Anticonvulsant effect of (E)-2-benzylidene-4-phenyl-1,3-diselenole in a pilocarpine model in mice

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 mu M) reduced RS production and lipid peroxidation induced by SNP and malonate. BPD (150 mu M) 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. (C) 2010 Elsevier Inc. All rights reserved.