ABA caused an increase in the concentration of the enzyme aspartate aminotransferase (AST) in serum in vivo and an increase in the concentration of AST and alanine aminotransferase (ALT) in vitro, which are used as indicators of damage to the hepatic parenchymal cells ( Klaassen and Eaton, 1991). We previously demonstrated that ABA inhibits the activity of FoF1-ATPase and adenine nucleotide translocator (ANT) when added at micromolar concentrations to isolated rat liver mitochondria, an effect associated with significantly reduced ATP synthesis ( Castanha Zanoli et al., 2012). FoF1-ATPase is an enzyme present in the inner

mitochondrial membrane that is responsible by ATP synthesis driven by the proton electrochemical gradient generated in the respiratory chain. The main components of the enzyme are Fo, an integral membrane protein that works as a proton channel, and F1, a hydrophilic moiety which Ribociclib contains the catalytic and

regulatory sites (Hatefi, 1993 and Pedersen, selleck compound 1996). ANT is other important component of the mitochondrial machinery of ATP synthesis because of its intrinsic adenine nucleotide translocase activity. ANT has been involved in both pathological (mitochondrial permeability transition formation/regulation and cell death) and physiological (adenine nucleotide exchange) mitochondrial events, making it a prime target for drug-induced toxicity (Oliveira and Wallace, 2006). The xenobiotic metabolism in the liver is accomplished by cytochrome P450 and its main C1GALT1 function is to increase the polarity of these substances, so excretion occurs more easily (Oga, 2008). However, this process is responsible for the toxic effects of numerous chemical compounds. The metabolites may cause adverse effects in the animal (Ioannides and Lewis, 2004, Mingatto et al., 2007 and Maioli et al., 2011) by changing a fundamental cellular component (mitochondria, for example) at the cellular and molecular level, thus modulating its function (Meyer and Kulkarni, 2001). Due to the important functions of the liver in animals and previous studies that indicated the occurrence of liver damage after the use of ABA, this study aims to characterize the mechanisms of

ABA toxicity on parameters related to bioenergetics and cell death and determine whether the toxicity induced by the compound is due to a possible activation following its metabolism in the liver. Abamectin, containing 92% avermectin B1a and 8% avermectin B1b, was kindly supplied by the company Ourofino Agribusiness (Cravinhos, SP, Brazil), proadifen was purchased from Sigma–Aldrich (St. Louis, MO, USA), and sodium pentobarbital was a gift from Cristália (Itapira, SP, Brazil). All other reagents were of the highest commercially available grade. Abamectin and proadifen were dissolved in anhydrous dimethyl sulfoxide (DMSO). All stock solutions were prepared using glass-distilled deionized water. Male Wistar rats aged 7–8 weeks and weighing approximately 200 g, were used in this study.