Citotoxicity of Fipronil on Hepatocytes Isolated from Rat and Effects of Its Biotransformation

Autor(es)

Guelfi, Marieli ^[1] ; Maioli, Marcos Antonio ^[2] ; Tavares, Marco Aurelio ^[1] ; Mingatto, Fabio Erminio ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista, Dept Zootecnia, Dracena, SP - Brazil

^[2] Univ Estadual Paulista, Prod & Saude Anim, Aracatuba, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Archives of Biology and Technology; v. 58, n. 6, p. 843-853, NOV-DEC 2015.
• Citações Web of Science: 4

Resumo

ABSTRACT The aim of this study was to characterize the mechanism of toxicity of fipronil on hepatocytes isolated from the rat and the effect of its biotransformation on the toxicological potential. The toxicity of fipronil was assessed by monitoring the oxygen consumption and mitochondrial membrane potential, intracellular ATP concentration, Ca2+ homeostasis and cell viability. The cell viability was evaluated by trypan blue exclusion in hepatocytes that were isolated from the normal rats and by the release of the enzymes alanine transaminase and aspartate transaminase in hepatocytes that were isolated from the normal rats or proadifen-pretreated rats. Fipronil reduced mitochondrial respiration in the cells that were energized with glutamate plus malate in a dose-dependent manner and dissipated the mitochondrial membrane potential that was accompanied by a reduction in ATP concentration and a disruption of intracellular Ca2+ homeostasis. The cell viability was affected by fipronil with higher potency in hepatocytes that were isolated from the normal rats, which indicated that the metabolism of this insecticide increased its toxicological potential. The results of this study indicated that the toxicity of fipronil to the hepatocytes was related to the inhibition of mitochondrial activity, which led to decreased ATP synthesis and a consequent alteration in intracellular Ca2+ homeostasis and ultimately resulted in cell death. (AU)

• Processo FAPESP: 12/24872-4 - Mecanismos de toxicidade do fipronil em hepatócitos isolados de ratos
• Beneficiário: Marieli Guelfi
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 12/15135-6 - Mecanismos de toxicidade do fipronil em mitocôndrias e hepatócitos isolados de ratos
• Beneficiário: Fábio Erminio Mingatto
• Modalidade de apoio: Auxílio à Pesquisa - Regular