Diphenyl diselenide and diphenyl ditelluride increase the latency for 4-aminopyridine-induced chemical seizure and prevent death in mice.
In this work was investigated the effect of pre-treatment with (PhSe)(2) and (PhTe)(2) on chemical seizure and 4-aminopyridine-induced lethality in mice. Additionally, lipid peroxidation levels of whole brain after treatment with 4-aminopyridine and effect of pre-treatment with (PhSe)(2) and (PhTe)(2) on these levels were investigated. Mice were pre-treated with (PhSe)(2) or (PhTe)(2) (50, 100, or 150 micromol/kg) 30 min before 4-aminopyridine (12 mg/kg) administration. The treatment with 4-aminopyridine caused a significant incidence of seizures (clonic, tonic) and death. Pre-treatment with (PhSe)(2) and (PhTe)(2) significantly increased the latency for clonic and tonic seizures, and prevented 4-aminopyridine-induced death. Significantly, the pre-treatment with (PhSe)(2) or (PhTe)(2) increased the latency for clonic seizures in a dose-dependent manner. Additionally, a significant increase was observed in the brain lipid peroxidation level after treatment with 4-aminopyridine, which was significantly inhibited by pre-treatment with 150 micromol/kg (PhSe)(2) or (PhTe)(2). These results demonstrate that (PhSe)(2) and (PhTe)(2) counteract the harmful effects of 4-aminopyridine. It is possible that this effect results from modulation of the redox state of N-methyl-d-aspartate receptors and/or of Ca(2+) channel activity with subsequent alteration in neurotransmitter release. Importantly, this study provides evidence for anticonvulsant and antioxidant properties of (PhSe)(2) and (PhTe)(2), which indicates a neuroprotective activity of these compounds.
Brito
Verônica B
VB
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Brasil. brito.veronica@gmail.com
Rocha
João Batista T
JB
Folmer
Vanderlei
V
Erthal
Fernando
F
D015761:4-Aminopyridine / Q000633:toxicity*; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009942:Organometallic Compounds / Q000494:pharmacology*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*
D001555:Benzene Derivatives; D009942:Organometallic Compounds; D016566:Organoselenium Compounds; C434247:diphenylditelluride; C061132:diphenyldiselenide; D015761:4-Aminopyridine