Influence of four agents (tibric acid, DH 990, oxandrolone and Sch 9122) on aspects of lipid metabolism in rats)

Abstract

We have investigated the effects of four drugs on aspects of lipid metabolism in rats. The four drugs used were: tibric acid = 2-chloro-5-(cis--3,5-dimethylpiperidonosulfonyl)benzoic acid; DH 990 = 2-[(3,5-di-t-butyl-4-hy-droxyphenyl)thio]hexanoic acid; oxandrolone = 17beta-hydroxyphenyl-17a-methyl-2-oxa-5a-androstan-3-one; and Sch 9122=2-(p-anisyl)-3(2-pyridyl)pentane hydrochloride. Serum and liver triglycerides and liver cholesterol, 7a-hydroxylase and 26-oxidase were determined. Tibric acid (0.015%) was hepatomegalic and hypotriglyceridemic. It did not affect normal 7a-hydroxylase or 26-oxidase activity. In the absence of cytosal, this drug resulted in normal mitochondrial cholesterol-26-oxidase activity whereas none was observed with preparations from control rats. DH 990 (0.075%) did not affect liver size. It had a slight (10--20%) hypolipidemic effect. The effects of DH 990 on the two liver enzymes were similar to those of tibric acid. In view of the absence of a hepatomegalic effect of DH 990, its influence on mitochondrial oxidation of cholesterol in the absence of cytosol is noteworthy. Oxandrolone (0.15%) had a slight (11%) hepatomegalic effect but did not influence serum of liver lipid levels. This drug caused a 19% increase in liver 7a-hydroxylase activity but did not affect cholesterol-26-oxidase activity in the presence or absence of cytosol. Sch 9122 (0.03%) caused significant weight loss. Serum and liver cholesterol levels were unaffected, but serum triglyceride levels were significantly elevated in rats fed this drug. Cholesterol-7a-hydroxylase activity was slightly (11%) higher than normal, but 26-oxidase was significantly lower.