The therapeutic potential of hydrogen sulfide: separating hype from hope

Abstract

Hydrogen sulfide (H2S) has become the hot new signaling molecule that seemingly affects all organ systems and biological processes in which it has been investigated. It has also been shown to have both proinflammatory and anti-inflammatory actions and proapoptotic and anti-apoptotic effects and has even been reported to induce a hypometabolic state (suspended animation) in a few vertebrates. The exuberance over potential clinical applications of natural and synthetic H2S-“donating” compounds is understandable and a number of these function-targeted drugs have been developed and show clinical promise. However, the concentration of H2S in tissues and blood, as well as the intrinsic factors that affect these levels, has not been resolved, and it is imperative to address these points to distinguish between the physiological, pharmacological, and toxicological effects of this molecule. This review will provide an overview of H2S metabolism, a summary of many of its reported “physiological” actions, and it will discuss the recent development of a number of H2S-donating drugs that show clinical potential. It will also examine some of the misconceptions of H2S chemistry that have appeared in the literature and attempt to realign the definition of “physiological” H2S concentrations upon which much of this exuberance has been established.

Hydrogen sulfide (H2S) and hypoxia inhibit salmonid gastrointestinal motility: evidence for H2S as an oxygen sensor

“…Recent studies have shown that exogenous hydrogen sulfide (H 2 S) initiates pharmacophysiological responses in most, if not all, organ systems (Li et al, 2011;Olson, 2011). These studies have been instrumental in the hypothesis that hydrogen sulfide is a biologically relevant signaling molecule thereby joining nitric oxide (NO) and carbon monoxide (CO) as 'gasotransmitters' (Wang, 2002).…”

A Novel Hydrogen Sulfide-releasing N-Methyl-d-Aspartate Receptor Antagonist Prevents Ischemic Neuronal Death

“…Hydrogen sulfide has been proposed as a gaseous signaling molecule along with nitric oxide and carbon monoxide (1). A number of studies suggested therapeutic potential of H 2 S-donating compounds and H 2 S gas itself for a number of animal models of human disease including ischemic brain injury (2,3).…”

“…Gaseous H 2 S, however, may be difficult to be used clinically because of its characteristic odor and toxicity at high concentrations (1,4). Na 2 S and sodium hydrosulfide (NaHS) have been used as H 2 S donor compounds in the majority of experimental studies (2,3).…”

“…The purity of the final product was greater than 98%. The structure of the final product was confirmed by mass spectrometry (Finnigan LCQ Advantage, ESIϩ) and 1 6 cells per dish) for measurements of intracellular calcium. Cell culture medium was replaced every 2 days, and the cultures were maintained at 37°C in 95% air/5% CO 2 in a humidified incubator.…”

Anoxia-Induced Suspended Animation in Caenorhabditis elegans

“…Hydrogen sulfide, or molecules with similar capabilities, provides a possible therapeutic approach to treating individuals with life-threatening events that compromise oxygen delivery to vital organs (Aslami et al, 2010;Szabo, 2007;Wagner et al, 2009). Like many new ideas that address biologically and medically complex problems, the ability to use basic sciences from model systems to identify treatments and therapeutics for the benefit of human health related issues is going to be costly, perhaps controversial and quite complex at the biological level (Olson, 2011). However, given the profound effect oxygen deprivation, including anoxia, has on living systems it is of great interest to continue the onward march toward understanding the molecular nature of anoxia tolerance in biological systems.…”