ArticleThe American journal of pathology2008
Zinc supplementation enhances hepatic regeneration by preserving hepatocyte nuclear factor-4alpha in mice subjected to long-term ethanol administration.
Article in The American journal of pathology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- A randomized clinical study to evaluate the possible antifibrotic effect of zinc sulfate in chronic HCV patient receiving direct-acting anti-viral therapy.Inflammopharmacology · 2025Trial
- Randomized trial of anakinra plus zinc vs. prednisone for severe alcohol-associated hepatitis.Journal of hepatology · 2024Trial
- Metallo-herb complexes as emerging therapeutics: chemistry, synthesis approaches, and pharmacological insights.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Zinc sulfate gel reshapes the wound microenvironment to promote full-thickness wound healing in mice.Regenerative therapy · 2025Article
- Dietary Zn Deficiency Inhibits Cell Proliferation via the GPR39-Mediated Suppression of the PI3K/AKT/mTOR Signaling Pathway in the Jejunum of Broilers.Animals : an open access journal from MDPI · 2024Article
- Article
- Zinc Supplementation Prevented Type 2 Diabetes-Induced Liver Injury Mediated by the Nrf2-MT Antioxidative Pathway.Journal of diabetes research · 2021Article
- Hepatic ZIP8 deficiency is associated with disrupted selenium homeostasis, liver pathology, and tumor formation.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Zinc deficiency as a mediator of toxic effects of alcohol abuse.European journal of nutrition · 2018Review
- Regression of Nonalcoholic Fatty Liver Disease with Zinc and Selenium Co-supplementation after Disease Progression in Rats.Iranian journal of medical sciences · 2018Article
- Role of Zinc in the Development/Progression of Alcoholic Liver Disease.Current treatment options in gastroenterology · 2017Review
- Alcoholic and non-alcoholic steatohepatitis.Experimental and molecular pathology · 2014Review
- New advances in molecular mechanisms and emerging therapeutic targets in alcoholic liver diseases.World journal of gastroenterology · 2014Review
- Preservation of hepatocyte nuclear factor-4α contributes to the beneficial effect of dietary medium chain triglyceride on alcohol-induced hepatic lipid dyshomeostasis in rats.Alcoholism, clinical and experimental research · 2013Article
- The zinc transporter Zip14 influences c-Met phosphorylation and hepatocyte proliferation during liver regeneration in mice.Gastroenterology · 2012Article
- Zinc and liver disease.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2012Review
- Histone modifications and alcohol-induced liver disease: are altered nutrients the missing link?World journal of gastroenterology · 2011Review
- Decreased zinc and increased copper in individuals with anxiety.Nutrition and metabolic insights · 2011Article
- Inactivation of hepatocyte nuclear factor-4{alpha} mediates alcohol-induced downregulation of intestinal tight junction proteins.American journal of physiology. Gastrointestinal and liver physiology · 2010Article
- Decreased Serum Hepatocyte Growth Factor (HGF) in Individuals with Bipolar Disorder Normalizes after Zinc and Anti-oxidant Therapy.Nutrition and metabolic insights · 2010Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 3 countries.
Funding
Abstract
Alcoholic liver disease is associated with sustained liver damage and impaired regeneration, as well as significant zinc deficiency. This study was undertaken to examine whether dietary zinc supplementation could improve liver regeneration by increasing the expression of genes involved in hepatic cellular proliferation in a mouse model of alcoholic liver disease. Adult 129S6 mice fed an ethanol-containing liquid diet for 6 months developed alcoholic liver disease as measured by serum alanine transferase activity and histopathological changes. Zinc supplementation to ethanol-exposed mice enhanced liver regeneration as indicated by increased numbers of proliferation cell nuclear antigen (PCNA)-positive and bromodeoxyuridine (BrdU)-labeled hepatocytes. Zinc-enhanced liver regeneration was associated with an increase in hepatocyte nuclear factor-4alpha (HNF-4alpha), a liver-enriched, zinc-finger transcription factor. Studies using cultured HepG2 cells showed that zinc deficiency suppressed cell proliferation and cell proliferation-related proteins, including hepatocyte growth factor (HGF), insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 1 (IGFBP1), metallothionein (MT), and cyclin D1, as well as HNF-4alpha. HNF-4alpha gene silencing inhibited cell proliferation in association with decreased protein levels of IGF-I, IGFBP1, MT, and cyclin D1. The present study provides evidence that zinc supplementation enhances liver regeneration at least in part by HNF-4alpha through the up-regulation of cell proliferation-related proteins, suggesting that dietary zinc supplementation may have beneficial effects in alcoholic liver disease.
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Registered trials
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.