Antioxidant activity of dihydrolipoate against microsomal lipid peroxidation and its dependence on alpha-tocopherol

Biochim Biophys Acta. 1989 Feb 20;1001(3):256-61. doi: 10.1016/0005-2760(89)90108-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Lipid Peroxides / metabolism*
  • Luminescent Measurements
  • Microsomes / drug effects*
  • Microsomes / metabolism
  • Rats
  • Thiobarbiturates
  • Thioctic Acid / analogs & derivatives*
  • Thioctic Acid / pharmacology
  • Time Factors
  • Vitamin E / pharmacology*


  • Lipid Peroxides
  • Thiobarbiturates
  • Vitamin E
  • Thioctic Acid
  • dihydrolipoic acid
  • thiobarbituric acid