The American journal of pathology
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Male Swiss-Webster mice were fed diets containing four hypolipidemic agents which are known to induce proliferation of hepatic peroxisomes. Treatment with all four drugs (clofibrate; its structural analogue, nafenopin; and two drugs structurally unrelated to clofibrate, tibric acid and Wy-14,643) produced a marked hepatomegaly in the mice. The extent of the increase in liver weight correlated well with the increases in total hepatic DNA and in the collective volume of hepatocyte peroxisomes. ⋯ Activity of the latter enzyme, however, is not known to be associated with peroxisome fractions. Concomitant administration of actinomycin D or cycloheximide with a single oral dose of clofibrate diminished the increases in liver weight and carnitine acyltransferase which occurred with clofibrate treatment alone. The finding that the major increase in activity of peroxisome enzymes occurred in those associated with metabolism of acyl CoA groups supports the hypothesis that the hypolipidemic action of the drugs and the proliferation of hepatic peroxisomes are related functions.