A comparative biochemical and ultrastructural investigation o hepatic response induced in rats by
clofibrate and
itanoxone, a new hypolipemic agent, was performed. Normocholesterolemic Sprague-Dawley male rats were distributed into homogeneous groups and orally treated on 10 successive days either by the vehicle alone (1%--
carboxymethylcellulose), or by
clofibrate (300 mg/kg/day) or by
itanoxone (100 and 300 mg/kg/day). On the eleventh day, a last dose was applied after about 16 hours fasting, one hour before sacrificing the animals. Biochemical parameters (total serum
cholesterol, hepatic
catalase activity) and morphological ones (liver weight, ultrastructural analysis of the hepatic cell with especially cytochemical evaluation and counting of peroxisomes) were studied. The treatment with
clofibrate gave the following results: fall in total serum
cholesterol (-25%), increase in liver weight (+89%) and hepatic
catalase activity (+69%), high proliferation of hepatic peroxisomes (+246%). These data are in agreement with literature. The following observations were noted with
itanoxone: a decrease in total serum
cholesterol proportional to the dose applied and of higher intensity as compared to
clofibrate (-36,5% at 100 mg/kg; -54% at 300 mg/kg), a moderate increase in liver weight (+25% at 100 mg/kg; +41% at 300 mg/kg) and hepatic peroxisomes (+12% at 100 mg/kg; +85% at 300 mg/kg), no effect on hepatic
catalase activity. The moderate feature of the hepatic response induced by
itanoxone in spite of a marked hypocholesterolemic activity was discussed: first in connection with the hypothesis about a relation between the proliferation of hepatic peroxisomes induced by many hypolipemic agents and the advent of
tumors in rats, then, in connection with the association sometimes assumed between the increased number of hepatic peroxisomes and the effect on
lipids of several hypolipemic substances related or not to
clofibrate.