Peroxisome enzyme modification and oxidative stress in rat by hypolipidemic and antiinflammatory drugs.
Changes in the activities of two peroxisomal enzymes (catalase and thiolase), some parameters related to oxidative situations, such as conjugated dienes, zinc, iron, copper and superoxide dismutase after the administration of two known peroxisome proliferators (clofibrate and acetylsalicylic acid), and two drugs pharmacologically related to the former (probucol and diflunisal) have been studied in male Wistar rats. Administration of the drugs was made by p.o. for 15 days. After the treatment the rats were killed, their livers and brains were taken out, and their blood was collected. Peroxisomes were purified by differential centrifugation followed by ultracentrifugation. Total RNA was also extracted and the acyl CoA oxidase mRNA expression was studied. Clofibrate was inactive on both enzymes studied in liver and diflunisal in brain. However, the acyl CoA oxidase mRNA expression increased by clofibrate treatment. Results are justified by the liposolubility and protein-binding properties of the drugs. Otherwise, the present results show the existence of an increased lipid peroxidation, lower value of superoxide dismutase, and variable results for zinc, copper and iron trace elements. These data evidence an oxidative stress situation in plasma of rats treated with these drugs, probably as a consequence of an increase in some beta-oxidation enzymes, which brings about an overproduction of H2O2.
Rivero
A
A
Laboratorio de Bioquímica, Clínica Universitaria de Navarra, Pamplona, Spain.
Monreal
J I
JI
Gil
M J
MJ
D000101:Acetyl-CoA C-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D042962:Acyl-CoA Oxidase; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001483:Base Sequence; D001921:Brain / Q000187:drug effects; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D002994:Clofibrate / Q000494:pharmacology; D004061:Diflunisal / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology*; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000187:drug effects / Q000235:genetics; D011341:Probucol / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood; D015032:Zinc / Q000097:blood
D000893:Anti-Inflammatory Agents; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D004061:Diflunisal; D010088:Oxidoreductases; D002374:Catalase; D013482:Superoxide Dismutase; D042962:Acyl-CoA Oxidase; D000101:Acetyl-CoA C-Acetyltransferase; D002994:Clofibrate; D015032:Zinc; D011341:Probucol; D001241:Aspirin