Resveratrol alleviates aluminum‐induced intestinal barrier dysfunction in mice

• DOI: 10.1002/tox.23490
• Publication Date: 2022-02-14T14:28:07Z
• Authors: Wudi Hao; Xiaoying Zhu; Ziyue Liu; Yushuai Song; Shengwen Wu; Xiaobo Lu; Jinghua Yang; Cuihong Jin
• Keywords: 0301 basic medicine; 0303 health sciences; Tight Junction Proteins; 3. Good health; Mice; 03 medical and health sciences; Matrix Metalloproteinase 9; Sirtuin 1; Resveratrol; Interferon Regulatory Factors; Animals; Cytokines; Humans; Intestinal Mucosa; Aluminum

AbstractBackgroundAluminum is mainly exposed to the general population through food and water, and is absorbed into the systemic circulation through intestine, which in turn damages the intestinal barrier.MethodsThe mice model of subchronic exposure to aluminum chloride (AlCl3) was established via oral. Tail suspension test was used to detect depressive behavior. H&E staining was performed to assess pathological intestinal injury. Intestinal permeability was estimated by exogenous Evans blue content. The level of inflammatory cytokines and tight junction protein were assessed via ELISA and western blotting. Simultaneously, resveratrol (Rsv, an agonist of Sirt1) was evaluated the protective role against intestinal barrier injuries caused by aluminum exposure.ResultsOur results showed that AlCl3 induced depressive‐like behavior, intestinal pathological damage and intestinal barrier permeability, resulting in intestinal barrier dysfunction. Besides, aluminum induced the expression of inflammatory cytokines, which further triggered IRF8‐MMP9‐mediated downregulation of tight junction proteins including CLD1, OCLD and ZO‐1. After Rsv treatment, SIRT1 expression was increased, depressive symptom was improved, pathological injury was reduced, inflammatory reaction was alleviated, and intestinal barrier function restored.ConclusionOur findings revealed that aluminum exposure induced intestinal barrier dysfunction by IRF8‐MMP9 signaling pathway. Rsv alleviated these injuries via activating SIRT1.