NRF2 ACTIVATOR DIMETHYL FUMARATE DIMINISHED STEATOSIS, INFLAMMATION AND LIPID PEROXIDATION IN THE LIVER OF BINGE ETHANOL-TREATED RATS.

Objective: This study was conducted to explore the impact of dimethyl fumarate (DMF), which has antioxidant and anti-inflammatory effects, on binge ethanol (EtOH)-induced hepatic steatosis, inflammation, and lipid peroxidation in rats. Material and Method: To examine the potential protective effect of DMF against EtOH-induced hepatic damage, rats were divided into four groups control, DMF, EtOH, and DMF+EtOH. Rats were administered EtOH (4.5 g/kg orally, 3 doses with 12-h intervals). DMF (30 mg/kg; gavage) was applied to rats one hour before each application of EtOH in the DMF+EtOH group. Serum markers of liver damage, triglyceride (TG), tumor necrosis factor-alpha (TNF-α), lipid and protein oxidation products, myeloperoxidase (MPO), and antioxidant enzymes together with histopathological examinations were performed in liver tissue. Protein expressions associated with antioxidant mechanism (nuclear factor erythroid 2-related factor; Nrf2 and heme oxygenase-1; HO-1), lipid metabolism (sterol regulatory element-binding protein-1c; SREBP-1c and peroxisome proliferator-activated receptor-alpha; PPAR-α), oxidative stress (cytochrome P4502E1; CYP2E1), and inflammation (nuclear factor-kappa B; NF-κB) were also investigated in the rats’ livers. Result: DMF reduced elevated levels of serum markers of liver damage and hepatic TG, TNF-α and reactive oxygen species levels, lipid and protein oxidation products, and MPO activity together with the alleviation of histopathological lesions in EtOH-treated rats. Increased Nrf2 and HO-1 and decreased SREBP-1c and CYP2E1 expressions were also detected in the DMF+EtOH group compared with the EtOH group. Conclusion: Our results demonstrate that DMF may provide a protective effect against EtOH-induced hepatic lesions. These outcomes may be linked to the anti-oxidative, anti-inflammatory, and anti-lipogenic potential of DMF-induced Nrf2 activation. [ABSTRACT FROM AUTHOR]