Antioxidant activity of dihydrolipoate against microsomal lipid peroxidation and its dependence on alpha-tocopherol.
The antioxidant effect of dihydrolipoate and lipoate was examined in microsomal fractions obtained from normal and alpha-tocopherol-deficient animals after initiation of lipid peroxidation with an NADPH/iron/ADP system. Dihydrolipoate prolonged the lag phase before the onset of low-level chemiluminescence and before the rapid accumulation of thiobarbituric acid-reactive substances in normal but not in vitamin E-deficient microsomes. Lipoate did not show such an antioxidant effect. It is concluded that the dihydrolipoate-mediated protection against lipid peroxidation by prolonging the lag phase is dependent on alpha-tocopherol. Likewise, dihydrolipoate prolonged the lag phase before the onset of the rapid loss of vitamin E during lipid peroxidation. Dihydrolipoate, like other biological thiols such as GSH, also affects the peroxidative process after the lag period. The effects included a smaller slope of the chemiluminescence increase, a lower maximal level of chemiluminescence, a slower loss of alpha-tocopherol and a slower accumulation, but unchanged maximal levels, of thiobarbituric acid-reactive substances. The biological significance may be most prominent in the mitochondrial matrix space, where lipoamide-containing ketoacid dehydrogenases are located. A potential pharmacological use of this biological dithiol in conditions associated with oxidative stress could be based on the antioxidant activity of dihydrolipoate.
Scholich
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Institut für Physiologische Chemie I, Universität Düsseldorf, F.R.G.
Murphy
M E
ME
Sies
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H
D000818:Animals; D008054:Lipid Peroxides / Q000378:metabolism*; D008163:Luminescent Measurements; D008861:Microsomes / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013858:Thiobarbiturates; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology*
D008054:Lipid Peroxides; D013858:Thiobarbiturates; D014810:Vitamin E; D008063:Thioctic Acid; C015144:dihydrolipoic acid; C029684:thiobarbituric acid