Enhancement of iron-catalyzed lipid peroxidation by acidosis in brain homogenate: comparative effect of diphenyl diselenide and ebselen.

Iron is more soluble at lower pH values; therefore we hypothesized that decreasing the environmental pH would lead to increased iron-mediated lipid peroxidation. Diphenyl diselenide and ebselen are potential candidates as neuroprotective agent, particularly in situations involving overproduction of free radicals and involving cellular pH fall. The aim of the present study was (a) to investigate the relationship between lipid peroxidation and acidosis in brain homogenate and (b) to test the influence of pH on the antioxidant properties of diphenyl diselenide and ebselen. For the purpose rat brain homogenate was incubated at different pH ranging from physiological to acidic values and extent of lipid peroxidation was measured. Thiobarbituric acid-reactive species (TBARS) production significantly increased when homogenate was incubated in the pH (5.4-6.8) medium both in the absence and presence of Fe (II) as compared with physiological pH (7.4). These data indicate that lipid peroxidation processes, mediated by iron, are enhanced with decreasing extracellular pH. The iron mobilized may come from reserves where it is weakly bound. Diphenyl diselenide significantly protected TBARS production at all studied pH values while ebselen offered only a small statistically non-significant protection. However, calculated IC(50) for TBARS inhibition indicated that pH did not change anti-oxidant activities of the tested compounds. This study provides in-vitro evidence for acidosis induced oxidative stress in brain homogenate and anti-oxidant action of diphenyl diselenide.