Cepharanthine alleviates liver injury in a rodent model of limb ischemia-reperfusion

Objectives: Limb ischemia-reperfusion (I/R) causes remote organ injury (e.g., liver injury). Oxidation and inflammation are crucial mechanisms. We investigated the effects of cepharanthine, a potent antioxidative and anti-inflammatory drug, on alleviating liver injury induced by limb I/R. Methods: Twenty-four adult male Sprague-Dawley rats were randomized to receive sham operation (Sham), Sham plus cepharanthine, I/R, or I/R plus cepharanthine and designated as the Sham, Sham+Cep, I/R, or I/R+Cep group, respectively (n = 6 in each group). I/R was induced by applying rubber band tourniquets high around each hind limb for 3 hours followed by reperfusion for 24 hours. Results: The plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of the Sham and Sham+Cep groups were low, and the levels of AST and ALT of the I/R group were significantly higher than those of the Sham group (both p < 0.001). By contrast, the AST and ALT of the I/R+Cep group were significantly lower than those of the I/R group (both p < 0.001). The hepatic levels of nitric oxide (NO), malondialdehyde (MDA), macrophage inflammatory protein 2 (MIP-2), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2)/prostaglandin E₂ (PGE₂) of the Sham and Sham+Cep groups were also low. As expected, the NO, MDA, MIP-2, IL-6, and COX-2/PGE₂ of the I/R group were significantly higher than those of the Sham group (all p < 0.001). By contrast, the NO, MDA, MIP-2, IL-6, and COX-2/PGE₂ of the I/R+Cep group were significantly lower than those of the I/R group (all p < 0.05). Conclusion: Cepharanthine alleviates liver injury in a rodent model of limb I/R. The mechanisms may involve reducing oxidation and inflammation.