Inhibition of liver microsomal lipid peroxidation by 13-cis-retinoic acid.
The effects of 13-cis-retinoic acid on iron/ascorbate-dependent lipid peroxidation were investigated with rat liver microsomes. 13-cis-retinoic acid effectively inhibited malondialdehyde generation and molecular oxygen consumption associated with lipid peroxidation. Under the conditions employed, inhibition was complete at concentrations as low as 25 microM and the IC50 was 10 microM. Evidence for concomitant retinoid oxidation by microsomal unsaturated fatty acid-derived peroxyl radicals was demonstrated by detection of several retinoid-derived metabolites, including 5,8-oxy-13-cis-retinoic acid, generated during lipid peroxidation. The data indicate that 13-cis-retinoic acid inhibits lipid peroxidation by scavenging lipid peroxyl radicals with its conjugated polyene system. Its antioxidant properties may contribute to the pharmacological activities of this and related retinoids.
Samokyszyn
V M
VM
Department of Chemistry, Wayne State University, Detroit, MI 48202.
Marnett
L J
LJ
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D005290:Ferric Compounds / Q000378:metabolism; D016166:Free Radical Scavengers; D015474:Isotretinoin / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008315:Malondialdehyde / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats
D005290:Ferric Compounds; D016166:Free Radical Scavengers; D008315:Malondialdehyde; D000244:Adenosine Diphosphate; D015474:Isotretinoin; D001205:Ascorbic Acid