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Inhibition of lipid peroxidation by a novel compound (CV-2619) in brain mitochondria and mode of action of the inhibition

Authors
  • Suno, Masahiro
  • Nagaoka, Akinobu
Type
Published Article
Journal
Biochemical and Biophysical Research Communications
Publication Date
Jan 01, 1984
Volume
125
Issue
3
Pages
1046–1052
Identifiers
DOI: 10.1016/0006-291X(84)91389-5
Source
Elsevier
Keywords
License
Unknown

Abstract

Lipid peroxidation in rat brain mitochondria was induced by NADH in the presence of ADP and FeCl 3. CV-2619 inhibited the lipid peroxidation in a concentration-dependent manner; the concentration giving 50% inhibition (IC50) was 84 μM. 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 μM, 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.

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