Preservation of intestinal structural integrity by zinc is independent of metallothionein in alcohol-intoxicated mice

Jason C. Lambert, Zhanxiang Zhou, Lipeng Wang, Zhenyuan Song, Craig J. McClain, Yujian Kang

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Intestinal-derived endotoxins are importantly involved in alcohol-induced liver injury. Disruption of intestinal barrier function and endotoxemia are common features associated with liver inflammation and injury due to acute ethanol exposure. Zinc has been shown to inhibit acute alcohol-induced liver injury. This study was designed to determine the inhibitory effect of zinc on alcohol-induced endotoxemia and whether the inhibition is mediated by metallothionein (MT) or is independent of MT. MT knockout (MT-KO) mice were administered three oral doses of zinc sulfate (2.5 mg zinc ion/kg body weight) every 12 hours before being administered a single dose of ethanol (6 g/kg body weight) by gavage. Ethanol administration caused liver injury as determined by increased serum transaminases, parenchymal fat accumulation, necrotic foci, and an elevation of tumor necrosis factor (TNT-α). Increased plasma endotoxin levels were detected in ethanol-treated animal whose small intestinal structural integrity was compromised as determined by microscopic examination. Zinc supplementation significantly inhibited acute ethanol-induced liver injury and suppressed hepatic TNF-α production in association with decreased circulating endotoxin levels and a significant protection of small intestine structure. As expected, MT levels remained undetectable in the MT-KO mice under the zinc treatment. These results thus demonstrate that zinc preservation of intestinal structural integrity is associated with suppression of endotoxemia and liver injury induced by acute exposure to ethanol and the zinc protection is independent of MT.

Original languageEnglish (US)
Pages (from-to)1959-1966
Number of pages8
JournalAmerican Journal of Pathology
Volume164
Issue number6
DOIs
StatePublished - Jan 1 2004

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Metallothionein
Zinc
Alcohols
Ethanol
Liver
Endotoxemia
Wounds and Injuries
Endotoxins
Body Weight
Zinc Sulfate
Transaminases
Knockout Mice
Small Intestine
Tumor Necrosis Factor-alpha
Fats
Ions
Inflammation
Serum

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Preservation of intestinal structural integrity by zinc is independent of metallothionein in alcohol-intoxicated mice. / Lambert, Jason C.; Zhou, Zhanxiang; Wang, Lipeng; Song, Zhenyuan; McClain, Craig J.; Kang, Yujian.

In: American Journal of Pathology, Vol. 164, No. 6, 01.01.2004, p. 1959-1966.

Research output: Contribution to journalArticle

Lambert, Jason C. ; Zhou, Zhanxiang ; Wang, Lipeng ; Song, Zhenyuan ; McClain, Craig J. ; Kang, Yujian. / Preservation of intestinal structural integrity by zinc is independent of metallothionein in alcohol-intoxicated mice. In: American Journal of Pathology. 2004 ; Vol. 164, No. 6. pp. 1959-1966.
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