Search

The past two decades have seen an upsurge in interest in the biology of naturally occurring gases, starting with nitric oxide and extending through to carbon monoxide. The latest addition to the list of biologically relevant gases is hydrogen sulfide. In the past few years, hydrogen sulfide has transited rapidly from environmental pollutant to biologically relevant mediator with potential roles in several physiological processes and disease states. Further, interest is now being shown in developing drugs which either mimic its effects or block its biosynthesis. Similarly to its gaseous cousins, the biology of hydrogen sulfide is proving to be complex and difficult to unravel.

Non-steroidal anti-inflammatory drugs are among the most commonly used drugs. Despite efforts to produce non-steroidal anti-inflammatory drugs that do not cause gastrointestinal ulceration and bleeding, these adverse effects remain major limitations to their use. In recent years, physiological roles of hydrogen sulfide ([H.sub.2]S) have been recognized, and there is emerging evidence that this endogenous gaseous substance can modulate inflammatory processes. Indeed, [H.sub.2]S donors have been shown to reduce edema formation and leukocyte adherence to the vascular endothelium, and to inhibit pro-inflammatory cytokine synthesis. Moreover, [H.sub.2]S donors can increase the resistance of the gastric mucosa to injury and accelerate repair. Taken together, these observations and others suggest that anti-inflammatory drugs that are modified to release [H.sub.2]S will exhibit improved efficacy and reduced toxicity. Such compounds have now been synthesized and shown to be markedly improved in many respects over the parent anti-inflammatory drugs.