Yin-Kuang Chang1, Su-Cheng Huang1, Ming-Chang Kao2, Chun-Jen Huang3. 1. Department of Obstetrics/Gynecology, Taipei Tzu Chi Hospital, Taipei, Taiwan. 2. Department of Anesthesiology, Taipei Tzu Chi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan. 3. Department of Anesthesiology, Taipei Tzu Chi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan. Electronic address: huangcj1112@gmail.com.
Abstract
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.
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.
Authors: Eliza W Beal; Curtis Dumond; Jung-Lye Kim; Khalid Mumtaz; Don Hayes; Ken Washburn; Bryan A Whitson; Sylvester M Black Journal: J Vis Exp Date: 2017-04-02 Impact factor: 1.355