Oxidative stress during acetaminophen hepatotoxicity: Sources, pathophysiological role and therapeutic potential

Acetaminophen (APAP) hepatotoxicity is characterized by an extensive oxidative stress. However, its source, pathophysiological role and possible therapeutic potential if targeted, have been controversially described. Earlier studies argued for cytochrome P450-generated reactive oxygen species (ROS) during APAP metabolism, which resulted in massive lipid peroxidation and subsequent liver injury. However, subsequent studies convincingly challenged this assumption and the current paradigm suggests that mitochondria are the main source of ROS, which impair mitochondrial function and are responsible for cell signaling resulting in cell death. Although immune cells can be a source of ROS in other models, no reliable…

• NI
  National Institutes of Health

  Awards: R01 AA12916, R01 DK102142
• UO
  University of Kansas Medical Center
• NI
  National Institute of General Medical Sciences

  Award: 8 P20 GM103549-09 and 1P30 GM118247-01