Journal Articles

Preventing Gut Leakiness and Endotoxemia Contributes to the Protective Effect of Zinc on Alcohol-Induced Steatohepatitis in Rats

October 14, 2015

Preventing Gut Leakiness and Endotoxemia Contributes to the Protective Effect of Zinc on Alcohol-Induced Steatohepatitis in Rats, J Nutr. 2015 Oct 14, Zhong W1, Li Q1, Sun Q2, Zhang W1, Zhang J3, Sun X1, Yin X3, Zhang X3, Zhou Z4.

  • 1Center for Translational Biomedical Research and.
  • 2Center for Translational Biomedical Research and Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC; and.
  • 3Department of Chemistry, University of Louisville, Louisville, KY.
  • 4Center for Translational Biomedical Research and Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC; and z_zhou@uncg.edu.

Abstract

BACKGROUND:

Zinc deficiency has been well documented in alcoholic liver disease.

OBJECTIVE:

This study was undertaken to determine whether dietary zinc supplementation provides beneficial effects in treating alcohol-inducedgut leakiness and endotoxemia.

METHODS:

Male Sprague Dawley rats were divided into 3 groups and pair-fed (PF) the Lieber-DeCarli liquid diets for 8 wk: 1) control (PF); 2) alcohol-fed (AF; 5.00-5.42% wt:vol ethanol); and 3) AF with zinc supplementation (AF/Zn) at 220 ppm zinc sulfate heptahydrate. The PF and AF/Zn groups were pair-fed to the AF group. Hepatic inflammation and endotoxin signaling were determined by immunofluorescence and quantitative polymerase chain reaction (qPCR). Alterations in intestinal tight junctions and aldehyde dehydrogenases were assessed by qPCR and Western blot.

RESULTS:

The AF rats had greater macrophage activation and cytokine production (P < 0.05) in the liver compared with the PF rats, whereas the AF/Zn rats showed no significant differences (P > 0.05). Plasma endotoxin levels of the AF rats were 136% greater than that of the PF rats, whereas the AF/Zn rats showed no difference with the PF rats. Ileal permeability was 255% greater in the AF rats and 19% greater in the AF/Zn rats than in the PF rats. The AF group reduced intestinal claudin-1, occludin, and zona occludens-1 (ZO-1) expression, and the AF/Zn group upregulated claudin-1 and ZO-1 expression (P < 0.05) compared with the PF group. The intestinal epithelial expression and activity of aldehyde dehydrogenases were elevated (P < 0.05) in the AF/Zn rats compared with that of the AF rats. Furthermore, the ileal expression and function of hepatocyte nuclear factor 4α, which was impaired in the AF group, was significantly elevated in the AF/Zn group compared with the PF group.

CONCLUSIONS:

The results demonstrate that attenuating hepatic endotoxin signaling by preserving the intestinal barrier contributes to theprotective effect of zinc on alcohol-induced steatohepatitis in rats.

© 2015 American Society for Nutrition.

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