N-acetylcysteine attenuates reactive-oxygen-species-mediated endoplasmic reticulum stress during liver ischemia-reperfusion injury.
OBJECTIVE
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.


CONCLUSIONS
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.
Yong Sun, Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
Yong
Y
Sun
Yong Sun, Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
Li-Yong
LY
Pu
Yong Sun, Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
Ling
L
Lu
Yong Sun, Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
Xue-Hao
XH
Wang
Yong Sun, Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
Feng
F
Zhang
Yong Sun, Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
Jian-Hua
JH
Rao
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
D000975:Antioxidants; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D017382:Reactive Oxygen Species; D000111:Acetylcysteine
Apoptosis; Endoplasmic reticulum stress; Liver ischemia-reperfusion; N-acetylcysteine; Reactive oxygen species