Zinc prevention and treatment of alcoholic liver disease

Yujian Kang, Zhanxiang Zhou

Research output: Contribution to journalReview article

73 Citations (Scopus)

Abstract

Alcoholic liver disease (ALD) is associated with decreases in zinc (Zn) and its major binding protein, metallothionein (MT), in the liver. Studies using animal models have shown that Zn supplementation prevents alcohol-induced liver injury under both acute and chronic alcohol exposure conditions. There are hepatic and extrahepatic actions of Zn in the prevention of alcoholic liver injury. Zn supplementation attenuates ethanol-induced hepatic Zn depletion and suppresses ethanol-elevated cytochrome P450 2E1 (CYP2E1) activity, but increases the activity of alcohol dehydrogenase in the liver; an action that is likely responsible for Zn suppression of alcohol-induced oxidative stress. Zn also enhances glutathione-related antioxidant capacity in the liver. At the cellular level, Zn inhibits alcohol-induced hepatic apoptosis partially through suppression of the Fas/FasL-mediated pathway. Zn supplementation preserves intestinal integrity and prevents endotoxemia, leading to inhibition of endotoxin-induced tumor necrosis factor-α (TNF-α) production in the liver. Zn also directly inhibits the signaling pathway involved in endotoxin-induced TNF-α production. These hepatic and extrahepatic effects of Zn are independent of MT. However, low levels of MT in the liver sensitize the organ to alcohol-induced injury, and elevation of MT enhances the endogenous Zn reservoir and makes Zn available when oxidative stress is imposed. Zn has a high potential to be developed as an effective agent in the prevention and treatment of ALD.

Original languageEnglish (US)
Pages (from-to)391-404
Number of pages14
JournalMolecular Aspects of Medicine
Volume26
Issue number4-5 SPEC. ISS.
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

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Alcoholic Liver Diseases
Liver
Zinc
Metallothionein
Alcohols
Oxidative stress
Endotoxins
Wounds and Injuries
Oxidative Stress
Ethanol
Tumor Necrosis Factor-alpha
Cytochrome P-450 CYP2E1
Endotoxemia
Alcohol Dehydrogenase
Glutathione
Carrier Proteins

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Zinc prevention and treatment of alcoholic liver disease. / Kang, Yujian; Zhou, Zhanxiang.

In: Molecular Aspects of Medicine, Vol. 26, No. 4-5 SPEC. ISS., 01.08.2005, p. 391-404.

Research output: Contribution to journalReview article

Kang, Yujian ; Zhou, Zhanxiang. / Zinc prevention and treatment of alcoholic liver disease. In: Molecular Aspects of Medicine. 2005 ; Vol. 26, No. 4-5 SPEC. ISS. pp. 391-404.
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