Arsenic-Induced Injury of Mouse Hepatocytes through Lysosome and Mitochondria: An In Vitro Study

Figure 7

Schematic diagram of the proposed cellular events during arsenic exposure to hepatocytes. Arsenic exposure to hepatocyte causes activation of plasma membrane-bound NOX and generation of ROS in the cell. Both ROS and arsenic cause leakage of lysosomal membrane leading to LMP resulting in release of cathepsin B and increased ROS generation. Both cathepsin B and increased ROS in turn cause mitochondrial changes leading to rapid onset of MPT that is upstream of cytochrome c release as well as increase in BAX and BCL-2 ratio. Cytochrome c further promotes the effector caspase activation leading to apoptotic death of hepatocytes. Increased ROS causes induction of ER stress at a later time period, and the role of ER stress in mitochondrial functional changes in our study is debatable.