Enhancement of Iron-Catalyzed Free Radical Formation by Acidosis in Brain Homogenates: Difference in Effect by Lactic Acid and CO2

Abstract

The influence of lactic acidosis and of extreme hypercapnia on free radical generation and lipid peroxidation in brain tissues was studied. Cortical homogenates were prepared from the rat brain in a bicarbonate buffer and incubated for 60 min. Lipid peroxidation was evaluated by measurements of thiobarbituric acid reactive (TBAR) material and α-tocopherol analysis. The pH during incubations were decreased to 6.10–6.20 by either lactic acid administration or equilibration with 60% CO2gas in paired experiments. In homogenates treated with lactic acid there was a 20-fold increase in TBAR material and the α-tocopherol concentration decreased to ∼60% of control. There was only a 10-fold increase in TBAR material and no change in α-tocopherol concentration if acidosis was induced by CO2. These differences between lactic acidosis and hypercapnic acidosis were statistically highly significant. The results indicate that lactic acidosis has a more pronounced effect in augmenting free radical generation in brain tissues than acidosis due to an increase in CO2tension. It is suggested that this effect of lactic acid is mediated by increased dissociation of catalytic iron from proteins of the transferrin type.