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2007 - 200912010 - 20111
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Subject: Veterinary Pharmacology and Toxicology × Author: HARITHA, C × Start date: 2000 ×
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    ThesisItemOpen 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.
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    ThesisItemOpen Access
    AN INSIGHT INTO THE TOXICITY OF DICLOFENAC ALONE AND UNDER THE INFLUENCE OF CERTAIN VARIABLES IN BROILERS
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2007-09) HARITHA, C; GOPALA REDDY, A(MAJOR); SOMASEKHAR REDDY, K; ANJANEYULU, Y
    ABSTRACT : A total of 80 sexed male broiler chicks (Cobb strain) of a day old age were procured for the study. The chicks were randomly divided into eight groups consisting of ten in each group. All the birds were provided with feed and water ad libitum throughout the experiment. Group 1 was kept as basal diet control (1-32 days), group 2 on basal diet for 32 days + diclofenac (0.8 mg/kg body weight I/M) on day 24, 26, 28, 30 and 32, group 3 on basal diet for 32 days + cyclophosphamide (50 mg/kg body weight I/M once daily) from day 20 to 23, group 4 on high protein, high calcium, low vitamin A (HPHC) diet (1-32 days), group 5 on basal diet+ diclofenac + cyclophosphamide (as per the schedule), group 6 on HPHC + diclofenac (as per the schedule), group 7 on HPHC + cyclophosphamide (as per the schedule) and group 8 on HPHC + diclofenac+ cyclophosphamide (as per the schedule). Diclofenac in combination with cyclophosphamide (groups 5 and 8) was given after confirming immunosuppression by performing HI and PHA tests. Studies on biomarkers of oxidative stress including antioxidant defenses, sero-biochemical parameters, histopathology and electron microscopy were done after 32 days of experiment. The results revealed a significant (P< 0.05) increase in the activity of TBARS (liver and kidney), SOD, catalase, GGT and ALT, and concentration of BUN, creatinine, total prteins and globulins (blood), while there was a significant (P < 0.05) decrease in the concentration of GSH in liver and kidney, albumin, A/G ratio, PGE2 and immunological profile (blood) in the groups given diclofenac either alone or in combination with other variables. The histological examination of liver, kidney, spleen, bursa and heart revealed lesions of mild to marked severity in different combinations. Visceral gout was prominent in groups 6 and 8. From the findings of the present study, it can be concluded that diclofenac has the toxic potential in poultry at sub-therapeutic doses and further the toxic effects are more pronounced under the influence of immunosuppressants and HPHC diet. These findings on diclofenac confirm the reports on vultures as far as the toxic effects are concerned, though the mortality in poultry is not very high at the dose tested, which may be due to the reason that both these species belong to two separate infraclasses (Eoaves and Neoaves, respectively). This is regarded as one of the deepest phylogenetic branches amongst living birds.