EFFECTS OF IRON-INDUCED LIPID-PEROXIDATION AND OF ACIDOSIS ON CHOLINEUPTAKE BY SYNAPTOSOMES

The effects of iron-induced lipid peroxidation and of lactic acidosis on [H-3]choline uptake were investigated on crude synaptosomes prepare d from rat cerebral cortices. Fe2+-induced lipid peroxidation as evide nced from the production of thiobarbituric acid reactives substances ( TBARS) was correlated with a decrease in high-affinity choline uptake (HACU). Trolox C, a free radical scavenger, prevented both Fe2+-induce d TBARS production and decrease in HACU. Lactic acidosis (pH 6.0 for 3 0 or 60 min) increased the TBARS production with concomitant decrease in HACU (-48%, -78%, respectively). The acidosis dependent decrease wa s not reversible following pH 7.4 readjustment after 60 min acidosis. It was not prevented by trolox C, although trolox C inhibited the acid osis-induced production of TBARS. The results suggest that the contrib ution of acidosis to peroxidative damages is probably of less importan ce in comparison to other cytotoxic mechanisms.