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Open Access 22-04-2024 | Diabetes | Research

N-acetylcysteine Protects Against Myocardial Ischemia–Reperfusion Injury Through Anti-ferroptosis in Type 1 Diabetic Mice

Authors: Dongcheng Zhou, Yuhui Yang, Jiajia Chen, Jiaqi Zhou, Jianfeng He, Danyong Liu, Anyuan Zhang, Bixian Yuan, Yuxin Jiang, Weiyi Xia, Ronghui Han, Zhengyuan Xia

Published in: Cardiovascular Toxicology | Issue 5/2024

Abstract

The hearts of subjects with diabetes are vulnerable to ischemia–reperfusion injury (IRI). In contrast, experimentally rodent hearts have been shown to be more resistant to IRI at the very early stages of diabetes induction than the heart of the non-diabetic control mice, and the mechanism is largely unclear. Ferroptosis has recently been shown to play an important role in myocardial IRI including that in diabetes, while the specific mechanisms are still unclear. Non-diabetic control (NC) and streptozotocin-induced diabetic (DM) mice were treated with the antioxidant N-acetylcysteine (NAC) in drinking water for 4 week starting at 1 week after diabetes induction. Mice were subjected to myocardial IRI induced by occluding the coronary artery for 30 min followed by 2 h of reperfusion, subsequently at 1, 2, and 5 week of diabetes induction. The post-ischemic myocardial infarct size in the DM mice was smaller than that in NC mice at 1 week of diabetes but greater than that in the NC mice at 2 and 5 week of diabetes, which were associated with a significant increase of ferroptosis at 2 and 5 week but a significant reduction of ferroptosis at 1 week of diabetes. NAC significantly attenuated post-ischemic ferroptosis as well as oxidative stress and reduced infarct size at 2 and 5 week of diabetes. Application of erastin, a ferroptosis inducer, reversed the cardioprotective effects of NAC. It is concluded that increased oxidative stress and ferroptosis are the major factors attributable to the increased vulnerability to myocardial IRI in diabetes and that attenuation of ferroptosis represents a major mechanism whereby NAC confers cardioprotection against myocardial IRI in diabetes.

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Title: N-acetylcysteine Protects Against Myocardial Ischemia–Reperfusion Injury Through Anti-ferroptosis in Type 1 Diabetic Mice
Authors: Dongcheng Zhou
Yuhui Yang
Jiajia Chen
Jiaqi Zhou
Jianfeng He
Danyong Liu
Anyuan Zhang
Bixian Yuan
Yuxin Jiang
Weiyi Xia
Ronghui Han
Zhengyuan Xia
Publication date: 22-04-2024
Publisher: Springer US
Keywords: Diabetes
Acetylcysteine
Published in: Cardiovascular Toxicology / Issue 5/2024
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-024-09852-7

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