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.