights, haematology (TEC, TLC, Hb, PCV, MCH and MCHC), activity of 6-ALAD and erythrocytic SOD, sero-biochemical parameters (ALT, CPK, troponins, plasma TBARS and serum creatinine), antioxidant profile (GSH, GST, TBARS and protein carbonyls) in liver, kidney, heart, testis and brain, ATPases and tissue lipids in liver and brain, neurotransmitters (Ach and glutamate) in brain, CYP450, glycogen and G6PD in liver, weight of testes, testicular LDH and sperm count, electron microscopy of kidney in cadmium exposed groups and histopathology of liver, kidney, testis and heart were studied. Also, interaction of lead and cadmium with zinc and copper in liver, kidney, heart, testis and brain was assessed. The present study revealed significant alterations in body weights, haematology, sero-biochemical parameters, antioxidant profile, ATPases, tissue lipid profile, neurotransmitter, CYPd50, glycogen, GGPD, weights of testes, testicular LDH, sperm count, and concentration of zinc and copper in toxic control groups 3, 4 and 5 as compared to control and NAC-treated groups. The toxic combination (Pb + Cd) group 5 showed significant alterations in most of the parameters studied as compared to Pb alone and Cd alone administered groups. All the NAC-treated groups revealed significant improvement in all the parameters. The histological studies of liver, kidney, testis and brain revealed marked changes in toxic control groups, while therapeutic groups revealed mild changes or no pathologically significant changes. Groups 1 and 2 were devoid of any alterations. The electron microscopy of kidney revealed marked alterations in kidney architecture in groups 4 and 5, while groups 7 and 8 revealed better architecture. The results of the investigation revealed that lead, cadmium' and their combination induced toxicity to the biological system due to the excess generation of free radicals and impairment of antioxidant defenses. Toxic effects were more pronounced in the group that received a combination of lead and cadmium suggesting positive toxicodynamic interaction. Use of NAC countered the adverse effects of lead and cadmium induced toxicity to a major extent suggesting its antioxidant potential owing to replenishment of tissue pool of GSH. Further, NAC administration reduced the extent of accumulation of lead and cadmium in various tissues.
Open Access
INTERACTION OF TRIGONELLA FOENUM GRAECUM WITH INSULIN AND GLIMEPIRIDE IN EXPERIMENTAL DIABETES MELLITUS IN RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2011-01) HARITHA, C; GOPALA REDDY, A(MAJOR); SRINIVASA RAO, G; ANJANEYULU, Y; MADHAVA RAO, T; RAMANA REDDY, Y
ABSTRACT: An experimental study was conducted to evaluate the interaction of fenugreek seed powder with insulin and glimepiride in diabetic Sprague dawley rats. Rats were randomly divided into 7 groups of 8 rats in each and blood glucose was estimated to ascertain group differences, if any. Group 1 was kept as normal control. Remaining 6 groups were induced diabetes by intraperitoneal injection of streptozotocin @ 40 mg/kg body weight. After 72 h, rats with blood glucose value of >250 mg/dl were included in the study (n=8). Treatment protocols were initiated from day 2 post-confirmation of diabetes and continued for 8 wks. Group 1: non-diabetic control, group 2: streptozotocin (40 mg/Kg i/p single dose)-induced diabetic (DM) control, group 3: Insulin treatment (4 U/kg once daily), group 4: glimepiride treatment (4 mg/kg orally once daily), group 5: fenugreek seed powder treatment (1 g/kg orally once daily), group 6: Insulin + fenugreek seed powder treatment (once daily) and group 7: glimepiride + fenugreek seed powder treatment (once daily). Blood glucose, body weights, sero-biochemical parameters, antioxidant profile in liver, kidney, brain and testis, ATPases in liver and brain, relative weights of kidney and testes, electron microscopy of kidney and histopathology of various tissues were studied at different time intervals. Also, pharmacokinetic interaction of glimepiride with fenugreek seed powder was assessed. There were significant alterations in blood glucose, body weights and other biochemical parameters in diabetic control group 2 as compared to group 1. All the treated groups revealed significant improvement in all the parameters as compared to group 2, while the combination treatment groups 6 and 7 were found better as compared to single agent-treated groups 3 through 5. The histological studies revealed marked changes in all the organs studied, while groups 3 to 5 revealed moderate changes and groups 6 and 7 revealed either minor changes or no pathologically significant changes. Group 1 was devoid of any alterations. The electron microscopy of kidney revealed marked alterations in kidney architecture in group 2, while groups 6 and 7 revealed better architecture. Fenugreek seed powder treatment increased AUC and elimination half life of glimepiride in combination as compared to glimepiride-alone treated group, while the Cmax and tmax did not vary between groups 4 and 7. The results of the study revealed positive pharmacodynamic interaction between fenugreek and either insulin or glimepiride in improving the patho-biochemical alterations in diabetic rats. Further, there was a favourable pharmacokinetic interaction. Further studies are warranted to estimate P-gp and OATP activities along with CYP2C9 estimation for better understanding of pharmacokinetic interactions of fenugreek and glimepiride in diabetes mellitus.
Open Access
HYDROGENATED VEGETABLE OIL : WHETHER BENEFICIAL OR HARMFUL – AN INSIGHT
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2009-07) ALPHA RAJ, M; GOPALA REDDY, A(MAJOR); ADILAXMAMMA, K; RAJASEKHAR REDDY, A; ANJANEYULU, Y
ABSTRACT : An experimental study was conducted to evaluate the effects of supplementation of high energy high hydrogenated vegetable oil diet in various stressor models. A total of 160 White Leg Horn layers of 18 weeks age were randomly divided into eight groups of 20 birds each. Groups 1, 3, 4 and 5 were maintained on basal diet and groups 2, 6, 7 and 8 on 5% vanaspati supplemented basal diet until the age of 42 weeks. At 42 weeks of age, groups 3 and 6 were treated with 1% ferrous sulphate in the diet, groups 4 and 7 were treated with chlorpyrifos @ 100 ppm and groups 5 and 8 were treated with cadmium @ 100 ppm in the basal diet for a period of 12 weeks. The performance parameters like body weights, weight gains, feed consumption, feed conversion ratio, egg production and egg weight were recorded at monthly intervals. The sero-biochemical analysis of cholesterol, HDL cholesterol, triglycerides, total protein, albumin, globulin, A/G ration, alkaline phosphatase, alanine transaminase and creatinine was carried out at monthly interval. Oxidant and antioxidant status was determined by estimation of TBARS and GSH in serum, liver and kidney, protein carbonyls in serum and vitamin C levels in liver and kidney. The immunological status of the birds was evaluated by HI titre against RD virus in serum and phytohaemagglutinin (PHA) assay at the end of the experimental period. Histopathological studies were conducted on liver, kidney and brain at the end of the experimental period. The ferrous sulphate toxic control revealed significantly (p<0.05) higher FCR, serum creatinine, liver TBARS and phospholipids, and significantly lower egg production compared to normal group. Histopathology revealed congestion and bile duct hyperplasia in liver, intertubular haemorrhage and focal lymphoid aggregates in kidney and no detectable abnormalities in brain. The supplementation of vanaspati along with ferrous sulphate significantly (p<0.05) increased the egg production and serum ALP activity but decreased egg weight, FCR and HI titre compared to toxic control. The histopathology revealed similar changes of more severity besides tubular rearrangement of hepatic cells and degenerative changes in kidney. The CPS toxic control showed significantly (p<0.05) higher egg production, higher serum ALP activities and a non-significantly higher total lipids of liver and lower serum HDL compared to normal group. The histopathology revealed mild fatty changes, congestion and bile duct hyperplasia in liver, degenerative changes in kidney and congestion in brain. Supplementation of vanaspati along with CPS resulted in decreased egg production, decreased egg weight, HI titre but increased PHA index compared to toxic control. The histopathology showed marked fatty changes in liver, haemorrhages in kidney and vacuolation in brain. The cadmium toxic control revealed a significantly (p<0.05) lower body weight, weight gain, egg production and egg weights, but significantly increased the FCR, serum ALP and ALT acitivities, creatinine and TBARS of liver and kidney. The GSH and vitamin C levels of kidney were reduced. Paradoxically, the HDL and HI titre were significantly (p<0.05) increased compared to normal group. The histopathology revealed congestion, lymphoid aggregates and degenerative changes in liver, haemorrhages and congestion in kidney and brain. The supplementation of vanaspati along with cadmium resulted in a significant decrease of liver GSH and decrease of HI titre compared to toxic control. The histopathology revealed similar pathological changes but of more severity along with fibrosis in liver, kidney and brain. The overall effect of vanaspati supplementation revealed significantly (p<0.05) increased egg production and PHA index, and decreased egg weights, FCR, serum cholesterol, albumin, TBARS of liver and kidney, GSH of liver and HI titre compared to basal diet fed group. Thus, it is concluded that ferrous sulphate, chlorpyrifos and cadmium induce biological damage by means of oxidative stress and organ damage. However, cadmium was more potent followed by ferrous sulpahte and chlorpyrifos. After accounting for increased calorie intake, the supplementation of vanaspati was not effective in reducing the toxicity of different stressors and accentuated the toxicity in certain conditions. Further, vanaspati supplementation resulted in abnormal immunological response. In view of the above findings, it is concluded that hydrogenated vegetable oil is harmful and regular use will lead to adverse consequences.
Open Access
ADDITION OF A HERB TO A STATIN: A POSITIVE OR NEGATIVE INTERACTION? EXPERIMENTAL STUDIES ON DYSLIPIDAEMIAS IN RATS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2009-03) DILIP REDDY, GUNTURU; GOPALA REDDY, A(MAJOR); SRINIVASA RAO, G; ANAND KUMAR, A; RAJASEKHAR REDDY, A
ABSTRACT : A total of 56 male Sprague dawley rats of uniform weight and age were randomly divided into seven groups consisting of eight rats in each group after an acclimatization period of 3 weeks to evaluate the interaction of atorvastatin with garlic in induced dyslipidaemia. Group 1 served as plain control, while groups 2 and 3 were fed with high fat and high cholesterol diet throughout the experimental period. Groups 4,5,6 and 7 received 1% (100% dose), 0.5% (50% dose), 0.25% (25% dose) and 0.75% (75% dose) fresh garlic w/w in feed, respectively in addition to the high fat and high cholesterol diet and administered with 10 (100% dose), 5 (100% dose), 7.5 (100% dose) and 2.5 (25% dose) mg/kg atorvastatin respectively, while group 3 served as atorvastatin control, which received 10 mg/kg atorvastatin per day orally for 12 weeks. Blood collection was carried out at every two weeks interval for plasma biochemical analysis of total cholesterol, HDL cholesterol, triglycerides and creatinine and aspartate transaminase (AST). Single dose and multiple dose pharmacokinetic studies were performed at the beginning of the first dose and at the end of last dose of atorvastatin, respectively in groups 3 to 7. At the end of the experiment, liver and kidneys were collected for assay of TBARS, glutathione and SOD. Histological, histochemistry and electron microscopy studies were conducted on different organs at the end. All the treatment groups exhibited significant improvement in dyslipidaemic condition when compared with group 2 from 2nd week of treatment by reducing the TC, TG and LDL-C levels with subsequent increase in HDL-C levels. Group 4 was highly effective in correcting dyslipidaemia due to the synergistic pharmacodynamic actions of herb and drug. Plasma atorvastatin concentrations during multiple dose PK studies were significantly higher than single dose counterparts. PK parameters showed a significant increase in the garlic treated groups with high values of Cmax, AUC, AUMC, MRT and half-life which could be attributed to the inhibitory activity of garlic on drug transporters and metabolizing enzymes. High concentration of the drug in plasma in group 4, 5 and 3 resulted in toxicological manifestations in liver and kidney, which was evident from the increased plasma creatinine concentration, AST activity and oxidative stress. Histopathological studies on liver, kidney revealed moderate to severe damage in groups 4 and 5, which also exhibited mitochondrial damage on transmission electron microscopy. From this study, it can be concluded that garlic and atorvastatin exhibited positive pharmacodynamic interaction in reducing dyslipidaemias. The pharmacokinetic studies revealed that garlic increased the pharmacokinetic parameters and the toxicological studies indicated that high dose of atorvastatin + garlic has negative safety profile. Further studies are warranted to address the pharmacokinetic interactions of statin and garlic in detail.
Open Access
EXPERIMENTAL EVALUATION OF TOXICITY CAUSED BY CADMIUM-INDUCED OXIDATIVE STRESS AND ITS COUNTERACTION BY CERTAIN HERBS AND HERBAL COMBINATIONS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2008-09) Bharavi, K; GOPALA REDDY, A(MAJOR); SRINIVASA RAO, G; Rajasekhar Reddy, A; Rama Rao, S.V
ABSTRACT : A total of 225 male broiler chicks of day old age belonging to Vencobb strain were randomly divided into fifteen groups consisting of fifteen chicks in each group. Group 1 was maintained on basal diet and group 2 on cadmium @ 100 ppm as cadmium chloride (CdCl2) in feed for 42 days (6 wks). Groups 3 to 12 were given cadmium containing diet for the first 4 wks (28 days) and subsequently treated respectively with Withania somnifera, Ocimum sanctum, Asparagus racemosus, Andrographis paniculata, Murraya kienigii, shilajit, Gymnema sylvestra, Allium sativum, Spirulina and ginseng each at 0.1% level in feed till the end of 6th wk, while groups 13 to 15 were given the combination of Spirulina + shilajit + G.sylevestre, W. somnifera + A.racemosus +A.paniculata and W.somnifera + M.koenigii+ A.sativum, respectively. In combinations, each herb was added at 0.05% level in feed for the remaining 2 weeks. The performance parameters were recorded at weekly intervals. Antioxidant defense profile, biomarkers of hepatic damage, renal damage, lipid profile, protein profile and HI titre in serum, and phytohaemagglutinin (PHA) index were estimated at the end of 4th and 6th wk. Histopathological studies and estimation of thiobarbituric acid reactive substances (TBARS), reduced glutahtione (GSH) and superoxide dismutase (SOD) were done at the end of 6th wk. The cadmium treatment resulted in a significant (P<0.05) reduction in body weights, protein profile, GSH (6th week), haemagglutination inhibition (HI) titre and phytohaemagglutination (PHA) index (6th week), while feed conversion ration (FCR), total cholesterol, low density lipoproteins (LDL) cholesterol, triglycerides, TBARS (6th week), SOD, catalase, alanine transaminase (ALT), blood urea nitrogen (BUN) and creatinine were significantly (P<0.05) increased at the end of 4th week in groups 2 to 15 and all these parameters exhibited similar trend at the end of 6th week in group 2 that was maintained with out any treatment. Following the administration of herbs in test in groups 3 to 15, there was a marked improvement in all the above parameters as compared to those of cadmium control group 2 at the end of 6th week. Histological abnormalities were also recorded in the liver, kidney, spleen and bursa fabricius in cadmium control group 2, where as group 1 did not reveal any abnormalities on histopathology, while the treated groups revealed lesions of mild intensity or signs of regeneration. Thus, it is concluded that cadmium induces biological damage by means of oxidative stress and the herbs/herbal combinations in test offered better amelioration. The combinations of herbs found relatively superior as compared to the remaining groups in test
Open Access
LEAD INDUCED OXIDATIVE STRESS IN POULTRY AND ITS AMELIORATION BY CERTAIN ANTIOXIDANTS AND ADAPTOGENS
(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2007-05) RATAN KUMAR, M; SOMASEKHAR REDDY, K(MAJOR); GOPALA REDDY, A; RAJASEKHAR REDDY, A; ANJANEYULU, Y
ABSTRACT : A total of 225 day old sexed male broiler chicks of Vencobb strain were randomly divided into fifteen groups consisting of fifteen chicks in each group. Groups 1,2,3,4 and 5 served as plain controls. Group 1 was maintained on based diet, 2 on poly herbal formulation (PHF) @ 1 g/kg feed, 3 on shilajith @ 100 mg/kg feed, 4 on amla @ 500 mg/kg feed and 5 on vit E (3000 mg/kg feed) + Se (0.3 mg/kg feed). Group 6 was maintained on lead @ 250 mg/kg feed for 42 days (6 weeks) and 7 on lead for 28 days and subsequently on basal diet with out lead for the remaining 2 weeks. Groups 8, 9, 10 and 11 were given lead along with PHF, shilajith, amla and vit E + Se, respectively throughout the experiment for 6 weeks. Groups 12, 13, 14 and 15 were given lead containing diet for the first 4 weeks (28 days) and subsequently treated with PHF, shilajith, amla and vit E + Se, respectively for the remaining 2 weeks. The performance parameters were recorded at weekly intervals. Antioxidant defense profile (GSH-Px, GSH-R and catalase), biomarkers of hepatic damage (ALT and ALP), renal damage (serum creatinine and BUN), lipid profile (total cholesterol, triglycerides, LDL cholesterol and HDL cholesterol) in serum and protein profile (total protein, albumin, globulin, A/G ratio) were estimated at the end of 4th and 6th week. Liver lipids, TBARS and HI titer, and the activity of Na+/k+ ATPase, Mg2+ ATPase, Ca2+ ATPase and CYP450 were estimated at the end of 6th week. Electron microscopy of kidney conducted at the end of 6th week revealed ruptured mitochondria and vacuolation in the proximal convoluted tubules in the toxic control group 6. Prominent lysosomal bodies were also observed along with distraction of brush border and narrowing of lumen. Few lysosomal bodies were found in the groups 13 and 14 (amla and vit E + Se treated groups, respectively), while PHF and shilajith treated groups (12 and 13, respectively) exhibited no specific cellular changes on electron microscopy. Performance parameters, antioxidant defense parameters, enzyme levels, sero-biochemical parameters, activity of membranes ATPases and CYP450 were significantly altered in the toxic control The sero-biochemical and histopathological parameters were normal in controls groups 1 to 5 and other groups that were given the drugs in test and showed good amelioration. Thus, it is concluded that lead induces biological damage by means of oxidative stress and the drugs in test viz., PHF, shilajith, amla and vit E + Se offered better amelioration.

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