Sulfur Dioxide: Endogenous Generation, Biological Effects, Detection, and Therapeutic Potential

Significance: Previously, sulfur dioxide (SO₂) was recognized as an air pollutant. However, it is found to be endogenously produced in mammalian tissues. As a new gasotransmitter, SO₂ is involved in regulating the structure and function of blood vessels, heart, lung, gastrointestinal tract, nervous system, etc.Recent Advances: Increasing evidence showed that endogenous SO₂ regulates cardiovascular physiological processes, such as blood pressure control, vasodilation, maintenance of the normal vascular structure, and cardiac negative inotropy. Under pathological conditions including hypertension, atherosclerosis, vascular calcification, aging endothelial dysfunction, myocardial injury, myocardial hypertrophy, diabetic myocardial fibrosis, sepsis-induced cardiac dysfunction, pulmonary hypertension, acute lung injury, colitis, epilepsy-related brain injury, depression and anxiety, and addictive drug reward memory consolidation, endogenous SO₂ protects against the pathological changes via different molecular mechanisms and the disturbed SO₂/aspartate aminotransferase pathway is likely involved in the mechanisms for the earlier mentioned pathologic processes. Critical Issues: A comprehensive understanding of the biological effects of endogenous SO₂ is extremely important for the development of novel SO₂ therapy. In this review, we summarized the biological effects, mechanism of action, SO₂ detection methods, and its related prodrugs. Future Directions: Further studies should be conducted to understand the effects of endogenous SO₂ in various physiological and pathophysiological processes and clarify its underlying mechanisms. More efficient and accurate SO₂ detection methods, as well as specific and effective SO₂-releasing systems should be designed for the treatment and prevention of clinical related diseases. The translation from SO₂ basic medical research to its clinical application is also worthy of further study. Antioxid. Redox Signal. 36, 256-274.