Effect of acidosis and anoxia on iron delocalization from brain homogenates.

Cortical homogenates were prepared from rat brain in Krebs-Ringer phosphate media adjusted to pH 7, 6 or 5 and incubated for 1 hr under aerotic or anaerobic conditions in the presence of dipyridyl, an iron chelator. Low molecular weight species (LMWS) iron was measured spectrophotometrically after passing of the homogenates through a 10,000-Mr ultrafiltration membrane. Following aerobic incubation, LMWS iron reached 1.24 micrograms/g tissue at pH 7, and increased 1.7-fold at pH 6 and 3.1-fold at pH 5. Anoxia enhanced significantly the amount of ultrafiltrable iron at the three pH values, the LMWS iron level being increased by 190% at pH 7, by 113% at pH 6, and by 77% at pH 5. Addition of the ultrafiltrates to brain membranes caused significant rises in the production of lipid peroxides assessed by the thiobarbituric acid test, indicating that LMWS iron was in a form capable for catalysing oxygen-derived free radical-mediated lipid peroxidation. It was concluded that decompartmentalization of intracellular iron may be an important factor in the initiation of peroxidative damage to ischemic cells.