Induction of rat hepatic long-chain acyl-CoA hydrolases by various peroxisome proliferators.
Induction of cytosolic long-chain acyl-CoA hydrolases was investigated in rat liver after administration of various peroxisome proliferators and related compounds. Treatment of rats with di-(2-ethylhexyl)-phthalate, di-(2-ethylhexyl)-adipate or tiadenol induced hydrolases I and II, while acetylsalicylic acid induced only hydrolase II. Among the various phenoxyacetic acid derivatives and related compounds, 2,4,5-trichlorophenoxyacetic acid, 2-(4-chlorophenoxy)-2-methylacetic acid, 2-(2-chlorophenoxy)-2-methylpropionic acid and clofibric acid induced both hydrolases I and II, whereas 2, 4-dichlorophenoxyacetic acid induced only hydrolase II. All nine of the above-mentioned inducers also markedly increased the activity of peroxisomal beta-oxidation. Other compounds tested (2-chlorophenoxyacetic acid, 4-chlorophenoxyacetic acid, 4-chlorophenol, phenoxyacetic acid and phenoxy-2-methylacetic acid) were ineffective as inducers. These results suggest that inducers of acyl-CoA hydrolase II also enhance peroxisomal beta-oxidation activity, but do not necessarily induce acyl-CoA hydrolase I. The structure-inducing activity relationships of these compounds are discussed.
D000272:Adipates / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002995:Clofibric Acid / Q000494:pharmacology; D004051:Diethylhexyl Phthalate / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005233:Fatty Alcohols / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D010170:Palmitoyl-CoA Hydrolase / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013869:Thiolester Hydrolases / Q000096:biosynthesis*
D000272:Adipates; D005233:Fatty Alcohols; C004568:tiadenol; C013966:dioctyl adipate; D002995:Clofibric Acid; D004051:Diethylhexyl Phthalate; D013869:Thiolester Hydrolases; D010170:Palmitoyl-CoA Hydrolase