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Subject: Veterinary Pharmacology and Toxicology × End date: 2009 × Start date: 2009 × Thesis Type: Ph.D ×
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    ThesisItemOpen 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.
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    ThesisItemOpen 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.