Anti-steatotic and anti-fibrotic effects of the KCa3.1 channel inhibitor, Senicapoc, in non-alcoholic liver disease
Anti-steatotic and anti-fibrotic effects of the KCa3.1 channel inhibitor, Senicapoc, in non-alcoholic liver disease作者机构：Department of Research and Development Angion Biomedica Corp.
出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)
年 卷 期：2017年第23卷第23期
页 面：4181-4190页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
主 题：高胖的饮食 肝 脂肪变性 纤维变性 KCa3.1 隧道 Senicapoc 发炎
摘 要：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 *** 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.
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