Synthesis and Biological Effects of Hydrogen Sulfide (H₂S): Development of H₂S-Releasing Drugs as Pharmaceuticals

Abstract

Gaseous transmitters are a growing family of regulatory\ud molecules involved in multilevel regulation of physiological\ud and pathological functions in mammalian tissues. Hydrogen\ud sulfide (H2S) is best known for its characteristic smell of\ud rotten eggs. It is now widely recognized that H2S, along with\ud nitric oxide (NO) and carbonmonoxide (CO), is involved in a\ud multitude of physiological functions. The generation of H2S\ud bymammalian tissues is likely to occur in a slow and constant\ud rate, and it appears to be involved in several processes including\ud neuromodulation, hypertension, inflammation, edema,\ud hemorrhagic shock, pain perception, gastric mucosal integrity,\ud and vascular tone.\ud This Perspective has been designed in order to give to the\ud reader an updated overview on the physiology and biochemistry\ud of H2S. In particular we have summarized the effects of\ud H2S inhibitors and H2S donors in animal models of disease\ud ordered for apparatus. Finally there is a section that addresses\ud the potential for therapeutic exploitation ofH2S and provides\ud an update on the patents so far filed

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

“…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).…”

“…Na 2 S and sodium hydrosulfide (NaHS) have been used as H 2 S donor compounds in the majority of experimental studies (2,3). However, because the half-lives of these sulfide salts are very short in biological fluid, plasma sulfide levels rapidly increase after bolus administration of Na 2 S or NaHS and then return to baseline instantaneously (5).…”

“…However, because the half-lives of these sulfide salts are very short in biological fluid, plasma sulfide levels rapidly increase after bolus administration of Na 2 S or NaHS and then return to baseline instantaneously (5). To sustain "physiological" levels of sulfide in circulation after bolus administration, many slow-releasing H 2 S donor compounds, including ACS48, have been developed (2,6).…”

BK Channels – Focus on Polyamines, Ethanol/Acetaldehyde and Hydrogen Sulfide (H2S)

“…H 2 S -similar to the other gasotransmitters NO or CO -is water and lipid soluble and therefore also easily passes membranes. The physiology, pathophysiology, pharmacology of H 2 S particularly in the vascular system and brain has been reviewed i n a n i m p r e s s i v e a m o u n t o f r e c e n t publications (Wang 2011;Kimura 2011;Hu et al, 2011;Bucci & Cirino 2011;Wang 2010;Tan et al 2010;Gadalla & Snyder 2010;Mustafa et al, 2009;Mancardi et al, 2009;Qu et al, 2008;Li & Moore 2008;Łowicka & Bełtowski 2007;Szabó 2007;Wallace 2007;Wallace 2010;Lloyd 2006;Wang 2002;Boehning and Snyder 2003;Caliendo et al, 2010). Besides many other cellular targets H 2 S also acts on ion channels.…”

Hydrogen sulfide inhibits IL-8 expression in human keratinocytes via MAP kinase signaling

“…20 It has been reported that the activity of the p38 and extracellular signalregulated kinase (ERK)1/2 MAPKs is increased in lesional psoriatic skin as compared with non-lesional skin. 21,22 Many studies have been published on the involvement of hydrogen sulfide in inflammation, and evidence has been shown for both pro-or anti-inflammatory roles of H 2 S. 23,24 Recently, we have demonstrated that hydrogen sulfide can impair human keratinocytes adhesion and proliferation by impairing the activation of Raf-MEK-ERK pathway. 22 The specific interest to hydrogen sulfide derives from the potential applications of the results, as sulfur is able to penetrate the skin and a sulfur-rich balneotherapy, known to be effective in the treatment of psoriasis, 25 might turn useful in this disease.…”