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Resveratrol Protects Oxidative Stress-Induced Intestinal Epithelial Barrier Dysfunction by Upregulating Heme Oxygenase-1 Expression

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Abstract

Background/Aim

Obstructive jaundice (OJ) is frequently complicated by infections and has been associated with increased bacterial translocation, intestinal epithelial hyperpermeability, and oxidative stress, but the mechanism remains unclear. The potential effect of resveratrol (Res) on modifying intestinal epithelial dysfunction was evaluated both in vitro and in vivo.

Methods

Caco-2 cells (in vitro) and male Wistar rats (n = 60; in vivo) were used to evaluate the role of Res on intestinal epithelial dysfunction. Hydrogen peroxide was used to induce oxidative stress in the Caco-2 cells. In bile duct-ligated group, OJ was successfully established on Day 7 after bile duct ligation, whereas sham-operated and vehicle-treated rats served as controls. Western blot and RT-qPCR were performed to analyze TJ proteins expression in epithelium isolated from rat intestine.

Results

Intestinal hyperpermeability was associated with decreased expression and phosphorylation of occludin and zonula occluden (ZO-1), but increased oxidation in Caco-2 cells and the intestinal epithelium. Res treatment increased the epithelial expression and phosphorylation of occludin and ZO-1 in a concentration-dependent manner. Moreover, Res which protected Caco-2 cells from H2O2-induced oxidative damage clearly reduced malondialdehyde level and intracellular reactive oxygen species accumulation, but increased the expression levels of superoxide dismutase and heme oxygenase-1 (HO-1). Further studies showed that Res also inhibited H2O2-induced protein kinase C activity and p38 phosphorylation. Interestingly, these effects of Res were abolished by the HO-1 inhibitor zinc protoporphyrin or knockdown of HO-1 by siRNA.

Conclusions

Res protected gut barrier function possibly by initiating HO-1-dependent signaling which is essential for common expression of key tight junction proteins. It also provides a rationale to develop Res clinical applications of intestinal disorders.

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Acknowledgments

This work was supported in part by a grant from the National Natural Science Foundation of China (No. 81170411) and the Health Department Foundation of Hebei Province, China (No. H2014206177).

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Authors and Affiliations

  1. Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Medical University, Hebei Institute of Gastroenterology, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei, China

    Na Wang, Qing Han, Gai Wang, Wei-Ping Ma, Jia Wang, Yu Guo, Li Liu, Xiao-Li Xie & Hui-Qing Jiang

  2. Pediatric Intensive Care Unit, Baoding Children’s Hospital, Baoding, Hebei, China

    Gai Wang

  3. Department of Pathology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

    Wen-Xin Wu

  4. Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, USA

    Xiao-Yu Jiang

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  1. Na Wang
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Wang, N., Han, Q., Wang, G. et al. Resveratrol Protects Oxidative Stress-Induced Intestinal Epithelial Barrier Dysfunction by Upregulating Heme Oxygenase-1 Expression. Dig Dis Sci 61, 2522–2534 (2016). https://doi.org/10.1007/s10620-016-4184-4

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