Fumonisin B1 facilitates seizures induced by pentylenetetrazol in mice.
Fumonisin B1 (FB1) is a Fusarium spp. mycotoxin which constitutes a major public health issue because of its worldwide distribution and diversity of toxic effects.While the liver and kidney are considered the major target organs of FB1 toxicity in several species, evidence indicates that FB1 may be toxic to the brain. To further investigate the effects of FB1 on the central nervous system the present study aimed to test the hypothesis that acute FB1 exposure causes brain hyperexcitability and the potential underlying mechanisms. For these purposes, adult male C57BL/6 mice were injected with FB1 (8 mg/kg, i.p.) or its vehicle and 30 min thereafter received with a low dose of the classical convulsant pentylenetetrazol (PTZ, 30 mg/kg, i.p.) or its vehicle. After behavioral evaluation the cerebral cortex and the hippocampus were collected for analysis of Na(+),K(+)-ATPase activity, mitochondrial membrane potential (ΔΨm) and mitochondrial complex I and II activities. We found that FB1 reduced the latency for PTZ-induced myoclonic jerks and increased the number of these events. After exposure to FB1 total and α1 Na(+),K(+)-ATPase activities increased in cerebral cortex, whereas the same enzyme activities decreased in the hippocampus. Although no changes in mitochondrial complex I and II activities were found, acute exposure to FB1 increased ΔΨm in the cerebral cortex. Altogether, present results indicate that FB1 causes brain hyperexcitability in vivo, and that mitochondrial dysfunction may represent a potential underlying mechanism.
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil.
Alice Bertotto
AB
Poersch
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil.
Francielle
F
Trombetta
Programa de Pós Graduação em Ciência e Tecnologia dos Alimentos, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil.
Naiéli Schiefelbein
NS
Souto
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil.
Camilla
C
de Oliveira Lima
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil.
Ana Cláudia Monteiro
AC
Braga
Programa de Pós Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Campus UFSM, Santa Maria, RS 97105-900, Brazil.
Fernando
F
Dobrachinski
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil.
Leandro Rodrigo
LR
Ribeiro
Programa de Pós Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Campus UFSM, Santa Maria, RS 97105-900, Brazil.
Félix Alexandre Antunes
FA
Soares
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil.
Michele Rechia
MR
Fighera
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil; Programa de Pós Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Campus UFSM, Santa Maria, RS 97105-900, Brazil.
Luiz Fernando Freire
LF
Royes
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil; Programa de Pós Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Campus UFSM, Santa Maria, RS 97105-900, Brazil.
Mauro Schneider
MS
Oliveira
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil; Programa de Pós Graduação em Ciência e Tecnologia dos Alimentos, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil. Electronic address: furian.anaflavia@gmail.com.
Ana Flávia
AF
Furian
D000704:Analysis of Variance; D000818:Animals; D003292:Convulsants / Q000633:toxicity*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000633:toxicity*; D037341:Fumonisins / Q000633:toxicity*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009245:NADH Dehydrogenase / Q000378:metabolism; D010433:Pentylenetetrazole / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D003292:Convulsants; D004791:Enzyme Inhibitors; D037341:Fumonisins; C056933:fumonisin B1; D009245:NADH Dehydrogenase; D000254:Sodium-Potassium-Exchanging ATPase; D010433:Pentylenetetrazole
Fumonisin B1; Mitochondrial membrane potential; Neurotoxicity; Seizure