Anticonvulsant and antioxidant effects of 3-alkynyl selenophene in 21-day-old rats on pilocarpine model of seizures.
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.
Wilhelm
Ethel A
EA
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Jesse
Cristiano R
CR
Bortolatto
Cristiani F
CF
Nogueira
Cristina W
CW
Savegnago
Lucielli
L
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007608:Kainic Acid; D008297:Male; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D010433:Pentylenetetrazole; D010862:Pilocarpine; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome
D000927:Anticonvulsants; D000975:Antioxidants; D018691:Excitatory Amino Acid Antagonists; D016566:Organoselenium Compounds; D011810:Quinoxalines; D010862:Pilocarpine; C056723:FG 9041; D016291:Dizocilpine Maleate; D003975:Diazepam; D007608:Kainic Acid; D010433:Pentylenetetrazole