Potential role of AhR in ischemia‑reperfusion injury and cancers: Focus on ferroptosis and lipid peroxidation signaling pathways (Review).

Abstract

The aryl hydrocarbon receptor (AhR) is a pivotal ligand‑activated transcription factor that plays a crucial role in maintaining cellular redox homeostasis. The disruption of redox homeostasis in the etiology of numerous diseases primarily manifests as the accumulation of reactive species and the attenuation of the antioxidant defenses, leading to the progressive buildup of lipid peroxides. This phenomenon significantly contributes to the initiation and progression of diseases, such as atherosclerosis, cancer, diabetes and ischemia‑reperfusion injury. Ferroptosis is a form of cell death characterized by iron dependency and lipid peroxidation. The regulation of ferroptosis presents a promising therapeutic target for anticancer therapy and the prevention of neurodegenerative and cardiovascular diseases. AhR transcriptionally regulates downstream target genes, thereby modulating the biosynthesis and accumulation of bioactive compounds and the antioxidant defense mechanism. This process is intricately linked to lipid peroxide accumulation and subsequent ferroptosis. The present review provides an overview of the influence of AhR on lipid peroxidation and ferroptosis, the potential therapeutic targets, and the prospective application value of targeting the AhR to influence lipid peroxidation‑ferroptosis processes in tumor cells and ischemia‑reperfusion injury.