Cheng MZ, Luo JH, Li X, Liu FY, Zhou WJ. Zinc pretreatment for protection against intestinal ischemia-reperfusion injury. World J Gastrointest Surg 2024; 16(12): 3843-3856 [DOI: 10.4240/wjgs.v16.i12.3843]
Corresponding Author of This Article
Wei-Jie Zhou, PhD, Professor, State Key Laboratory of Organ Failure Research, Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Road, Guangzhou 510515, Guangdong Province, China. weijiezhouum@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Ming-Zhen Cheng, Jia-Hao Luo, Wei-Jie Zhou, State Key Laboratory of Organ Failure Research, Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Xin Li, Department of Interventional Radiology, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100071, China
Feng-Yong Liu, Department of Interventional Radiology, Senior Department of Oncology, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100071, China
Co-first authors: Ming-Zhen Cheng and Jia-Hao Luo.
Co-corresponding authors: Feng-Yong Liu and Wei-Jie Zhou.
Author contributions: Cheng MZ and Luo JH contribute equally to this study as co-first authors. Liu FY and Zhou WJ contribute equally to this study as co-corresponding authors. Zhou WJ and Liu FY conceptualized the study; Cheng MZ, Luo JH and LX performed the experiments, the formal analysis, and the validation investigations; Cheng MZ collected the data; Zhou WJ and Liu FY wrote the original drafts; Zhou WJ wrote, reviewed and edited the manuscript; all authors have read and approved the final manuscript.
Institutional animal care and use committee statement: Animal-related research protocols were consistent with the United States Public Health Service Policy on the Use of Laboratory Animals and were approved by the Ethics Committee on the Use and Care of Animals of Southern Medical University.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data and materials used in this study are available from Zhou WJ (weijiezhouum@163.com) upon reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei-Jie Zhou, PhD, Professor, State Key Laboratory of Organ Failure Research, Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Road, Guangzhou 510515, Guangdong Province, China. weijiezhouum@163.com
Received: August 26, 2024 Revised: October 1, 2024 Accepted: October 28, 2024 Published online: December 27, 2024 Processing time: 92 Days and 23.2 Hours
Abstract
BACKGROUND
Intestinal ischemia-reperfusion (I/R) injury (II/RI) is a critical condition that results in oxidative stress, inflammation, and damage to multiple organs. Zinc, an essential trace element, offers protective benefits in several tissues during I/R injury, but its effects on intestinal II/RI remain unclear.
AIM
To investigate the effects of zinc pretreatment on II/RI and associated multiorgan damage.
METHODS
C57BL/6 mice were pretreated with zinc sulfate (ZnSO4, 10 mg/kg) daily for three days before I/R injury was induced via superior mesenteric artery occlusion (SMAO) and abdominal aortic occlusion (AAO) models. Tissue and serum samples were collected to evaluate intestinal, liver, and kidney damage using Chiu’s score, Suzuki score, and histopathological analysis. Caco-2 cells and intestinal organoids were used for in vitro hypoxia-reoxygenation injury models to measure reactive oxygen species (ROS) and superoxide dismutase (SOD) levels.
RESULTS
Zinc pretreatment significantly reduced intestinal damage in the SMAO and AAO models (P < 0.001). The serum levels of liver enzymes (alanine aminotransferase, aspartate aminotransferase) and kidney markers (creatinine and urea) were lower in the zinc-treated mice than in the control mice, indicating reduced hepatic and renal injury. In vitro, zinc decreased ROS levels and increased SOD activity in Caco-2 cells subject to hypoxia-reoxygenation injury. Intestinal organoids pretreated with zinc exhibited enhanced resilience to hypoxic injury compared to controls.
CONCLUSION
Zinc pretreatment mitigates II/RI and reduces associated multiorgan damage. These findings suggest that zinc has potential clinical applications in protecting against I/R injuries.
Core Tip: This study demonstrated the protective effects of zinc pretreatment on reducing oxidative stress, apoptosis, and multiorgan damage during intestinal ischemia-reperfusion injury (II/RI). Using mouse models and in vitro systems, zinc significantly mitigated damage in the intestine, liver, and kidneys by reducing reactive oxygen species production and enhancing cellular resilience to hypoxic injury. These findings highlight the potential clinical applications of zinc in protecting against II/RI and improving outcomes in patients experiencing ischemic events.
