Effects of oral intake of hydrogen water on liver fibrogenesis in mice
Effects of oral intake of hydrogen water on liver fibrogenesis in mice
复制标题
DOI：
10.1111/hepr.12165
复制
发表时间：
2014-06-01
影响因子：
4.2
通讯作者：
Uemoto, Shinji
中科院分区：
文献类型：
--
作者：
Koyama, Yukinori;Taura, Kojiro;Uemoto, Shinji
目的肝纤维化是慢性肝病的普遍后果。持续的肝细胞损伤引发炎症反应，从而激活肝星状细胞，肝中主要的纤维化细胞。活性氧参与肝损伤，是治疗肝纤维化的一个有前途的靶点。据报道，氢水具有作为活性氧相关疾病的治疗工具的潜力。本研究旨在探讨氢水对肝纤维化的影响及其作用机制。方法C57 BL/6小鼠分别用氢水和对照水灌胃，用四氯化碳、硫代乙酰胺和胆管结扎诱导肝纤维化。从小鼠中分离肝细胞和肝星状细胞，并在有或没有氢气的情况下培养，以测试氢气对活性氧诱导的肝细胞损伤或肝星状细胞活化的影响。结果口服氢水可明显抑制四氯化碳和硫代乙酰胺模型大鼠肝纤维化的形成，但对胆管结扎模型无明显影响。用1g/mL抗霉素A处理离体肝细胞产生羟自由基。在富氢培养基中培养选择性地抑制肝细胞中羟基自由基的产生，并显着抑制抗霉素A诱导的肝细胞死亡，但是，它没有抑制肝星状细胞活化。结论氢水通过清除羟自由基保护肝细胞，从而抑制肝纤维化的发生。
Aim Liver fibrosis is the universal consequence of chronic liver diseases. Sustained hepatocyte injury initiates an inflammatory response, thereby activating hepatic stellate cells, the principal fibrogenic cells in the liver. Reactive oxygen species are involved in liver injury and are a promising target for treating liver fibrosis. Hydrogen water is reported to have potential as a therapeutic tool for reactive oxygen species-associated disorders. This study aimed to investigate the effects of hydrogen water on liver fibrogenesis and the mechanisms underlying these effects. Methods C57BL/6 mice were fed with hydrogen water or control water, and subjected to carbon tetrachloride, thioacetamide and bile duct ligation treatments to induce liver fibrosis. Hepatocytes and hepatic stellate cells were isolated from mice and cultured with or without hydrogen to test the effects of hydrogen on reactive oxygen species-induced hepatocyte injuries or hepatic stellate cell activation. Results Oral intake of hydrogen water significantly suppressed liver fibrogenesis in the carbon tetrachloride and thioacetamide models, but these effects were not seen in the bile duct ligation model. Treatment of isolated hepatocyte with 1g/mL antimycin A generated hydroxyl radicals. Culturing in the hydrogen-rich medium selectively suppressed the generation of hydroxyl radicals in hepatocytes and significantly suppressed hepatocyte death induced by antimycin A; however, it did not suppress hepatic stellate cell activation. Conclusion We conclude that hydrogen water protects hepatocytes from injury by scavenging hydroxyl radicals and thereby suppresses liver fibrogenesis in mice.