PMID- 36653166 OWN - NLM STAT- MEDLINE DCOM- 20230202 LR - 20230202 IS - 1520-5118 (Electronic) IS - 0021-8561 (Linking) VI - 71 IP - 4 DP - 2023 Feb 1 TI - Genistein Protects against Acetaldehyde-Induced Oxidative Stress and Hepatocyte Injury in Chronic Alcohol-Fed Mice. PG - 1930-1943 LID - 10.1021/acs.jafc.2c05747 [doi] AB - 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. FAU - Ding, Qinchao AU - Ding Q AUID- ORCID: 0000-0001-8664-5368 AD - School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, P. R. China. AD - College of Animal Science, Zhejiang University, Hangzhou 310058, Zhejiang, P. R. China. FAU - Pi, Aiwen AU - Pi A AD - School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, P. R. China. FAU - Hao, Liuyi AU - Hao L AD - School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, P. R. China. FAU - Xu, Tiantian AU - Xu T AD - School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, P. R. China. FAU - Zhu, Qin AU - Zhu Q AD - Department of Clinical Nutrition, Affiliated Zhejiang Hospital, School of Medicine, Zhejiang University, Hangzhou 310013, Zhejiang, P. R. China. FAU - Shu, Long AU - Shu L AD - Department of Clinical Nutrition, Affiliated Zhejiang Hospital, School of Medicine, Zhejiang University, Hangzhou 310013, Zhejiang, P. R. China. FAU - Yu, Xiaolong AU - Yu X AD - Department of Clinical Nutrition, Affiliated Zhejiang Hospital, School of Medicine, Zhejiang University, Hangzhou 310013, Zhejiang, P. R. China. FAU - Wang, Weiguang AU - Wang W AD - Department of Clinical Nutrition, Affiliated Zhejiang Hospital, School of Medicine, Zhejiang University, Hangzhou 310013, Zhejiang, P. R. China. FAU - Si, Caijuan AU - Si C AD - Department of Clinical Nutrition, Affiliated Zhejiang Hospital, School of Medicine, Zhejiang University, Hangzhou 310013, Zhejiang, P. R. China. FAU - Li, Songtao AU - Li S AUID- ORCID: 0000-0002-2926-673X AD - School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, P. R. China. AD - Department of Clinical Nutrition, Affiliated Zhejiang Hospital, School of Medicine, Zhejiang University, Hangzhou 310013, Zhejiang, P. R. China. LA - eng PT - Journal Article DEP - 20230118 PL - United States TA - J Agric Food Chem JT - Journal of agricultural and food chemistry JID - 0374755 RN - GO1N1ZPR3B (Acetaldehyde) RN - DH2M523P0H (Genistein) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - 0 (NF-E2-Related Factor 2) RN - 3K9958V90M (Ethanol) SB - IM MH - Mice MH - Animals MH - *Acetaldehyde/metabolism MH - *Genistein/metabolism MH - Heme Oxygenase-1/genetics/metabolism MH - NF-E2-Related Factor 2/genetics/metabolism MH - Ethanol/metabolism MH - Hepatocytes/metabolism MH - Liver/metabolism MH - Oxidative Stress OTO - NOTNLM OT - acetaldehyde OT - alcohol-related liver disease OT - genistein OT - inflammation OT - oxidative stress EDAT- 2023/01/19 06:00 MHDA- 2023/02/03 06:00 CRDT- 2023/01/18 21:22 PHST- 2023/01/19 06:00 [pubmed] PHST- 2023/02/03 06:00 [medline] PHST- 2023/01/18 21:22 [entrez] AID - 10.1021/acs.jafc.2c05747 [doi] PST - ppublish SO - J Agric Food Chem. 2023 Feb 1;71(4):1930-1943. doi: 10.1021/acs.jafc.2c05747. Epub 2023 Jan 18.