title: Curcumin attenuates chronic ethanol-induced liver injury by inhibition of oxidative stress via mitogen-activated protein kinase/nuclear factor E2-related factor 2 pathway in mice.
abstract: OBJECTIVE
  This study aimed to investigate the protective effect of curcumin on chronic ethanol-induced liver injury in mice and to explore its underlying mechanisms.
  
  
  METHODS
  Ethanol-exposed Balb/c mice were simultaneously treated with curcumin for 6 weeks. Liver injury was evaluated by biochemical and histopathological examination. Lipid peroxidation and anti-oxidant activities were measured by spectrophotometric method. Anti-oxidative genes expression such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and superoxide dismutase (SOD) were determined by real-time polymerase chain reaction. The nuclear factor E2-related factor 2 (Nrf2) and the phosphorylation states of specific proteins central to intracellular signaling cascades were measured by western blotting.
  
  
  RESULTS
  Curcumin treatment protected liver from chronic ethanol-induced injury through reducing serum alanine aminotransferase and aspartate aminotransferase activities, improving liver histological architecture, and reversing lipid disorders indicated by decrease of triglyceride, total cholesterol and low-density lipoprotein-cholesterol levels and increase of High-density lipoprotein-cholesterol levels. Meanwhile, curcumin administration attenuated oxidative stress via up-regulating SOD and glutathione peroxidase activities, leading to a reduction of lipid hydroperoxide production. In addition, curcumin increased Nrf2 activation and anti-oxidative genes expressions such as NQO1, HO-1, and SOD through inducing extracellular signal-regulated kinase (ERK) and p38 phosphorylation.
  
  
  CONCLUSIONS
  Our data suggested that curcumin protected the liver from chronic-ethanol induced injury through attenuating oxidative stress, at least partially, through ERK/p38/Nrf2-mediated anti-oxidant signaling pathways.
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Zhang E
authors.initials: ZE
authors.lastname: Xiong
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Wei Guo
authors.initials: WG
authors.lastname: Dong
authors.affiliation: Department of Pharmacology, Henan College of Chinese Traditional Medicine, Zhengzhou 450008, Henan Province, China.
authors.forename: Bao Ying
authors.initials: BY
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Institute of Digestive Disease, China Three Gorges University, Yichang 443003, Hubei Province, China.
authors.forename: Qiao Yun
authors.initials: QY
authors.lastname: Tong
authors.affiliation: Department of Gastroenterology, Institute of Digestive Disease, China Three Gorges University, Yichang 443003, Hubei Province, China.
authors.forename: Zhong Yan
authors.initials: ZY
authors.lastname: Li
keywords: Curcumin; liver injury; mitogen-activated protein kinase; nuclear factor E2-related factor 2; oxidative stress