染料木素
乙醛
氧化应激
酒精性肝病
肝损伤
乙醇代谢
化学
肝细胞
内分泌学
血红素加氧酶
醇脱氢酶
内科学
CYP2E1
药理学
血红素
生物化学
医学
乙醇
细胞色素P450
新陈代谢
肝硬化
酶
体外
作者
Qinchao Ding,Aiwen Pi,Liuyi Hao,Tiantian Xu,Qin Zhu,Long Shu,Xiao-Long Yu,Wei-Guang Wang,Caijuan Si,Songtao Li
标识
DOI:10.1021/acs.jafc.2c05747
摘要
Alcohol-related liver disease (ALD) is one of the most prevalent forms of liver disease in the world. Acetaldehyde, an intermediate product of alcohol catabolism, is a cause of liver injury caused by alcohol. This study was designed to evaluate the protective role and mechanism(s) of genistein against acetaldehyde-induced liver injury in the pathological process of ALD. We found that genistein administration significantly ameliorated alcohol-induced hepatic steatosis, injury, and inflammation in mice. Genistein supplementation markedly reversed hepatic oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and hepatocellular apoptosis in both alcohol-fed mice liver and acetaldehyde-treated hepatocytes. The mechanistic experiments revealed that the restoration of genistein administration rescued heme oxygenase-1 (HO-1) reduction at both transcriptional and protein levels in either alcohol-fed mice liver or acetaldehyde-treated hepatocytes, and the beneficial aspects derived from genistein were abolished in antioxidase heme oxygenase-1 (HO-1)-deficient hepatocytes. Moreover, we confirmed that genistein administration-restored hepatic nuclear factor erythroid 2-related factor 2 (NRF2), a key transcriptional regulator of HO-1, was involved in the protective role of genistein in ALD. This study demonstrated that genistein ameliorated acetaldehyde-induced oxidative stress and liver injury by restoring the hepatic NRF2-HO-1 signaling pathway in response to chronic alcohol consumption. Therefore, genistein may serve as a potential therapeutic choice for the treatment of ALD.
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