Effect of gossypol on hepatic and serum gamma-glutamyltransferase activity in rats

A single intraperitoneal dose (25 mg/kg) of gossypol given to male Sprague-Dawley rats caused marked changes in the activity of the hepatic and serum gamma-glutamyltransferase (GGT) and microsomal monooxygenases. The GGT activity in liver homogenate, S-9 supernatant fraction and microsomes was significantly depressed; however, the level of serum GGT was elevated. While the hepatic glutathione concentration was not greatly changed, the aminopyrine N-demethylase activity and microsomal cytochrome P450 content of the liver were significantly decreased in the treated rats. At necropsy, the livers of the treated rats appeared generally pale with distinct pinpoint foci. Histopathological examination of the liver showed degenerative changes and coagulative necrosis. The results indicate that gossypol is a strong hepatotoxic agent which can produce severe hepatic damage.