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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The role of mitochondria and biotransformation in abamectin-induced cytotoxicity in isolated rat hepatocytes

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Author(s):
Maioli, Marcos A. [1] ; de Medeiros, Hyllana C. D. [1] ; Guelfi, Marieli [1] ; Trinca, Vitor [2] ; Pereira, Flavia T. V. [2] ; Mingatto, Fabio E. [1]
Total Authors: 6
Affiliation:
[1] Univ Estadual Paulista, UNESP, Lab Bioquim Metab & Toxicol LaBMeT, BR-17900000 Dracena, SP - Brazil
[2] Univ Estadual Paulista, UNESP, L MPE, BR-17900000 Dracena, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: TOXICOLOGY IN VITRO; v. 27, n. 2, p. 570-579, MAR 2013.
Web of Science Citations: 14
Abstract

Abamectin (ABA), which belongs to the family of avermectins, is used as a parasiticide; however, ABA poisoning can impair liver function. In a previous study using isolated rat liver mitochondria, we observed that ABA inhibited the activity of adenine nucleotide translocator and F0F1-ATPase. The aim of this study was to characterize the mechanism of ABA toxicity in isolated rat hepatocytes and to evaluate whether this effect is dependent on its metabolism. The toxicity of ABA was assessed by monitoring oxygen consumption and mitochondrial membrane potential, intracellular ATP concentration, cell viability, intracellular Ca2+ homeostasis, release of cytochrome c, caspase 3 activity and necrotic cell death. ABA reduces cellular respiration in cells energized with glutamate and malate or succinate. The hepatocytes that were previously incubated with proadifen, a cytochrome P450 inhibitor, are more sensitive to the compound as observed by a rapid decrease in the mitochondrial membrane potential accompanied by reductions in ATP concentration and cell viability and a disruption of intracellular Ca2+ homeostasis followed by necrosis. Our results indicate that ABA biotransformation reduces its toxicity, and its toxic action is related to the inhibition of mitochondrial activity, which leads to decreased synthesis of ATP followed by cell death. (C) 2012 Elsevier Ltd. All rights reserved. (AU)

FAPESP's process: 10/03791-0 - Effects of abamectin in isolated hepatocytes and perfused rat liver
Grantee:Marcos Antonio Maioli
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 10/08570-2 - Mechanisms of toxicity of abamectin in the rat liver
Grantee:Fábio Erminio Mingatto
Support Opportunities: Regular Research Grants