The mechanism of NADPH-dependent lipid peroxidation. The propagation of lipid peroxidation.

Svingen, Bruce A.; Buege, John A.; O'Neal, F O; Aust, Steven D.

doi:10.1016/s0021-9258(18)50498-1

Cited by 369 publications

(15 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lipid hydroperoxides generated upon ADP−iron-dependent initiation of peroxidative processes are known to react with cytochrome P450. This process accompanies destruction of the hemoprotein and liberates lipid alkoxyl radicals which reinitiate hydrogen abstraction from polyunsaturated fatty acid, thus propagating lipid peroxidation ( , ). In this respect, Table shows that (i) ADP−Fe(II)-dependent microsomal lipid peroxidation predictably caused the destruction of cytochrome P450 and (ii) the addition of IDBH 2 prevented cytochrome P450 destruction, although less effectively as compared with the concomitant inhibition of TBARS formation (75% vs 98%).…”

Section: Resultsmentioning

confidence: 99%

“…The latter observation suggested that IDBH 2 uncoupled the destruction of cytochrome P450 from the propagation of lipid peroxidation. Inasmuch as propaga- tion accounts for g90% of TBARS formation (42), we could therefore calculate the ratio of TBARS to cytochrome P450 destruction as a tentative index of lipid radical reactions mediated by the hemoprotein. As also shown in Table 2, IDBH 2 decreased this ratio by greater than 95% in comparison with control incubations, confirming that IDBH 2 could interfere with the propagation of lipid peroxidation.…”

Section: Interaction Of Idebenone With Dpph and Abtsmentioning

confidence: 99%

See 1 more Smart Citation

Antioxidant Properties of 2,3-Dimethoxy-5-methyl- 6-(10-hydroxydecyl)-1,4-benzoquinone (Idebenone)

Mordente

Martorana

Minotti

et al. 1998

Chem. Res. Toxicol.

104

View full text Add to dashboard Cite

Idebenone [2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone] is a synthetic analogue of coenzyme Q that is currently employed in the treatment of vascular and degenerative diseases of the central nervous system. There is some evidence to suggest that idebenone might function as an antioxidant; however, it has not been demonstrated whether this function pertains to the quinone or hydroquinone form of idebenone. Here we demonstrate that idebenone can scavenge a variety of free radical species, including organic radicals such as 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and diphenylpicrylhydrazyl, peroxyl and tyrosyl radicals, and peroxynitrite. Idebenone can also redox couple with hypervalent species of Mb or Hb, thus preventing lipid peroxidation promoted by these species. Likewise, idebenone inhibits microsomal lipid peroxidation induced by ADP-iron complexes or organic hydroperoxides. In so doing, idebenone prevents the destruction of cytochrome P450, which otherwise would accompany lipid peroxidation. Irrespective of the experimental system under investigation, idebenone functions by virtue of the electron-donating properties of the hydroquinone form. Redox coupling of this hydroquinone with free radicals generates the quinone compound, which per se lacks antioxidant activity. In many experiments, the antioxidant effects of idebenone become appreciable at approximately 2 microM, which is well in the range of plasma levels attainable in patients given oral doses of this drug. Moreover, comparative experiments have shown that the antioxidant efficiency of idebenone varies from no less than 50% to slightly more than 100% of that of vitamin E or Trolox. We would therefore propose that the neuroprotective effects of idebenone can be attributed, at least in part, to its ability to function as an antioxidant, involving redox cycling between hydroquinone and quinone.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Interaction Of Idebenone With Dpph and Abtsmentioning

confidence: 99%

Antioxidant Properties of 2,3-Dimethoxy-5-methyl- 6-(10-hydroxydecyl)-1,4-benzoquinone (Idebenone)

Mordente

Martorana

Minotti

et al. 1998

Chem. Res. Toxicol.

104

View full text Add to dashboard Cite

show abstract

“…Membranal phospholipids are particularly susceptible to oxidation not only because of their high polyunsaturated fatty acid content but also because of their association in the cell membrane with enzymic and nonenzymic systems capable of generating prooxidative free-radical species (Svingen et al, 1979; Sevanian and Hochstein, 1985; Hsieh and Kinsella, 1989;Halliwell and Gutteridge, 1990). To effectively control lipid oxidation in muscle foods at the initiation stage, procedures that stabilize membranal lipids are of interest.…”

Section: Introductionmentioning

confidence: 99%

Influence of diet on lipid oxidation and membrane structure in porcine muscle microsomes

Monahan

Gray

Asghar

et al. 1994

J. Agric. Food Chem.

View full text Add to dashboard Cite

“…Fatty acid hydroperoxides arise in nature by lipid peroxidation (Tappel, 1973;Bus & Gibson, 1979;Svingen et al, 1979) or during prostaglandin and leukotriene biosynthesis (Hamberg & Samuelsson, 1974;Samuelsson et al, 1978;Gardner, 1980;Samuelsson, 1983). Alkyl hydroperoxides such as peroxy-Y-base, a component of tRNA1"116 (Feinberg et al, 1974), and 4a-hydroperoxyflavin, an intermediate in flavin oxidase (Kemal & Bruice, 1976), have also been isolated in mammalian tissue.…”

mentioning

confidence: 99%

Reaction of hematin with allylic fatty acid hydroperoxides: identification of products and implications for pathways of hydroperoxide-dependent epoxidation of 7,8-dihydroxy-7,8-dihydrobenzol[a]pyrene

Labeque¹,

Marnett²

1988

Biochemistry

View full text Add to dashboard Cite

Reaction of 10-hydroperoxyoctadec-8-enoic acid (10-OOH-18:1) (50 microM) with hematin (0.5 microM) in sodium phosphate buffer containing Tween 20 (200 microM) generates 10-oxooctadec-8-enoic acid, 10-oxodec-8-enoic acid (10-oxo-10:1), and 10-hydroxyoctadec-8-enoic acid in relative yields of 79, 4, and 17%, respectively. The product profile and relative distribution are unaffected by 1 mM butylated hydroxyanisole. Approximately 5% of the hydroperoxide isomerizes from the 10- to the 8-position. 10-Oxo-10:1 most likely arises via beta-scission of an intermediate alkoxyl radical to the aldehyde and the n-octyl radical. To test this, 10-hydroperoxyoctadeca-8,12-dienoic acid was reacted with hematin under identical conditions. 10-Oxooctadeca-8,12-dienoic acid, 10-oxodec-8-enoic acid, and 10-hydroxyoctadeca-8,12-dienoic acid are formed in relative yields of 50, 45, and 5%, respectively. The product ratios are constant with time and hydroperoxide to catalyst ratio and unaffected by inclusion of phenolic antioxidants. The higher yield of 10-oxo-10:1 from 10-OOH-18:2 compared to 10-OOH-18:1 is due to the higher rate of beta-scission of the intermediate alkoxyl radical from the former to the resonance-stabilized octenyl radical. Two products of reaction of the 2-octenyl radical with O2, octenal and octenol, were detected in 10% yield relative to 10-oxo-10:1. Inclusion of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) led to epoxidation by both 10-OOH-18:1 and 10-OOH-18:2. Studies with isotopically labeled hydroperoxide or O2 indicated approximately 65% of the epoxide oxygen was derived from O2 and 35% from hydroperoxide oxygen, consistent with the involvement of peroxyl free radicals as the oxidizing agents. The available evidence indicates that hematin reduces the fatty acid hydroperoxides homolytically to alkoxyl radicals that are oxidized to ketones, reduced to alcohols, or undergo beta-scission to aldehydes. Carbon radicals generated during these reactions couple to O2, generating peroxyl free radicals that epoxidize BP-7,8-diol. The smaller percentage of epoxidation that results from hydroperoxide oxygen may arise from oxidation of the hydroperoxide group to peroxyl radicals or from heterolytic cleavage of the hydroperoxide to alcohol and an iron-oxo complex.

show abstract

The mechanism of NADPH-dependent lipid peroxidation. The propagation of lipid peroxidation.

Cited by 369 publications

References 48 publications

Antioxidant Properties of 2,3-Dimethoxy-5-methyl- 6-(10-hydroxydecyl)-1,4-benzoquinone (Idebenone)

Antioxidant Properties of 2,3-Dimethoxy-5-methyl- 6-(10-hydroxydecyl)-1,4-benzoquinone (Idebenone)

Influence of diet on lipid oxidation and membrane structure in porcine muscle microsomes

Reaction of hematin with allylic fatty acid hydroperoxides: identification of products and implications for pathways of hydroperoxide-dependent epoxidation of 7,8-dihydroxy-7,8-dihydrobenzol[a]pyrene

Contact Info

Product

Resources

About