USHA RANI, M(MAJOR)GOPALA REDDY, AANJANEYULU, YSWAPNIL VIJAYKUMAR JINTPURE2018-11-142018-11-142011-10http://krishikosh.egranth.ac.in/handle/1/5810083432THESESABSTRACT: 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.ennullThesis