Resveratrol alleviates aluminum‐induced intestinal barrier dysfunction in mice

• Published in: Environmental toxicology Vol. 37; no. 6; pp. 1373 - 1381
• Main Authors: Hao, Wudi, Zhu, Xiaoying, Liu, Ziyue, Song, Yushuai, Wu, Shengwen, Lu, Xiaobo, Yang, Jinghua, Jin, Cuihong
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.06.2022; Wiley Subscription Services, Inc
• Subjects: Aluminium; Aluminum; Aluminum - toxicity; Aluminum chloride; aluminum exposure; Animals; Cytokines; Cytokines - metabolism; Damage; ELISA; Exposure; Gelatinase B; Humans; Inflammation; inflammatory factors; Injuries; Injury prevention; Interferon Regulatory Factors - metabolism; intestinal barrier dysfunction; Intestinal Mucosa - metabolism; Intestine; Intestines; Matrix Metalloproteinase 9 - metabolism; Mice; Permeability; Proteins; Resveratrol; Resveratrol - pharmacology; Signal transduction; SIRT1 protein; Sirtuin 1 - metabolism; Tight Junction Proteins; Water circulation; Western blotting; intestinal barrier dysfunction; aluminum exposure; inflammatory factors; resveratrol
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23490

Background Aluminum 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. Methods The 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. Results Our 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. Conclusion Our findings revealed that aluminum exposure induced intestinal barrier dysfunction by IRF8‐MMP9 signaling pathway. Rsv alleviated these injuries via activating SIRT1.