Effect of the antilipolytic compound acipimox on peroxisome marker enzymes, lipid pattern and biotransformation related functions in rat liver.
The antilipolytic drug acipimox (5-methylpyrazine-2-carboxylic acid 4-oxide) was given to male rats for 1 week at 500, 1000 and 2000 mg/kg/day and for 2, 6 and 7 months at 20, 100 and 500 mg/kg/day. The peroxisome proliferative effect was evaluated determining the activity of catalase and carnitine acetyltransferase, the rate of cyanide-insensitive palmitoyl CoA oxidation and the electrophoretic profile of liver polypeptides. Hepatic lipid content and distribution were evaluated after 2 and 6 months' treatment. The effect on liver detoxificating function was evaluated by assaying glutathione, cytochrome P-450, glutathione-S-transferase and glutathione-reductase activities after 7 months' treatment. Sub-acute and chronic treatment with a wide range of acipimox doses did not cause hepatomegaly, liver peroxisome proliferation or liver steatosis and did not change some important biochemical variables related to detoxification and biotransformation mechanisms. Acipimox given to rats does not have the negative side-effects of other compounds and seems a safe blood lipid lowering drug.
D000818:Animals; D001711:Biotransformation; D002994:Clofibrate / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004798:Enzymes / Q000032:analysis*; D005978:Glutathione / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000032:analysis*; D008970:Molecular Weight; D011506:Proteins / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats
D004798:Enzymes; D000960:Hypolipidemic Agents; D011506:Proteins; D011719:Pyrazines; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione; D002994:Clofibrate; C027696:acipimox