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

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. Materials and 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. Conclusion: 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.