2026/01/06 by Ye Chen, Yulin Deng, Rong Tang +3 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Genomics, phytochemicals, and oxidative stress #Redox biology and oxidative stress #Sulfur Compounds in Biology
paper · doi:10.4103/mgr.medgasres-d-25-00100
openalex publication_date 2026/01/06 · openalex created_date 2026/01/08 · openalex updated_date 2026/07/25
Ischemia-reperfusion injury, a critical pathophysiological phenomenon in multiple organ systems, remains a formidable therapeutic challenge in clinical practice. As the third endogenously produced gaseous signaling molecule, hydrogen sulfide (H2S) has emerged as a pivotal regulator of diverse physiological processes and pathological cascades. Accumulating evidence indicates that H2S exerts cytoprotective effects against cerebral, cardiac, hepatic, renal, and pulmonary ischemia-reperfusion injuries through multifaceted mechanisms involving mitigation of inflammatory responses, suppression of oxidative stress, modulation of autophagic processes, and inhibition of apoptotic pathways. This comprehensive review systematically examines the endogenous biosynthesis and metabolic regulation of H2S, while elucidating the molecular mechanisms underlying its organ protective effects during ischemia-reperfusion injury. Particular emphasis is placed on the therapeutic potential of H2S synthase isoforms and bioactive metabolites in ischemic pathophysiology. Notably, recent advances in H2S pharmacology have catalyzed the development of novel H2S donors and slow-releasing compounds, including HSDF-NH2, S-allyl cysteine, S-propargyl cysteine, and S-(4-fluorobenzyl)-N-(3,4,5-trimethoxybenzoyl)-L-cysteine. These pharmacological innovations demonstrate enhanced tissue specificity and controlled release kinetics, paving the way for clinical translation of H2S-based therapeutics in ischemia-reperfusion injury management. Future research directions should focus on optimizing drug delivery systems and elucidating the spatiotemporal dynamics of H2S signaling in organ-specific ischemia-reperfusion pathologies.