Influence of acidosis on lipid peroxidation in brain tissues in vitro.

To study the influence of acidosis on free radical formation and lipid peroxidation in brain tissues, homogenates fortified with ferrous ions and, in some experiments, with ascorbic acid were equilibrated with 5-15% O2 at pH values of 7.0, 6.5, 6.0, and 5.0, with subsequent measurements of thiobarbituric acid-reactive (TBAR) material, as well as of water- and lipid-soluble antioxidants (glutathione, ascorbate, and alpha-tocopherol) and phospholipid-bound fatty acids (FAs). Moderate to marked acidosis (pH 6.5-6.0) was found to grossly exaggerate the formation of TBAR material and the decrease in alpha-tocopherol content and to enhance degradation of phospholipid-bound, polyenoic FAs. These effects were reversed at pH 5.0, suggesting a pH optimum at pH 6.0-6.5. It is concluded that acidosis of a degree encountered in ischemic brain tissues has the potential of triggering increased free radical formation. This effect may involve increased formation of the protonated form of superoxide radicals, which is strongly prooxidant and lipid soluble, and/or the decompartmentalization of iron bound to cellular macromolecules like ferritin.