title: Antioxidant, anticonvulsive and neuroprotective effects of dapsone and phenobarbital against kainic acid-induced damage in rats.
abstract: Excitotoxicity due to glutamate receptors (GluRs) overactivation is a leading mechanism of oxidative damage and neuronal death in various diseases. We have shown that dapsone (DDS) was able to reduce both neurotoxicity and seizures associated to the administration of kainic acid (KA), an agonist acting on AMPA/KA receptors (GluK1-GluK5). Recently, it has been shown that phenobarbital (PB) is also able to reduce epileptic activity evoked by that receptor. In the present study, we tested the antioxidative, anticonvulsive and neuroprotective effects of DDS and PB administered alone or in combination upon KA toxicity to rats. Results showed that KA increased lipid peroxidation and diminished reduced glutathione (GSH), 24 h after KA administration and both drugs in combination or individually inhibited these events. Likewise, KA promotes mortality and this event was antagonized by effect of both treatments. Additionally, the behavioral evaluation showed that DDS and PB administered alone or in combination decreased the number of limbic seizures and reduced the percentage of animals showing tonic-clonic seizures versus the control group, which was administered only with KA. Finally, our study demonstrated that all of the treatments prevented the neuronal death of the pyramidal cell layer of hippocampal CA-3. In conclusion, the treatment with DDS and PB administrated alone or in combination exerted antioxidant, anticonvulsive and neuroprotective effects against the neurotoxicity induced by KA in rats, but their effects were not additive. Thus, it may be good options of treatment in diseases such as epilepsy and status epilepicus, administered separately.
authors.affiliation: Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, S.S.A., Ave. Insurgentes Sur, No. 3877, C.P. 14269, Mexico, DF, Mexico.
authors.forename: Araceli
authors.initials: A
authors.lastname: Diaz-Ruiz
authors.forename: Marisela
authors.initials: M
authors.lastname: Mendez-Armenta
authors.forename: Sonia
authors.initials: S
authors.lastname: Galván-Arzate
authors.forename: Joaquín
authors.initials: J
authors.lastname: Manjarrez
authors.forename: Concepción
authors.initials: C
authors.lastname: Nava-Ruiz
authors.forename: Iván
authors.initials: I
authors.lastname: Santander
authors.forename: Gustavo
authors.initials: G
authors.lastname: Balderas
authors.forename: Camilo
authors.initials: C
authors.lastname: Ríos
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D003622:Dapsone / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000927:Anticonvulsants; D000975:Antioxidants; D018696:Neuroprotective Agents; D003622:Dapsone; D005978:Glutathione; D007608:Kainic Acid; D010634:Phenobarbital