Genistein Protects against Acetaldehyde-Induced Oxidative Stress and Hepatocyte Injury in Chronic Alcohol-Fed Mice

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 administrationrestored 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.

Automated summary

This study demonstrated that genistein has a protective role in acetaldehyde-induced liver injury in ALD. It ameliorates alcohol-induced hepatic steatosis, injury, and inflammation by reducing oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and hepatocellular apoptosis. The restoration of heme oxygenase-1 (HO-1) levels and involvement of hepatic nuclear factor erythroid 2-related factor 2 (NRF2) were found to be the mechanisms behind genistein's protective effects.