ArticleJournal of hepatology2015
Pharmacological activation of aldehyde dehydrogenase 2 by Alda-1 reverses alcohol-induced hepatic steatosis and cell death in mice.
Article in Journal of hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 98 citations in OpenAlex.
- Diurnal Regulation and Gene-Specific Vulnerability of Oxidative Alcohol-Metabolizing Enzymes to Circadian Disruption.International journal of molecular sciences · 2026Article
- ALDH2 in autophagy and cell death: molecular mechanisms and implications for diseases.Military Medical Research · 2025Review
- Not 'Inactive' After All: Cardiotoxic Mechanisms of Catecholamine Metabolism by Monoamine Oxidase.Cardiovascular toxicology · 2025Review
- ACSS2 protects against alcohol-induced hepatocyte ferroptosis through regulation of hepcidin expression.Nature communications · 2025Article
- Hepatic NMNAT1 is required to defend against alcohol-associated fatty liver disease.Science advances · 2025Article
- The Pathological Role and Therapeutic potential of ALDH2 in acrolein detoxification Following Spinal Cord Injury in Mice.bioRxiv : the preprint server for biology · 2025Article
- Alcohol-Metabolizing Enzymes, Liver Diseases and Cancer.Seminars in liver disease · 2025Review
- Nobiletin protects against alcohol-induced mitochondrial dysfunction and liver injury by regulating the hepatic NRF1-TFAM signaling pathway.Redox report : communications in free radical research · 2024Article
- Reversal of hepatic accumulation of nordeoxycholic acid underlines the beneficial effects of cholestyramine on alcohol-associated liver disease in mice.Hepatology communications · 2024Article
- Recent insights into the pathogenesis and therapeutic targets of chronic liver diseases.eGastroenterology · 2023Article
- A common East-Asian ALDH2 mutation causes metabolic disorders and the therapeutic effect of ALDH2 activators.Nature communications · 2023Article
- Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease.Journal of translational medicine · 2023Review
- p53 protects against alcoholic fatty liver disease via ALDH2 inhibition.The EMBO journal · 2023Article
- Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets.MedComm · 2023Review
- Loss of long-chain acyl-CoA synthetase 1 promotes hepatocyte death in alcohol-induced steatohepatitis.Metabolism: clinical and experimental · 2023Article
- Promoting intestinal antimicrobial defense and microbiome symbiosis contributes to IL-22-mediated protection against alcoholic hepatitis in mice.Frontiers in immunology · 2023Article
- Hepatitis B virus X protein induces ALDH2 ubiquitin-dependent degradation to enhance alcoholic steatohepatitis.Gastroenterology report · 2023Article
- The potential effects of HECTD4 variants on fasting glucose and triglyceride levels in relation to prevalence of type 2 diabetes based on alcohol intake.Archives of toxicology · 2022Article
- Activation of aldehyde dehydrogenase 2 protects ethanol-induced osteonecrosis of the femoral head in rat model.Cell proliferation · 2022Article
- Hydroxynonenal Causes Hepatocyte Death by Disrupting Lysosomal Integrity in Nonalcoholic Steatohepatitis.Cellular and molecular gastroenterology and hepatology · 2022Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsEffective therapies for alcoholic liver disease are currently unavailable. The present study tested the efficacy of Alda-1, a specific aldehyde dehydrogenase 2 (ALDH2) activator, in treating alcoholic liver disease.
methodsMale C57BL/6J mice were exposed to alcohol for a time-course study on aldehyde metabolism. The specificity and efficacy of Alda-1 on activating hepatic ALDH2 and aldehyde clearance were determined by acute treatments. Then, mice were fed alcohol for 8 weeks with Alda-1 administration for the last 10 days to test the therapeutic potential of Alda-1. Lastly, H4IIEC3 cells were treated with ethanol, acetaldehyde, or 4-hydroxynonenal to define the link between aldehydes and hepatotoxicity.
resultsAlcohol feeding for 8 weeks induced hepatic ALDH2 dysfunction and aldehyde accumulation. One dose of Alda-1 administration elevated hepatic ALDH activity, which was blocked by the specific ALDH2 inhibitor, daidzin. Alda-1 accelerated acetaldehyde clearance after acute alcohol intoxication. Alda-1 treatment in the 8-week alcohol feeding model reversed liver damage along with reduction of hepatic aldehydes. Alda-1 re-activated transcription factors, upregulated fatty acid oxidation enzymes, and reversed steatosis. Alcohol-induced endoplasmic reticulum stress and apoptotic cell death were also attenuated by Alda-1. Acetaldehyde or 4-hydroxynonenal treatment to H4IIEC3 cells inactivated transcription factors and induced endoplasmic reticulum stress and apoptosis, while ethanol per se showed limited effects.
conclusionsPharmacological activation of ALDH2 by Alda-1 reversed alcoholic steatosis and apoptosis through accelerating aldehyde clearance. This study indicates that ALDH2 is a promising molecular target and Alda-1 has therapeutic potential for treating alcoholic liver disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.