Hepatic effect of two hypolipidemic drugs in rats

Some hepatic effects of the hypolipidemic agents 3,9-di-3-pyridyl-2,4,8,10-tetraoxaspiro-5,5-undecane (compound A) and 2-(4-dibenzofuranyloxy)-2-methylpropionic acid (compound B) were investigated in male rats. The animals were treated orally with these drugs and a reference compound-clofibrate for 10 weeks, the daily doses being 250, 300 and 300 mg/kg body weight respectively. All three drugs caused hepatomegaly with a normal microscopic appearance in liver cells. In rats given compound A, part of some liver cells could be occupied by numerous membranes of smooth endoplasmic reticulum. The hepatocytes of the rats treated with compound B or clofibrate showed a marked increase in microbody profiles and an elevated hepatic catalase activity in comparison to the control animals. Neither the microbodies nor the catalase activity were affected by compound A. Hypolipidemic effects were demonstrated with all three compounds, the most potent activity being shown by compound B. Treatment with this agent resulted in significantly higher catalse activity than with clofibrate.