Enhancement of Iron-Catalyzed Free Radical Formation by Acidosis in Brain Homogenates: Difference in Effect by Lactic Acid and CO 2

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% CO₂ gas 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 CO₂ tension. It is suggested that this effect of lactic acid is mediated by increased dissociation of catalytic iron from proteins of the transferrin type.