Genistein Protects against Acetaldehyde-Induced Oxidative Stress and Hepatocyte Injury in Chronic Alcohol-Fed Mice. 2023

Qinchao Ding, and Aiwen Pi, and Liuyi Hao, and Tiantian Xu, and Qin Zhu, and Long Shu, and Xiaolong Yu, and Weiguang Wang, and Caijuan Si, and Songtao Li
School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, P. R. China.

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.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D000079 Acetaldehyde A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. Ethanal
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051267 NF-E2-Related Factor 2 A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage. Nfe2l2 Protein,Nuclear Factor (Erythroid-Derived 2)-Like 2 Protein,Nuclear Factor E2-Related Factor 2,NF E2 Related Factor 2,Nuclear Factor E2 Related Factor 2
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051547 Heme Oxygenase-1 A ubiquitous stress-responsive enzyme that catalyzes the oxidative cleavage of HEME to yield IRON; CARBON MONOXIDE; and BILIVERDIN. Hemeoxygenase 1,Heme Oxygenase 1,Oxygenase-1, Heme
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative
D019833 Genistein An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE. Genestein
D022781 Hepatocytes The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules. Hepatic Cells,Cell, Hepatic,Cells, Hepatic,Hepatic Cell,Hepatocyte

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