Ferroptosis in heatstroke: Mechanisms and therapeutic perspectives (Review)

Abstract

Heatstroke is a life-threatening condition characterized by hyperthermia and systemic inflammatory response, often leading to multi-organ dysfunction and high mortality. Despite advances in understanding its pathophysiology, effective targeted therapies remain limited. Recent studies have highlighted ferroptosis, an iron-dependent, lipid peroxidation-driven form of regulated cell death, as a critical mechanism in heatstroke-induced organ injury. This review synthesizes current evidence on the role of ferroptosis in heatstroke, including key signaling pathways such as Hippo-Yes-associated protein-acyl-CoA synthetase long-chain family member 4, dysregulated heat shock response, and antioxidant defense failure. The present study also explored potential ferroptosis-related biomarkers and therapeutic strategies targeting this cell death pathway. Understanding ferroptosis in heatstroke not only unveils novel pathophysiological insights but also opens avenues for early diagnosis and targeted intervention.