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A New Aspect of Penehyclidine Hydrochloride in Alleviating Myocardial Ischemia–Reperfusion Injury: Ferroptosis

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Abstract

Penehyclidine hydrochloride (PHC) is an anticholinergic drug with cardioprotective effects. Ferroptosis is closely related to myocardial ischaemia-reperfusion injury (MIRI). In the present study, MIRI was induced in rats by left anterior descending coronary artery ligation. PHC pretreatment increased haemodynamic parameters and histopathological damage and reduced myocardial infarction size in the MIRI model. PHC pretreatment also inhibited ferroptosis, which was characterized by the decreased levels of Fe2+, 4-hydroxynonenal and ACSL4, and increased levels of GPX4, GSH-Px and GST. In response to 6 h of oxygen-glucose deprivation and 18 h of reoxygenation, PHC pretreatment had the same effects on these factors in H9c2 cells and reduced lipid ROS levels. Furthermore, ACSL4 overexpression reversed the protective effects of PHC on H9c2 cells. These results indicated that PHC inhibited MIRI through ACSL4-mediated ferroptosis. This study demonstrated that PHC could inhibit ferroptosis in MIRI and the relationship among PHC, ACSL4, ferroptosis and MIRI.

Graphical Abstract

This study demonstrated the inhibitory effect of PHC on ferroptosis and showed that PHC affects MIRI through ACSL4-mediated ferroptosis in vivo and in vitro.

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Data Availability

All data used for figures and results are available from the corresponding author on reasonable request.

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Acknowledgements

We are grateful for the support from the National Natural Science Foudation of China and the Capital Medical University.

Funding

This study was supported by the National Natural Science Foundation of China (under Grant 82172151).

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Authors and Affiliations

  1. Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, No. 2, Anzhen Road, Beijing, 100029, People’s Republic of China

    Duomao Lin, Boqun Cui, Zeyou Qi, Wenjun Liu & Guanzheng Zhang

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Contributions

Conception and methodology: Duomao Lin and Boqun Cui; Formal analysis: Zeyou Qi and Wenjun Liu; Supervision: Guanzheng Zhang. All authors edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Duomao Lin.

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Lin, D., Cui, B., Qi, Z. et al. A New Aspect of Penehyclidine Hydrochloride in Alleviating Myocardial Ischemia–Reperfusion Injury: Ferroptosis. J. of Cardiovasc. Trans. Res. 16, 1373–1382 (2023). https://doi.org/10.1007/s12265-023-10420-7

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