Anticonvulsant and antioxidant effects of 3-alkynyl selenophene in 21-day-old rats on pilocarpine model of seizures

Brain Res Bull. 2009 Jun 30;79(5):281-7. doi: 10.1016/j.brainresbull.2009.03.006. Epub 2009 Apr 1.

Abstract

This study investigated the anticonvulsant effect of 3-alkynyl selenophene (3-ASP) on pilocarpine (PC)-, pentylenetetrazole (PTZ)- and kainic acid (KA)-induced seizures and mortality in 21-day-old rats. Rats were pretreated by oral route (p.o.) with 3-ASP (10, 25 and 50mg/kg) before intraperitoneal (i.p.) administration of PC (400mg/kg), PTZ (80 mg/kg) or KA (45 mg/kg). 3-ASP increased the latency to the seizure onset on PTZ and KA models. At the dose of 50mg/kg, 3-ASP avoided the death caused by PTZ and KA. 3-ASP (50mg/kg) abolished seizures and death induced by PC in rats. To investigate the antioxidant effect of 3-ASP on rats exposed to PC, the activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), acetylcholinesterase (AChE), Na(+)K(+)ATPase, superoxide dismutase (SOD) and catalase (CAT) as well as the levels of reactive species (RS) and ascorbic acid (AA) were determined in brains of rats. 3-ASP protected against the increase in RS levels and CAT activity induced by PC in brains of rats. The decrease in the levels of AA and inhibition of Na(+)K(+)ATPase, SOD and AChE activities caused by PC were protected by 3-ASP. Subeffective doses of 3-ASP plus diazepam, 5S,10R-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) or 6,7-dinitroquinoxaline-2,3-dione (DNQX) increased the latency to the seizure onset induced by PC, suggesting the involvement of ionotropic glutamatergic and GABAergic receptors in anticonvulsant action of 3-ASP. The anticonvulsant and antioxidant effects of 3-ASP in 21-day-old rats on PC model were demonstrated.

MeSH terms

  • Animals
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacology*
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Brain / drug effects
  • Brain / enzymology
  • Brain / metabolism
  • Diazepam / administration & dosage
  • Diazepam / pharmacology
  • Dizocilpine Maleate / administration & dosage
  • Dizocilpine Maleate / pharmacology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology
  • Kainic Acid
  • Male
  • Organoselenium Compounds / administration & dosage
  • Organoselenium Compounds / pharmacology*
  • Pentylenetetrazole
  • Pilocarpine
  • Quinoxalines / administration & dosage
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Wistar
  • Seizures / chemically induced
  • Seizures / drug therapy*
  • Seizures / mortality
  • Time Factors
  • Treatment Outcome

Substances

  • Anticonvulsants
  • Antioxidants
  • Excitatory Amino Acid Antagonists
  • Organoselenium Compounds
  • Quinoxalines
  • Pilocarpine
  • FG 9041
  • Dizocilpine Maleate
  • Diazepam
  • Kainic Acid
  • Pentylenetetrazole