Naochika Matsunuma

Age-related changes in the susceptibility to clofibric acid, a hypolipidemic agent, of male rat liver.

Age-related changes in the susceptibility to clofibric acid were investigated in male F344 rats of 8, 52, and 117 weeks old. Hepatomegaly, decrease of serum total cholesterol and triglyceride, increase of the total cytochrome P-450 contents, induction of the activities of microsomal omega-hydroxylation and peroxisomal beta-oxidation, proliferation of smooth endoplasmic reticulum and peroxisomes were detected in 8- and 52-week-old rats. In 117-week-old rats clofibric acid treatment resulted in decrease of serum total cholesterol, elevation of the activities of microsomal and peroxisomal enzymes, and slight proliferation of peroxisomes. These results suggest that the susceptibility of the male F344 rat liver to clofibric acid decreases in 117-week-old rats, though the effect is still recognizable.

Strain difference in the susceptibility to clofibrate in male rats

Abstract Difference among strains in the susceptibility to clofibrate in male rats was clarified. Males of three rat strains (F344, Sprague Dawley (SD), and Wistar Lewis) were treated with clofibrate mixed in the diet for 14 days. Both biochemical analysis (measurement of cytochrome P450 content, alkoxycoumarin O-dealkylation, carnitine acetyltransferase activity, peroxisomal β-oxidation, and catalase activity) and morphological analysis (electron microscopy and morphometry of peroxisomes) proved the strain difference. Although the changes caused by clofibrate administration were detected in all strains, the degree of these changes was variable among different strains. The most responsive rat strain was Wistar Lewis, while SD was the least responsive.