NADPH-dependent inhibition of lipid peroxidation in rat liver microsomes

Biochem Biophys Res Commun. 1992 Jul 15;186(1):74-80. doi: 10.1016/s0006-291x(05)80777-6.

Abstract

Microsomal NADPH-driven electron transport is known to initiate lipid peroxidation by activating oxygen in the presence of iron. This pro-oxidant effect can mask an antioxidant function of NADPH-driven electron transport in microsomes via vitamin E recycling from its phenoxyl radicals formed in the course of peroxidation. To test this hypothesis we studied the effects of NADPH on the endogenous vitamin E content and lipid peroxidation induced in liver microsomes by an oxidation system independent of iron: an azo-initiator of peroxyl radicals, 2,2'-azobis (2,4-dimethylvaleronitrile), (AMVN), in the presence of an iron chelator deferoxamine. We found that under conditions NADPH: (i) inhibited lipid peroxidation; (ii) this inhibitory effect was less pronounced in microsomes from vitamin E-deficient rats than in microsomes from normal rats; (iii) protected vitamin E from oxidative destruction; (iv) reduced chromanoxyl radicals of vitamin E homologue with a 6-carbon side-chain, chromanol-alpha-C-6. Thus NADPH-driven electron transport may function both to initiate and/or inhibit lipid peroxidation in microsomes depending on the availability of transition metal catalysts.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Azo Compounds / pharmacology*
  • Chromans / pharmacology
  • Chromatography, High Pressure Liquid
  • Deferoxamine / pharmacology
  • Kinetics
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / physiology*
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism*
  • Models, Biological
  • NADP / metabolism*
  • NADP / pharmacology
  • Nitriles / pharmacology*
  • Oxidation-Reduction
  • Rats
  • Rats, Inbred Strains
  • Vitamin E / analysis
  • Vitamin E / metabolism*
  • Vitamin E Deficiency / metabolism

Substances

  • Azo Compounds
  • Chromans
  • Nitriles
  • 2,2'-azobis(2,4-dimethylvaleronitrile)
  • Vitamin E
  • NADP
  • 2,2,5,7,8-pentamethyl-1-hydroxychroman
  • Deferoxamine