Published online Nov 7, 2014. doi: 10.3748/wjg.v20.i41.15289
Revised: April 8, 2014
Accepted: June 26, 2014
Published online: November 7, 2014
AIM: To investigate the effects of N-acetylcysteine (NAC) on endoplasmic reticulum (ER) stress and tissue injury during liver ischemia reperfusion injury (IRI).
METHODS: Mice were injected with NAC (300 mg/kg) intraperitoneally 2 h before ischemia. Real-time polymerase chain reaction and western blotting determined ER stress molecules (GRP78, ATF4 and CHOP). To analyze the role of NAC in reactive oxygen species (ROS)-mediated ER stress and apoptosis, lactate dehydrogenase (LDH) was examined in cultured hepatocytes treated by H2O2 or thapsigargin (TG).
RESULTS: NAC treatment significantly reduced the level of ROS and attenuated ROS-induced liver injury after IRI, based on glutathione, malondialdehyde, serum alanine aminotransferase levels, and histopathology. ROS-mediated ER stress was significantly inhibited in NAC-treated mice. In addition, NAC treatment significantly reduced caspase-3 activity and apoptosis after reperfusion, which correlated with the protein expression of Bcl-2 and Bcl-xl. Similarly, NAC treatment significantly inhibited LDH release from hepatocytes treated by H2O2 or TG.
CONCLUSION: This study provides new evidence for the protective effects of NAC treatment on hepatocytes during IRI. Through inhibition of ROS-mediated ER stress, NAC may be critical to inhibit the ER-stress-related apoptosis pathway.
Core tip: The protective effect of N-acetylcysteine (NAC) treatment has been confirmed in IRI; however, its underlying mechanism remains unclear. Our previous data showed that endoplasmic reticulum (ER) stress is critical for the development of liver IRI. We have found new evidence for the protective effects of NAC on hepatocytes during liver IRI. Our data demonstrated that NAC modulates ER stress signaling and reduces ER-stress-mediated apoptosis during liver IRI. These findings provide further support for the usefulness of exploring NAC as a potential alternative drug for treating liver IRI.