Peroxisomal fatty acid oxidation is selectively inhibited by phenothiazines in isolated hepatocytes.
The production of hydrogen peroxide by isolated hepatocytes in response to lauric, palmitic and oleic acids, a measurement of peroxisomal fatty acid oxidation, is inhibited by phenothiazines under conditions in which ketone body production, a measurement of mitochondrial fatty acid oxidation, does not reveal inhibition of mitochondrial activity. This novel finding provides a pharmacological tool for the study of peroxisomal function in whole cells. The mechanism of this effect of phenothiazines, detected in hepatocytes from rats treated with a peroxisome proliferation inducing drug, is not yet known.
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007657:Ketone Bodies / Q000096:biosynthesis; D007850:Lauric Acids / Q000378:metabolism; D008099:Liver / Q000648:ultrastructure*; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010640:Phenothiazines / Q000494:pharmacology*; D051381:Rats
D005227:Fatty Acids; D007657:Ketone Bodies; D007850:Lauric Acids; D009829:Oleic Acids; D010169:Palmitic Acids; D010640:Phenothiazines; C030358:lauric acid; D019301:Oleic Acid; D019308:Palmitic Acid; D006861:Hydrogen Peroxide; D002746:Chlorpromazine