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2010 - 20114
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Subject: Veterinary Pharmacology and Toxicology × End date: 2011 × Start date: 2010 × Type: Thesis × Thesis Type: M.V.Sc. ×
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    A STUDY ON THE TERATOGENIC EFFECTS AND ORGAN TOXICITY OF NIMESULIDE AT DIFFERENT DOSE LEVELS IN PREGNANT AND PROGENY RATS
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2011-10) SWAPNIL VIJAYKUMAR JINTPURE; USHA RANI, M(MAJOR); GOPALA REDDY, A; ANJANEYULU, Y
    ABSTRACT: The present study was aimed to evaluate the teratogenic effects and organ toxicity in the dams and their progeny treated with nimesulide in gestation period at different dose levels. Seventy two female albino rats of Sprague dawley strain were divided into 3 groups and treated as follows. Group 1 served as control, group 2 received nimesulide @ 20 mg/kg body weight and group 3 received nimesulide @ 60 mg/kg body weight via intramuscular route from day 7th to 17th day of gestation. In each group, half of the pregnant rats were subjected to caessarian section on 19th day of gestation (caessarian group namely “A”) and the remaining half of the pregnant rats were allowed for normal parturition (normal parturition group namely “B”). Average body weights were recorded at weekly intervals in dams of caessarian, normal parturition group and in progeny of normal parturition group up to weaning day. On 19th day, half of pregnant dams in each groups were subjected to caessarian for uterine weights with progeny, resorption sites, inborn progeny body weight, litter size, live and dead numbers, male: female progeny numbers, skeletal staining of progeny with Alizarin-Red S, Alcian blue-Alizarin Red S stains and soft tissue developmental anomalies. The remaining half, allowed for normal parturition and recorded inborn progeny body weights, litter size, live-dead numbers, male: female progeny numbers and other abnormalities, if any. Serum biochemical profiles (Albumin, ALP, ALT, AST, BUN, creatinine, GGT and total protein) were recorded on 19th day of gestation in dams of caessarian group and the same serum biochemical profiles and haematology (RBC, WBC and haemoglobin) was recorded on post natal day 21 in progeny of normal parturition group. TBARS and GSH were estimated on 19th day in liver and kidney homogenates. Histopathology of kidney, liver, stomach and ovary were studied in dams of caessarian group on 19th day and liver, kidney and heart in progeny of normal parturition group on weaning day. The study showed no evidence of teratogenicity by skeletal staining, uterine weights with progeny, resorption sites, litter size, inborn progeny body weights, male: female progeny numbers, live and dead numbers, and weekly body weights in progeny upto weaning. There was a significant difference in serum biochemical profiles of dams and was more evident in nimesulide treated at 60 mg/kg body weight. Further, there was no significant difference in the haematological parameters and serum biochemical profiles of progeny except an increase in BUN and creatinine, which was more evident in group 3 as compared to groups 2 and 1. Treatment with nimesulide at higher dose induced oxidative stress and tissue damage of liver and kidney as evident from increased levels of MDA and decreased levels of GSH, histopathology of liver, kidney and stomach of dams and kidney of progeny of normal parturition group. It is concluded that nimesulide at 60 mg/kg body weight in pregnant dams showed more significant damage to liver and kidney as from light microscopic findings of liver, kidney, stomach and ovary as compared to the dose of 20 mg/kg body weight and control.
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    ThesisItemOpen Access
    PROTECTIVE EFFECT OF VITAMIN E IN DOXORUBICIN-INDUCED TOXICITY IN RATS
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2010-08) SHIVAKUMAR, P; USHA RANI, M(MAJOR); GOPALA REDDY, A; ANJANEYULU, Y
    ABSTRACT: The present study was aimed to evaluate the protective effect of vitamin E in doxorubicin-induced toxicity in rats, which were divided into 4 groups and treated as follows: Group 1: sham control, 2: doxorubicin control, 3: doxorubicin + vit-E @150 mg/kg b. wt and 4: doxorubicin + vit-E @ 500 mg/kg b. wt Average body weights were recorded at weekly intervals and organ weights were recorded at the time of sacrifice. On 28th day, organs were collected for estimation of TBARS, protein carbonyls and GSH in tissue homogenates. Activity of Na+-K+ ATPase , Mg2+ATPase and CYP450 of liver, intra-testicular LDH, serum troponins, creatinine, LDH and AST were also estimated, besides haematology at the end of experiment on 28th day. Histopathology of heart, liver, kidney and testes was also studied at the end. Body weight gain, relative organ weight, RBC, WBC, Hb, PCV, GSH, CYP450, Na+/K+ ATPase and Mg2+ATPase were significantly (P < 0.05) decreased in doxorubicin group, while TBARS, protein carbonyls, serum LDH, intra-testicular LDH, serum AST, creatinine and serum troponins were significantly (P < 0.05) increased in group 2. Group 1 did not reveal any abnormalities on histopathology. Group 2 (doxorubicin) showed marked congestion and degenerative changes in heart, kidney, liver and testis. Vitamin E-treated groups (3 and 4) showed improvement in all the parameters studied, though it was marked with vitamin E @ 500 mg/Kg. From this study, it is concluded that doxorubicin induces toxicity to heart, kidney, liver and testes, and these effects can be reverted by vitamin –E administration in a dose-dependent manner.
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    ThesisItemOpen Access
    PROTECTIVE EFFECT OF N-ACETYL CYSTEINE AGAINST ARSENIC-INDUCED TOXICITY IN RATS
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2010-06) HEMALATHA, P; GOPALA REDDY, A(MAJOR); USHA RANI, M; ANAND KUMAR, A; RAMANA REDDY, Y
    ABSTRACT: N-acetyl cysteine was evaluated against arsenic-induced toxicity in rats. The Wistar rats were divided into 4 groups and treated as follows: Group 1: sham control, 2: arsenic control, 3: N-Acetyl cysteine (NAC) pre-treatment for two weeks followed by arsenic + NAC and 4: arsenic + NAC. Average body weights were recorded at weekly intervals and testes weights were recorded at the time of sacrifice. On 29th day, organs were collected for estimation of TBARS, protein carbonyls and GSH in tissue homogenates. Activity of Na+-K+ ATPase , Mg2+ATPase and CYP450 of liver, intra-testicular LDH, serum creatinine, and serum LDH were also estimated. Histopathology of heart, liver, kidney, testis, lung, intestine and stomach was also studied at the end. Body weight gain, relative testis weight, GSH, CYP450, Na+/K+ ATPase and Mg2+ATPase were significantly (P < 0.05) decreased, while TBARS, protein carbonyls, serum LDH, intra-testicular LDH and serum creatinine were significantly (P < 0.05) increased in group 2 as compared to other groups. Group 1 did not reveal any abnormalities on histopathology. Group 2 (arsenic control) showed marked degenerative changes in heart, kidney, liver, testis, lung, intestine and stomach. NAC-treated groups (3 and 4) showed improvement in all the parameters studied, though it was marked with NAC pre-treatment. From this study, it is concluded that arsenic induces toxicity to heart, kidney, liver, testis, lung, intestine and stomach, and these effects can be reverted by NAC administration.
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    ThesisItemOpen Access
    STUDIES ON THE EFFECT OF MORIN, A CYP 2C9 AND CYP3A4 INHIBITING FLAVONOID ON THE PHARMACOKINETICS OF MELOXICAM IN RABBITS
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI – 517 502. (A.P) INDIA, 2010-12) SESHAIAH V, PAMULAPATI; SRINIVASA RAO, G (Major); BHARAVI, K; ANAND KUMAR, P
    ABSTARCT: Meloxicam is a novel non-steroidal anti-inflammatory drug with selectivity towards cyclo-oxygenase 2 (COX-2) compared to COX-1. It is extensively metabolized in the liver, primarily by polymorphic cytochrome P450 2C9 (CYP2C9) enzyme, and to a minor extent by CYP3A4 enzyme, to four pharmacologically inactive metabolites and only negligible amounts of the parent drug are found in urine and feces. The effect of morin, a flavonoid known to be dual inhibitor of CYP2C9 and CYP3A4 on the plasma concentrations and pharmacokinetics of meloxicam was studied in male rabbits in the present study in three phases. In phase I, meloxicam alone was administered orally at a dose rate of 1.5 mg.kg-1 whereas in phase II and III the rabbits were given morin by oral route at 10 and 20 mg.kg-1, respectively 30 min before oral administration of meloxicam (1.5 mg.kg-1). Blood was collected at predetermined time intervals by marginal ear vein into heparinized tubes and plasma was separated immediately after blood collection by centrifugation. Meloxicam concentrations in plasma were determined by a validated HPLC method. Pharmacokinetic parameters were calculated by non compartmental technique. In the control group (phase I) where no pretreatment was carried out before the single oral bolus administration of meloxicam (1.5 mg.kg-1), meloxicam was detectable up to 24 h, with the Cmax (Mean±SE, 1.006±0.19 μg.ml-1) at 5.6±0.97 h. The important pharmacokinetic parameters of meloxicam after single oral bolus administration were : β, 0.086±0.11 h-1; t½β, 8.960±1.63 h; AUC0-∞, 12.256±0.91 μg.h.mL-1 ; AUMC0-∞, 167.923±10 μg.h 2.mL-1; Vdss, 1.85±0.4 L.kg-1; ClB, 0.13±0.01 L.kg-1.h -1; and MRT, 14.14±1.66 h. Morin (10mg.kg-1, PO) was given 30 min before administration of meloxicam (1.5mg.kg-1,PO) as pretreatment to rabbits in phase II. The mean value of Cmax obtained was 0.86±0.06 μg.mL-1, which was not significantly low from the control group (phase I). The important pharmacokinetic parameters of meloxicam obtained were : β, 0.082±0.01 h-1; t½β, 8.87±0.99 h; AUC0-∞, 13.16±0.3 μg.h.mL-1; AUMC0-∞, 188.33±17.51 μg.h 2.mL-1; Vdss, 1.62±0.13 L.kg-1; ClB, 0.11±0.0 L.kg-1.h -1; and MRT, 14.27±1.2 h. Upon morin pretreatment prior to meloxicam administration pharmacokinetic parameters such as AUC0-∞, ClB , t½β, Vdss and MRT did not increase significantly from the control group (phase I). In the phase III Morin was given at the dose rate of (20.mg.kg-1, PO) 30 min before administration meloxicam (1.5mg.kg-1,PO). The mean value of Cmax obtained in this phase was 1.39±0.07 μg.mL-1, which was significantly higher from the control group (phase I). There was a significant increase in plasma concentrations of meloxicam at all time points in phase III rabbits when compared to control group of rabbits in phase I after administration of meloxicam. The important pharmacokinetic parameters of meloxicam were : β, 0.09±0.01 h-1; t½β 8.78±1.17 h; AUC0-∞, 21.88±0.30 μg.h.mL-1; AUMC0-∞, 306.25±32.9 μg.h 2.mL-1; Vdss, 0.95±0.08 L.kg-1; ClB, 0.07±0.0 L.kg-1.h -1and MRT 13.95±1.34 h. Upon morin pretreatment at 20 mg.kg-1 prior to meloxicam administration pharmacokinetic parameters such as AUC0-∞, and ClB, were altered significantly from the control group (phaseI).