A Practical Look at the Chemistry and Biology of Hydrogen Sulfide

Olson, Kenneth R.

doi:10.1089/ars.2011.4401

Cited by 186 publications

(185 citation statements)

References 79 publications

(94 reference statements)

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“…We also found that CMBBH 2 S increased sharply, with a very steep slope, when the rate of H 2 S administration was close to the lethal levels of exposure, corresponding to a CMBBH 2 S around 30 -40 M. Wintner et al (54) also showed, using a series of in vitro studies, that the MBB technique can identify H 2 S present in various forms in the blood. First, H 2 S concentrations in the plasma were similar to the values obtained using amperometry, which only measures soluble H 2 S (15,30,37). We found that in saline, CMBBH 2 S did not change within 10 min, if evaporation of H 2 S was prevented, in keeping with our previous results (49,50).…”

Section: What Was Measured In the Blood?supporting

confidence: 89%

H₂S concentrations in the arterial blood during H₂S administration in relation to its toxicity and effects on breathing

Klingerman

Trushin

Prokopczyk

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

129

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Klingerman CM, Trushin N, Prokopczyk B, Haouzi P. H2S concentrations in the arterial blood during H2S administration in relation to its toxicity and effects on breathing. Am J Physiol Regul Integr Comp Physiol 305: R630 -R638, 2013. First published July 31, 2013; doi:10.1152/ajpregu.00218.2013.-Our aim was to establish in spontaneously breathing urethane-anesthetized rats, the relationship between the concentrations of H2S transported in the blood and the corresponding clinical manifestations, i.e., breathing stimulation and inhibition, during and following infusion of NaHS at increasing rates. The gaseous concentration of H2S (CgH2S, one-third of the total soluble form) was computed from the continuous determination of H2S partial pressure in the alveolar gas, while H2S, both dissolved and combined to hemoglobin, was measured at specific time points by sulfide complexation with monobromobimane (CMBBH2S). We found that using a potent reducing agent in vitro, H 2S added to the whole blood had little interaction with the plasma proteins, as sulfide appeared to be primarily combined and then oxidized by hemoglobin. In vivo, H 2S was undetectable in the blood in its soluble form in baseline conditions, while CMBBH 2S averaged 0.7 Ϯ 0.5 M. During NaHS infusion, H 2S was primarily present in nonsoluble form in the arterial blood: CMBBH 2S was about 50 times higher than CgH 2S at the lowest levels of exposure and 5 or 6 times at the levels wherein fatal apnea occurred. CgH 2S averaged only 1.1 Ϯ 0.7 M when breathing increased, corresponding to a CMBBH 2S of 11.1 Ϯ 5.4 M. Apnea occurred at CgH 2S above 5.1 M and CMBBH2S above 25.4 M. At the cessation of exposure, CMBBH 2S remained elevated, at about 3 times above baseline for at least 15 min. These data provide a frame of reference for studying the putative effects of endogenous H 2S and for testing antidotes against its deadly effects.

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Section: What Was Measured In the Blood?supporting

confidence: 89%

H₂S concentrations in the arterial blood during H₂S administration in relation to its toxicity and effects on breathing

Klingerman

Trushin

Prokopczyk

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

129

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“…Low concentrations of H 2 S irritate the eyes, nose, throat, and respiratory system; high concentrations of H 2 S lead to rapid loss of consciousness and death (Evans 1967;Li and Lancaster 2013;Lindenmann et al 2010). Interestingly, this gaseous molecule has been recently classified as a member of the gasotransmitter family, sharing similarities with its congeners nitric oxide (NO), carbon monoxide (CO), and dioxygen (O 2 ) (Vandiver and Snyder 2012;Wang 2012;Li and Moore 2011;Szab o 2007;Kolluru et al 2013;Fukuto et al 2012;Olson et al 2012;Olson 2012). The biosynthesis of H 2 S in mammalian tissues has been attributed to enzymes, including cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfur-transferase (3-MST), in combination with cysteine amino transferase (CAT) (Scheme 1) (King 2013;Martelli et al 2012a;Szabo 2012;Paul and Snyder 2012;Hu et al 2011;Prabhakar 2012).…”

Section: Introductionmentioning

confidence: 99%

Medicinal Chemistry: Insights into the Development of Novel H2S Donors

Zhao

Pacheco

Xian

2015

Handbook of Experimental Pharmacology

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Hydrogen sulfide (H2S) was traditionally considered as a toxic gas. However, recent studies have demonstrated H2S is an endogenously generated gaseous signaling molecule (gasotransmitter) with importance on par with that of two other well-known endogenous gasotransmitters, nitric oxide (NO) and carbon monoxide (CO). Although H2S's exact mechanisms of action are still under investigation, the production of endogenous H2S and the exogenous administration of H2S have been demonstrated to elicit a wide range of physiological responses including modulation of blood pressure and protection of ischemia reperfusion injury, exertion of anti-inflammatory effects, and reduction of metabolic rate. These results strongly suggest that modulation of H2S levels could have potential therapeutic values. In this regard, synthetic H2S-releasing agents (i.e., H2S donors) are not only important research tools, but also potential therapeutic agents. This chapter summarizes the knowledge of currently available H2S donors. Their preparation, H2S releasing mechanisms, and biological applications are discussed.

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“…15 The importance of thiol ionization in governing the reactivity via sulfenation followed by reductive polysulfide-forming reactions is illustrated by the fact that increasing the pH from 6 to 8 (ie, the physiological range) increases the oxidation rate of H 2 S 10-fold. 12,19 Although the formation of polysulfides from the reaction of H 2 S with oxygen or H 2 O 2 has been rationalized above in terms of a sulfenic acid intermediate, we have provided no evidence of this mechanism and so alternatives remain possible. As the chelator DTPA did not alter the reaction of H 2 S with oxygen or H 2 O 2 , it is perhaps reasonable to exclude a major role for transition metal impurities, such as iron participating in the oxygen or peroxide-mediated conversion of H 2 S into polysulfides.…”

Section: 18mentioning

confidence: 76%

“…11,12 Such deprotonated thiols can rapidly react with oxidants to form disulfide or polysulfide species, likely via a transient sulfenic acid intermediate. 13 These oxidized variants of H 2 S instead of being reducing agents in fact have oxidant properties that are anticipated to catalyze thiol oxidation via thioldisulfide exchange reactions.…”

Section: Stubbert Et Al H 2 S Via Polysulfides Oxidatively Activates mentioning

confidence: 99%

Protein Kinase G Iα Oxidation Paradoxically Underlies Blood Pressure Lowering by the Reductant Hydrogen Sulfide

et al. 2014

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Abstract-Dysregulated blood pressure control leading to hypertension is prevalent and is a risk factor for several common diseases. Fully understanding blood pressure regulation offers the possibility of developing rationale therapies to alleviate hypertension and associated disease risks. Although hydrogen sulfide (H 2 S) is a well-established endogenous vasodilator, the molecular basis of its blood-pressure lowering action is incompletely understood. H 2 S-dependent vasodilation and blood pressure lowering in vivo was mediated by it catalyzing formation of an activating interprotein disulfide within protein kinase G (PKG) Iα. However, this oxidative activation of PKG Iα is counterintuitive because H 2 S is a thiol-reducing molecule that breaks disulfides, and so it is not generally anticipated to induce their formation. This apparent paradox was explained by H 2 S in the presence of molecular oxygen or hydrogen peroxide rapidly converting to polysulfides, which have oxidant properties that in turn activate PKG by inducing the disulfide. These observations are relevant in vivo because transgenic knockin mice in which the cysteine 42 redox sensor within PKG has been systemically replaced with a redox-dead serine residue are resistant to H 2 S-induced blood pressure lowering. Thus, a primary mechanism by which the reductant molecule H 2 S lowers blood pressure is mediated somewhat paradoxically by the oxidative activation of PKG. (Hypertension. 2014;64:1344-1351.)

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A Practical Look at the Chemistry and Biology of Hydrogen Sulfide

Cited by 186 publications

References 79 publications

H₂S concentrations in the arterial blood during H₂S administration in relation to its toxicity and effects on breathing

H₂S concentrations in the arterial blood during H₂S administration in relation to its toxicity and effects on breathing

Medicinal Chemistry: Insights into the Development of Novel H2S Donors

Protein Kinase G Iα Oxidation Paradoxically Underlies Blood Pressure Lowering by the Reductant Hydrogen Sulfide

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