Lack of stereoselectivity in rat liver peroxisomal enzyme induction by optically active phenoxyacetic acids.
To ascertain if there is stereoselectivity in peroxisomal proliferation induced by chiral peroxisome proliferators, induction by stereoisomers of 2-methyl-4'-chlorophenoxyacetic acid and 2-methyl-2-(2'-4'-dichlorophenoxy)acetic acid were studied in rat in vivo and in vitro with isolated rat hepatocytes. No significant differences in the inducing potencies of the stereoisomers of the above two phenoxyacetic acid derivatives were found for cyanide-insensitive fatty acyl-CoA oxidizing system, fatty acyl-CoA oxidase, carnitine acetyltransferase or carnitine palmitoyltransferase. There was also no significant difference in the degree of hepatomegaly or lipid-lowering effect between the isomers. The findings with cultured rat hepatocytes agreed with those of the studies in vivo.
Koibuchi
Y
Y
Department of Clinical Biochemistry, Tokyo College of Pharmacy, Japan.
Yamada
J
J
Watanabe
T
T
Suga
T
T
D015084:2,4-Dichlorophenoxyacetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008456:2-Methyl-4-chlorophenoxyacetic Acid / Q000494:pharmacology*; D000214:Acyl Coenzyme A / Q000378:metabolism; D042962:Acyl-CoA Oxidase; D000818:Animals; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D000214:Acyl Coenzyme A; D015084:2,4-Dichlorophenoxyacetic Acid; D008456:2-Methyl-4-chlorophenoxyacetic Acid; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase; D002334:Carnitine O-Palmitoyltransferase; D002332:Carnitine O-Acetyltransferase; C010571:dichlorprop