Diphenyl diselenide confers neuroprotection against hydrogen peroxide toxicity in hippocampal slices

Abstract

The present study aimed at investigating the potential in vitro protective effect of the organochalcogenide diphenyl diselenide – (PhSe) 2 – against hydrogen peroxide (H 2O 2)-induced toxicity in rat hippocampal slices. Hippocampal slices were treated for 1 h with H 2O 2 (2 mM) in the presence or absence of (PhSe) 2 (0.1–10 μM). H 2O 2 treatment significantly decreased cell viability (measured by MTT test) and the co-incubation with (PhSe) 2 (10 μM) significantly blunted such phenomenon. The non permeable thiol compounds dithiothreitol (DTT) (100 μM) or reduced glutathione (GSH) (100 μM), which did not display protective effects against H 2O 2-induced loss of cell viability per se, significantly improved the protective effects elicited by (PhSe) 2. Conversely, the permeable form of GSH (GSH monoethyl ester) was unable to alter the neuroprotection mediated by (PhSe) 2. The treatment of rat hippocampal slices with H 2O 2 also increased the lipid peroxidation and decreased the intracellular GSH levels. Moreover, (PhSe) 2 (from 0.1 μM) significantly decreased H 2O 2-induced lipid peroxidation. Interestingly, H 2O 2 decreased GSH levels and this phenomenon was partially prevented by (PhSe) 2. The potential effects of H 2O 2 on MAPKs phosphorylation (ERK1/2, p38 MAPK and JNK1/2) were also evaluated. Even though H 2O 2 (2 mM) did not alter p38 MAPK and JNK1/2 phosphorylation in hippocampal slices, it stimulated ERK1/2 phosphorylation and the co-incubation with (PhSe) 2 (10 μM) blocked this effect. Taken together, the present results indicate that (PhSe) 2 exerts protective effects against H 2O 2-induced oxidative damage in hippocampal slices and avoided the increase in ERK1/2 phosphorylation promoted by H 2O 2. The neuroprotective effect of compound seems to be related to its thiol-peroxidase-like activity and appears to occur at the extracellular milieu because a permeable form of GSH was unable to improve the protective effect of the compound as did the impermeable GSH.