Treatment with dimethyl fumarate ameliorates liver ischemia/reperfusion injury.

AIM To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). METHODS Rats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate (ATP), NO x metabolites, anti-oxidant enzyme expression level, antiinflammatory effect, and anti-apoptotic effect were determined. RESULTS Histological tissue damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 +/- 0; CTL: 9.3 +/- 0.5; DMF: 2.5 +/- 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 +/- 2305 U/L vs CTL 10592 +/- 1152 U/L, P = 0.04) and MDA (DMF 18.2 +/- 1.4 mu mol/L vs CTL 26.0 +/- 1.0 mu mol/L, P = 0.0009). DMF effectively improved the ATP content (DMF 20.3 +/- 0.4 nmol/mg vs CTL 18.3 +/- 0.6 nmol/mg, P = 0.02), myeloperoxidase activity (DMF 7.8 +/- 0.4 mU/mL vs CTL 6.0 +/- 0.5 mU/mL, P = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 +/- 0.05-fold vs 0.17 +/- 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamatecysteine ligase modifier subunit and lower levels of key inflammatory mediators (nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group. CONCLUSION DMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI.