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Anti-steatotic and anti-fibrotic effects of the KCa3.1 channel inhibitor, Senicapoc, in non-alcoholic liver disease 预览
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作者 Latha Paka David E Smith +10 位作者 Dawoon Jung Siobhan McCormack Ping Zhou Bin Duan Jing-Song Li Jiaqi Shi Yong-Jie Hao Kai Jiang Michael Yamin Itzhak D Goldberg Prakash Narayan 《世界胃肠病学杂志:英文版》 SCIE CAS 2017年第23期4181-4190,共10页
AIM To evaluate a calcium activated potassium channel(KCa3.1) inhibitor attenuates liver disease in models of non-alcoholic fatty liver disease(NAFLD).METHODS We have performed a series of in vitro and in vivo studies... AIM To evaluate a calcium activated potassium channel(KCa3.1) inhibitor attenuates liver disease in models of non-alcoholic fatty liver disease(NAFLD).METHODS We have performed a series of in vitro and in vivo studies using the KCa3.1 channel inhibitor, Senicapoc. Efficacy studies of Senicapoc were conducted in toxin-, thioacetamide(TAA) and high fat diet(HFD)-induced models of liver fibrosis in rats. Efficacy and pharmacodynamic effects of Senicapoc was determined through biomarkers of apoptosis, inflammation, steatosis and fibrosis. RESULTS Upregulation of KCa3.1 expression was recorded in TAA-induced and high fat diet-induced liver disease. Treatment with Senicapoc decreased palmitic aciddriven Hep G2 cell death.(P < 0.05 vs control) supporting the finding that Senicapoc reduces lipiddriven apoptosis in Hep G2 cell cultures. In animals fed a HFD for 6 wk, co-treatment with Senicapoc,(1) reduced non-alcoholic fatty liver disease(NAFLD) activity score(NAS)(0-8 scale),(2) decreased steatosis and(3) decreased hepatic lipid content(Oil Red O, P < 0.05 vs vehicle). Randomization of TAA animals and HFD fed animals to Senicapoc was associated with a decrease in liver fibrosis as evidenced by hydroxyproline and Masson’s trichrome staining(P < 0.05 vs vehicle). These results demonstrated that Senicapoc mitigates both steatosis and fibrosis in liver fibrosis models.CONCLUSION These data suggest that Senicapoc interrupts more than one node in progressive fatty liver disease by its anti-steatotic and anti-fibrotic activities, serving as a double-edged therapeutic sword. 展开更多
关键词 高胖的饮食 脂肪变性 纤维变性 KCa3.1 隧道 Senicapoc 发炎
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