Massive liver enlargement accompanied by decreased drug metabolism. Effect of anterior pituitary extract on hepatic ultrastructure, zoxazolamine paralysis, and metabolism in the rat

Abstract

The relationship between liver enlargement and drug metabolism was investigated in female rats. Hepatomegaly (e.g., 31% increase in liver weight in a 17-day experiment) was induced by injection of lyophylized anterior pituitary (LAP) extract The liver enlargement seemed to be due to an increase in the number and the size (enhanced water content and PAS-positive material) of hepatocytes. Electron microscopic examination of the liver revealed slight proliferation of the smooth endoplasmic reticulum and pronounced fragmentation and dilation of the rough endoplasmic reticulum. Zoxazolamine paralysis time was significantly prolonged (+55% and +102%) after 4 and 17 days, respectively, of treatment with LAP. Metabolism of zoxazolamine by the 9000 g supernatant fraction of the liver of rats given LAP for 17 days was reduced by 73%. Thus, the marked hepatomegaly induced by LAP was associated with a prolonged action of the drug which may result from a decrease in hepatic drug metabolism.