Effect of hypolipidaemic drugs on hepatomegaly and micro-bodies in the rat. A new approach to the nature of hepatic peroxisomal proliferation.
Etofylline clofibrate, a new hypolipidaemic drug of low toxicity, was evaluated for effects of induction of peroxisomal proliferation and hepatomegaly in male rats by comparison with standard hypolipidaemic drugs (bezafibrate, clofibrate, fenofibrate). The dose schedule was selected according to standard toxicological methods in an attempt to determine a dose-dependent relationship with particular reference to a possible "nil effect" dose. At high dose levels (250 mg/kg/day), all test drugs induced proliferation and hepatomegaly. At 50 mg/kg/day, all reference compounds induced proliferation and hepatomegaly while etofylline clofibrate indicated only moderate proliferation and no hepatomegaly. At very low dose levels only standards induced proliferation while etofylline clofibrate neither induced proliferation nor hepatomegaly. The latter was still present in bezafibrate and fenofibrate-treated groups. Results indicated a dose-dependent effect of etofylline clofibrate on both parameters with a "nil effect" dose between 11 and 50 mg/kg. Neither a dose-dependent nor a "nil effect" dose was found with any of the standard drugs. For the most potent peroxisomal proliferators (bezafibrate and clofibrate), numerous large and mis-shapen peroxisomes were found at all dose levels. Hepatic changes in terms of pharmacological and toxicological criteria are discussed with special reference to a proposed drug related toxic effect on liver function.
D000818:Animals; D006529:Hepatomegaly / Q000139:chemically induced; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008830:Microbodies / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats
D000960:Hypolipidemic Agents