N-acetylcysteine protects against liver injure induced by carbon tetrachloride via activation of the Nrf2/HO-1 pathway.
Chronic liver injury is an important clinical problem which eventually leads to cirrhosis, hepatocellular carcinoma and end-stage liver failure. It is well known that cell damage induced by reactive oxygen species (ROS) is an important mechanism of hepatocyte injure. N-acetylcysteine (NAC), a precursor of glutathione (GSH), is well-known role as the antidote to acetaminophen toxicity in clinic. NAC is now being utilized more widely in the clinical setting for non-acetaminophen (APAP) related causes of liver injure. However, the mechanisms underlying its beneficial effects are poorly defined. Thus, Aim of the present study was to investigate potential hepatic protective role of NAC and to delineate its mechanism of action against carbon tetrachloride (CCl4)-induced liver injury in models of rat. Our results showed that the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as malondialdehyde (MDA) contents decreased significantly in CCl4-induced rats with NAC treatment. GSH content and superoxide dismutase (SOD) activities remarkably increased in the NAC groups compared with those in CCl4-induced group. Treatment with NAC had been shown to an increase in nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA levels. In conclusion, these results suggested that NAC upregulated HO-1 through the activation of Nrf2 pathway and protected rat against CCl4-induced liver injure. The results of this study provided pharmacological evidence to support the clinical application of NAC.
Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese Medicine Hangzhou, Zhejiang, People's Republic of China.
Zhaobin
Z
Cai
Zhejiang Academy of Medical Sciences Hangzhou, Zhejiang, People's Republic of China.
Qi
Q
Lou
Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese Medicine Hangzhou, Zhejiang, People's Republic of China.
Fugen
F
Wang
Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese Medicine Hangzhou, Zhejiang, People's Republic of China.
Er
E
Li
Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese Medicine Hangzhou, Zhejiang, People's Republic of China.
Jingjing
J
Sun
Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese Medicine Hangzhou, Zhejiang, People's Republic of China.
Hongying
H
Fang
Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese Medicine Hangzhou, Zhejiang, People's Republic of China.
Jianjun
J
Xi
Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese Medicine Hangzhou, Zhejiang, People's Republic of China.
Liping
L
Ju
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D019610:Cytoprotection; D004195:Disease Models, Animal; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation
D000975:Antioxidants; D015415:Biomarkers; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D012333:RNA, Messenger; D002251:Carbon Tetrachloride; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D000111:Acetylcysteine
N-acetylcysteine; Nrf2/HO-1 pathway; carbon tetrachloride; liver injure; oxidative stress