Protective effect of disubstituted diaryl diselenides on cerebral oxidative damage caused by sodium nitroprusside

Abstract

Disubstituted diaryl diselenides, a class of organoselenium compounds, were investigated for antioxidant activity in rat brain homogenates. Diphenyl diselenide (PhSe)2, m-trifluoromethyl-diphenyl diselenide (m-CF3–C6H4Se)2, p-chloro-diphenyl diselenide (p-Cl–C6H4Se)2 and p-methoxyl-diphenyl diselenide (p-CH3O–C6H4Se)2 were tested against lipid peroxidation (LP) induced by sodium nitroprusside (SNP) or malonate and oxidatively modified proteins (OP) induced by SNP in vitro. Disubstituted diaryl diselenides protected against LP and OP. Disubstituted diaryl diselenides were investigated against oxidative damage caused by SNP in mouse brain. Mice were pre-treated with disubstituted diaryl diselenides (25mg/kg, oral route, p.o.) and subsequently received SNP (0.35μM/site i.c.v.). The levels of LP and OP, and activities of catalase, δ-aminolevulinate dehydratase (δ-ALA-D) and Na+, K+-ATPase were evaluated in vivo. All disubstituted diaryl diselenides protected against the increase of LP and OP induced by SNP, while only (PhSe)2 and (m-CF3–C6H4Se)2 were able to protect against δ-ALA-D and Na+, K+-ATPase inhibition induced by SNP. In conclusion, (p-Cl–C6H4Se)2 and (m-CF3–C6H4Se)2 were most efficient against lipid and protein oxidation in rat brain homogenates in vitro. All disubstituted diaryl diselenides protected against oxidative damage caused by the administration of SNP in mice in vivo.