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


RESULTS
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.


CONCLUSIONS
BPD showed anticonvulsant and antioxidant effects on seizures induced by PC in mice.
Wilhelm
Ethel A
EA
Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Jesse
Cristiano R
CR
Roman
Silvane Souza
SS
Bortolatto
Cristiani F
CF
Nogueira
Cristina W
CW
D015761:4-Aminopyridine; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008314:Malonates; D051379:Mice; D009599:Nitroprusside; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010433:Pentylenetetrazole; D010862:Pilocarpine; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
C553968:2-benzylidene-4-phenyl-1,3-diselenole; D000927:Anticonvulsants; D000975:Antioxidants; D008314:Malonates; D016566:Organoselenium Compounds; D017392:Thiobarbituric Acid Reactive Substances; D010862:Pilocarpine; D009599:Nitroprusside; C030290:malonic acid; D015761:4-Aminopyridine; D010433:Pentylenetetrazole