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 × metabolites, anti-oxidant enzyme expression level, anti-inflammatory 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 CTL, < 0.0001; CTL DMF, < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 ± 2305 U/L CTL 10592 ± 1152 U/L, = 0.04) and MDA (DMF 18.2 ± 1.4 μmol/L CTL 26.0 ± 1.0 μmol/L, = 0.0009). DMF effectively improved the ATP content (DMF 20.3 ± 0.4 nmol/mg CTL 18.3 ± 0.6 nmol/mg, = 0.02), myeloperoxidase activity (DMF 7.8 ± 0.4 mU/mL CTL 6.0 ± 0.5 mU/mL, = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 ± 0.05-fold 0.17 ± 0.06-fold, = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamate-cysteine 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504366 | PMC |
| http://dx.doi.org/10.3748/wjg.v23.i25.4508 | DOI Listing |
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