NADPH-dependent inhibition of lipid peroxidation in rat liver microsomes.
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.
Kagan
V E
VE
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Serbinova
E A
EA
Safadi
A
A
Catudioc
J D
JD
Packer
L
L
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003676:Deferoxamine / Q000494:pharmacology; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D009249:NADP / Q000378:metabolism* / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000032:analysis / Q000378:metabolism*; D014811:Vitamin E Deficiency / Q000378:metabolism
D001391:Azo Compounds; D002839:Chromans; D009570:Nitriles; C055792:2,2'-azobis(2,4-dimethylvaleronitrile); D014810:Vitamin E; D009249:NADP; C029141:2,2,5,7,8-pentamethyl-1-hydroxychroman; D003676:Deferoxamine