AUTHOR=Chen Hao , Tang Yutao , Ren Pan , Wu Wenbin 

TITLE=The unmet promise: a critical review of antioxidant strategies in myocardial ischemia-reperfusion injury and the path towards precision medicine

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1693441

DOI=10.3389/fphar.2025.1693441

ISSN=1663-9812

ABSTRACT=Myocardial ischemia-reperfusion injury (MIRI) remains a major clinical challenge, with oxidative stress as a key driver. Despite extensive preclinical promise, antioxidant therapies have consistently failed in clinical translation. This critical review deconstructs this translational gap, which stems from the nuanced complexity of redox biology, inappropriate therapeutic timing, and patient heterogeneity. We argue that overcoming these hurdles requires a paradigm shift from broad antioxidant supplementation to precision medicine. This approach involves enhancing endogenous defense mechanisms, leveraging targeted drug delivery, and developing multi-modal strategies. Ultimately, integrating dynamic biomarkers, multi-omics, and artificial intelligence to tailor treatments to individual patient profiles holds the key to finally fulfilling the promise of effectively managing MIRI.