PMID- 25386077 OWN - NLM STAT- MEDLINE DCOM- 20150810 LR - 20211203 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 20 IP - 41 DP - 2014 Nov 7 TI - N-acetylcysteine attenuates reactive-oxygen-species-mediated endoplasmic reticulum stress during liver ischemia-reperfusion injury. PG - 15289-98 LID - 10.3748/wjg.v20.i41.15289 [doi] AB - 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. FAU - Sun, Yong AU - Sun Y AD - Yong Sun, Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China. FAU - Pu, Li-Yong AU - Pu LY AD - Yong Sun, Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China. FAU - Lu, Ling AU - Lu L AD - Yong Sun, Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China. FAU - Wang, Xue-Hao AU - Wang XH AD - Yong Sun, Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China. FAU - Zhang, Feng AU - Zhang F AD - Yong Sun, Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China. FAU - Rao, Jian-Hua AU - Rao JH AD - Yong Sun, Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (Antioxidants) RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (Hspa5 protein, mouse) RN - 0 (Reactive Oxygen Species) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/*pharmacology MH - Animals MH - Antioxidants/*pharmacology MH - Apoptosis/drug effects MH - Cells, Cultured MH - Cytoprotection MH - Disease Models, Animal MH - Endoplasmic Reticulum/*drug effects/metabolism/pathology MH - Endoplasmic Reticulum Chaperone BiP MH - Endoplasmic Reticulum Stress/*drug effects MH - Liver/*blood supply/*drug effects/metabolism/pathology MH - Liver Diseases/*drug therapy/metabolism/pathology MH - Male MH - Mice, Inbred C57BL MH - Oxidative Stress/*drug effects MH - Reactive Oxygen Species/*metabolism MH - Reperfusion Injury/*drug therapy/metabolism/pathology MH - Signal Transduction/drug effects PMC - PMC4223262 OTO - NOTNLM OT - Apoptosis OT - Endoplasmic reticulum stress OT - Liver ischemia-reperfusion OT - N-acetylcysteine OT - Reactive oxygen species EDAT- 2014/11/12 06:00 MHDA- 2015/08/11 06:00 PMCR- 2014/11/07 CRDT- 2014/11/12 06:00 PHST- 2013/02/11 00:00 [received] PHST- 2014/04/08 00:00 [revised] PHST- 2014/06/26 00:00 [accepted] PHST- 2014/11/12 06:00 [entrez] PHST- 2014/11/12 06:00 [pubmed] PHST- 2015/08/11 06:00 [medline] PHST- 2014/11/07 00:00 [pmc-release] AID - 10.3748/wjg.v20.i41.15289 [doi] PST - ppublish SO - World J Gastroenterol. 2014 Nov 7;20(41):15289-98. doi: 10.3748/wjg.v20.i41.15289.