Wilhelm_2010_Life.Sci_87_620

AIM: This study investigated the in vitro antioxidant activity of (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD), the anticonvulsant effect of BPD on seizures induced by pilocarpine (PC), pentylenetetrazole (PTZ) and 4-aminopyridine (4-AMP) and the mechanism involved. METHODS: BPD antioxidant activity in vitro was investigated using sodium nitroprusside (SNP) and malonate-induced thiobarbituric acid reactive species (TBARS) and sodium azide-induced reactive species (RS) production. Thiol peroxidase and oxidase as well as delta-aminolevulinate dehydratase (delta-ALA-D) activities were examined. Mice were pretreated via oral route (p.o.) with BPD (1-100 mg/kg) before intraperitoneal (i.p.) administration of PC (400 mg/kg), PTZ (80 mg/kg) or 4-AMP (12 mg/kg). To investigate the antioxidant effect of BPD on oxidative stress induced by PC, the activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase (CAT) as well as the levels of RS and TBARS were determined in brains of mice. delta-ALA-D, acetylcholinesterase (AChE) and Na(+), K(+) ATPase activities were verified. KEY FINDINGS: BPD (5 muM) reduced RS production and lipid peroxidation induced by SNP and malonate. BPD (1-50 muM) did not show thiol peroxidase and oxidase activities and did not alter delta-ALA-D activity. BPD (5 mg/kg) increased the latency to the seizure onset on PTZ and 4-AMP models. BPD (100 mg/kg) abolished seizures and death induced by PC in mice. BPD protected against the increase in RS and TBARS levels. The activity of Na(+), K(+) ATPase and AChE inhibited by PC remained unaltered in the BPD group. SIGNIFICANCE: BPD showed anticonvulsant and antioxidant effects on seizures induced by PC in mice.