Subacute toxicopathological studies of tamoxifen in Wistar rats

The present research work was conducted in 24 male and 24 female Wistar rats to study the toxicoathological effects of repeated dose (28 days) of tamoxifen. Wistar rats were randomly divided into four different groups with six males and six females in each group. Animals of group II to IV were given 1, 10 and 20 mg/kg b.wt tamoxifen respectively by oral gavage for 28 days where as group I was administrated only 0.5% carboxymethylcellulose (vehicle) as control. After completion of 28 days treatment, blood samples were collected for hematology and serum biochemical analysis from retro-orbital plexus with the help of capillary tube. The animals were sacrificed on 29^th day and necropsy examination was performed. Symptoms like weakness, loss of appetite, aggressiveness and mild alopecia were noticed in rats of high dose group. A dose dependant significant rise in mean values of AST and ALT were observed in group III and group IV whereas the mean values of AKP, creatinine and BUN were increased significantly in the group IV. All the rats exposed to tamoxifen at three different dose levels revealed dose dependant pathological changes in group III and IV in different organs. The lesions were characterized by degeneration, necrosis, inflammatory and vascular changes in liver, testes and uterus, which suggested that tamoxifen was hepatotoxic as well as toxic to reproductive system.