Inhibition of lipid peroxidation by a novel compound (CV-2619) in brain mitochondria and mode of action of the inhibition.
Lipid peroxidation in rat brain mitochondria was induced by NADH in the presence of ADP and FeCl3. CV-2619 inhibited the lipid peroxidation in a concentration-dependent manner; the concentration giving 50% inhibition (IC50) was 84 microM. In addition, the inhibitory effect of CV-2619 was strongly enhanced by adding substrates of mitochondrial respiration; when succinate, glutamate, or succinate plus glutamate was added, the IC50 of CV-2619 was changed to 1.1, 10, or 0.5 microM, respectively. Metabolites of CV-2619 also inhibited the lipid peroxidation. The inhibitory effect of CV-2619 on mitochondrial lipid peroxidation disappeared when TTFA, an inhibitor of complex II in mitochondrial respiratory chain, was added. The results indicate that in mitochondria CV-2619 is changed to its reduced form which inhibits lipid peroxidation.
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D016227:Benzoquinones; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003067:Coenzymes; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010205:Pantothenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012402:Rotenone / Q000494:pharmacology; D013804:Thenoyltrifluoroacetone / Q000494:pharmacology; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D016227:Benzoquinones; D003067:Coenzymes; D008054:Lipid Peroxides; D011809:Quinones; D012402:Rotenone; D009243:NAD; D014451:Ubiquinone; D014810:Vitamin E; C016030:pantogab; D010205:Pantothenic Acid; D013804:Thenoyltrifluoroacetone; D005680:gamma-Aminobutyric Acid; D000968:Antimycin A; C024989:coenzyme Q10; C036619:idebenone