Effect of hypolipidemic drugs gemfibrozil, ciprofibrate, and clofibric acid on peroxisomal beta-oxidation in primary cultures of rainbow trout hepatocytes.
Primary cultures of hepatocytes were established from sexually mature male rainbow trout (Oncorhyncus mykiss) and treated with the hypolipidemic drugs gemfibrozil (0.25-1.25 mM), clofibric acid (2.25-3.00 mM), or ciprofibrate (0.25-1.00 mM). Significant dose-related increases in peroxisomal fatty acyl-CoA oxidase (FACO) were seen after exposure for 48 hr to clofibric acid (P < 0.01) and ciprofibrate (P < 0.05) but not gemfibrozil (P = 0.08). Strong correlation was obtained between increased acyl-CoA oxidase activity and the relative amount of peroxisomal bifunctional enzyme (PBE), further supporting evidence of a proliferative effect. These preliminary studies demonstrate that peroxisomal beta-oxidation can be induced in vitro in a primary rainbow trout hepatocyte system.
Donohue
M
M
Environmental Health Sciences Program, School of Public Health, University of Massachusetts, Amherst 01003.
Baldwin
L A
LA
Leonard
D A
DA
Kostecki
P T
PT
Calabrese
E J
EJ
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000187:drug effects / Q000378:metabolism; D042962:Acyl-CoA Oxidase; D000818:Animals; D002478:Cells, Cultured; D002994:Clofibrate / Q000494:pharmacology; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D004746:Enoyl-CoA Hydratase / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D058607:Fibric Acids; D015248:Gemfibrozil / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007535:Isomerases / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000187:drug effects / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000187:drug effects / Q000378:metabolism; D063994:Peroxisomal Bifunctional Enzyme
D058607:Fibric Acids; D000960:Hypolipidemic Agents; D009097:Multienzyme Complexes; D002995:Clofibric Acid; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D015094:3-Hydroxyacyl CoA Dehydrogenases; D042962:Acyl-CoA Oxidase; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases; C019304:ciprofibrate; D002994:Clofibrate; D015248:Gemfibrozil