Diphenyl diselenide and diphenyl ditelluride increase the latency for 4-aminopyridine-induced chemical seizure and prevent death in mice.

Abstract

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.

• Authors: Verônica B Brito, João Batista T Rocha, Vanderlei Folmer, Fernando Erthal
• Journal: Acta biochimica Polonica (Acta Biochim Pol) Vol. 56 Issue 1 Pg. 125-34 ( 2009) ISSN: 0001-527X [Print] Poland
• PMID: 19238257 (Publication Type: Journal Article)

Chemical References

• Benzene Derivatives
• Organometallic Compounds
• Organoselenium Compounds
• diphenylditelluride
• diphenyldiselenide
• 4-Aminopyridine

Topics

• 4-Aminopyridine (toxicity)
• Animals
• Benzene Derivatives (pharmacology)
• Dose-Response Relationship, Drug
• Male
• Mice
• Organometallic Compounds (pharmacology)
• Organoselenium Compounds (pharmacology)
• Seizures (chemically induced, physiopathology, prevention & control)