Anti-Inflammatory and Cytoprotective Actions of Hydrogen Sulfide: Translation to Therapeutics

Abstract

Significance: There is a rapidly expanding body of evidence for important roles of hydrogen sulfide in protecting against tissue injury, reducing inflammation, and promoting repair. There is also growing evidence that H 2 S can be successfully exploited in drug development. Recent Advances: H 2 S synthesis and degradation are regulated in circumstances of inflammation and injury so as to promote repair and re-establish homeostasis. Novel H 2 S-releasing drugs exhibit enhanced anti-inflammatory and pro-restorative effects, while having reduced adverse effects in many tissues. Critical Issues: H 2 S is a pleiotropic mediator, having effects on many elements in the inflammatory cascade and promoting the resolution of inflammation and injury. It also contributes significantly to mucosal defence in the gastrointestinal tract, and in host defence against infection. There is strong evidence that novel, H 2 S-based therapeutics are safe and effective in animal models, and several are progressing through human trials. Future Directions: A better understanding of the physiological and pathophysiological roles of H 2 S continues to be restrained by the lack of simple, reliable methods for measurement of H 2 S synthesis, and the paucity of highly selective inhibitors of enzymes that participate in endogenous H 2 S synthesis. On the other hand, H 2 S donors show promise as therapeutics for several important indications. Antioxid. Redox Signal. 22, 398–410.