Citotoxicity of Fipronil on Hepatocytes Isolated from Rat and Effects of Its Biotransformation
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Data
2015-11-01
Autores
Guelfi, Marieli [UNESP]
Maioli, Marcos Antonio [UNESP]
Tavares, Marco Aurelio [UNESP]
Mingatto, Fabio Erminio [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Inst Tecnologia Parana
Resumo
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.
Descrição
Palavras-chave
fipronil, hepatotoxicity, bioenergetics, biotransformation, calcium homeostasis
Como citar
Brazilian Archives Of Biology And Technology. Curitiba-parana: Inst Tecnologia Parana, v. 58, n. 6, p. 843-853, 2015.