The most direct mechanism of liver toxicity, at the cellular and molecular level, is the specific interaction of the toxicant with a critical cellular component (mitochondria, for example) and subsequent modulation of its function (Meyer and Kulkarni, 2001). ABA poisoning can impair

the function of hepatocytes. Research conducted by Hsu et al. (2001) showed elevated levels of the enzyme aspartate aminotransferase (AST) in the MK 2206 blood serum of rats after exposure to ABA by gavage at doses between 1 and 20 mg/kg body weight. The maximum activity was obtained with a dose of 20 mg/kg of body weight 1 h after ingestion. Eissa and Zidan (2010), using a commercial product, also observed signs of abamectin liver toxicity, with increased activity of the enzyme AST in rats treated with doses equivalent to 1/10 or 1/100 of the LD50 (18 mg/kg) in the diet of animals over 30 consecutive days. In addition, El-Shenawy (2010) undertook a comparative study of the in vitro toxic action of some insecticides, including ABA at concentrations of 10 and 100 μM, on isolated rat hepatocytes. There was a significant increase in alanine aminotransferase NVP-BGJ398 manufacturer (ALT) and aspartate

aminotransferase (AST) activity when hepatocytes were incubated for 30 min with either concentration of ABA. This activity persisted after 120 min, the longest time point for which data was collected.

Mitochondria carry out a variety of biochemical processes, but their main function is to produce a majority (>90%) of cellular ATP. The proton motive force, whose major impetus is the membrane potential (Δψ) generated by electron transport along the respiratory chain in the inner mitochondrial membrane, drives ATP synthesis via oxidative phosphorylation (Mitchell, 1961). Experimental evidence from our research group indicates that mitochondria Ureohydrolase represent a primary target critical for the action of drugs and toxins (Mingatto et al., 2000, Mingatto et al., 2007 and Garcia et al., 2010). Here, we addressed the actions of ABA on mitochondrial bioenergetics by assessing its effect on respiration, membrane potential, ATP levels, activity of mitochondrial respiratory chain enzymes, ATPase and ANT in isolated rat liver mitochondria. Abamectin, containing 92% avermectin B1a and 8% avermectin B1b, was kindly supplied by the company Ourofino Agribusiness (Cravinhos, São Paulo, Brazil). All other reagents were of the highest commercially available grade. Dimethyl sulfoxide (DMSO) used to dissolve abamectin had no effect on the assays. The volume of DMSO added never exceeded 0.1% of the total volume of medium. All stock solutions were prepared using glass-distilled deionized water. Male Wistar rats weighing approximately 200 g were used in this study.