However, the researchers did not observe a decrease in the mitochondrial membrane potential as was observed in this study. A possible explanation for the dissipation in the membrane potential caused by ABA in isolated hepatocytes may be related to a loss of intracellular Ca2+ homeostasis (Skulachev, 1999). When hepatocytes were exposed to 25 μM ABA, a loss of intracellular ion homeostasis occurred. As the Ca2+ concentration increased in the cell cytoplasm, the mitochondria selleck chemical captured the surplus using the uniporter (UP)

channel. According to Brookes et al. (2004), the UP ion uptake is dependent on the membrane potential, so the movement of charges due to the uptake of calcium consumes the membrane potential that was formed. Furthermore, ABA-induced mitochondrial dysfunction reduces cellular ATP levels and can promote in other organelles such as endoplasmic reticulum, the inactivation of the pump responsible for the maintenance of the Ca2+ ion gradient in the cytoplasm. Invariably, the result of inhibition of the transport system is the disruption of intracellular calcium homeostasis. The increase in intracellular Ca2+ can activate proteases, phospholipases and ion-dependent endonucleases (Trump and Berzesky, 1992). The activation of proteases and phospholipases induces changes in the cytoskeleton and plasma membrane. When selleck chemicals combined, these processes culminate in the disruption of cytoskeleton-plasma membrane interactions,

which results in destabilization of the lipid bilayer, bleb formation on the cell surface and, in more severe cases, leakage and cellular necrosis (Nicotera et al., 1986, Gores et al., 1990 and Sakaida et al., 1992). The enzymes ALT and AST are used as indicators of damage

to hepatic parenchymal cells (Klaassen and Eaton, 1991 and Kaplowitz, 2001). According to Grisham (1979), an efflux of these enzymes in the liquid incubation of cells in not culture indicates that there was a loss of membrane integrity. However, this efflux is not only associated with cell death and lysis but also with modifications that can be reversible (Grisham and Smith, 1984). ABA increased the concentration of ALT and AST in the liquid incubation of hepatocytes, and this effect was also influenced by pre-incubation of the cells with proadifen. The changes observed in the release of these enzymes may be a reflection of the influence of ABA on mitochondrial activity. A decrease in the efficiency of energy production by the organelle affects cellular functions that are dependent on energy, and the disruption of these functions may result in cell death (Nicotera et al., 1998, Wallace and Starkov, 2000 and Szewczyk and Wojtczak, 2002). In in vivo studies performed by Lowenstein et al., 1996 and Hsu et al., 2001, ABA caused an elevation in the concentration of the AST in blood serum. El-Shenawy (2010) performed an in vitro study with isolated rat hepatocytes to compare the toxic action of several insecticides.