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

Abstract

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 δ-aminolevulinate dehydratase (δ-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. δ-ALA-D, acetylcholinesterase (AChE) and Na(+), K(+) ATPase activities were verified.

KEY FINDINGS:

BPD (5 μM) reduced RS production and lipid peroxidation induced by SNP and malonate. BPD (1-50 μM) did not show thiol peroxidase and oxidase activities and did not alter δ-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.

• Authors: Ethel A Wilhelm, Cristiano R Jesse, Silvane Souza Roman, Cristiani F Bortolatto, Cristina W Nogueira
• Journal: Life sciences (Life Sci) Vol. 87 Issue 19-22 Pg. 620-7 (Nov 20 2010) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 20888349 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• 2-benzylidene-4-phenyl-1,3-diselenole
• Anticonvulsants
• Antioxidants
• Malonates
• Organoselenium Compounds
• Thiobarbituric Acid Reactive Substances
• Pilocarpine
• Nitroprusside
• malonic acid
• 4-Aminopyridine
• Pentylenetetrazole

Topics

• 4-Aminopyridine
• Animals
• Anticonvulsants (administration & dosage, pharmacology)
• Antioxidants (administration & dosage, pharmacology)
• Brain (drug effects, metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Lipid Peroxidation (drug effects)
• Male
• Malonates
• Mice
• Nitroprusside
• Organoselenium Compounds (administration & dosage, pharmacology)
• Oxidative Stress (drug effects)
• Pentylenetetrazole
• Pilocarpine
• Seizures (drug therapy, physiopathology)
• Thiobarbituric Acid Reactive Substances (metabolism)