[Comparative biochemical and ultrastructural study of the hepatic response induced in the rat by 2 hypolipemic agents: clofibrate and itanoxone].
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.
D000818:Animals; D002090:Butyrophenones / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D002994:Clofibrate / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002090:Butyrophenones; D000960:Hypolipidemic Agents; C024140:itanoxone; D002784:Cholesterol; D002994:Clofibrate
Etude comparative biochimique et ultrastructurale de la réponse hépatique induite chez le rat par deux agents hypolipémiants: clofibrate et itanoxone.