Treatment with dimethyl fumarate ameliorates liver ischemia/reperfusion injury

AIM To investigate the hypothesis that treatment with dimethyl fumarate(D MF) mayame liorate 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 × 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 μmol/L vs CTL 26.0 ± 1.0 μmol/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 m U/m L vs CTL 6.0 ± 0.5 m U/m L, 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.