Detection of hydrogen sulfide in biological samples: Current and future

Department of Pathology, LSU Health Sciences Center, Shreveport, LA 71130, USA.
Expert Review of Clinical Pharmacology (Impact Factor: 2.18). 01/2011; 4(1):9-12. DOI: 10.1586/ecp.10.132
Source: PubMed


Evaluation of: Levitt MD, Abdel-Rehim MS, Furne J. Free and acid-labile hydrogen sulfide concentrations in mouse tissues: anomalously high free hydrogen sulfide in aortic tissue. Antioxid. Redox Signal. DOI: 10.1089/ars.2010.3525 (2010) (Epub ahead of print). Hydrogen sulfide (H(2)S), known as a pungent toxic gas, has recently emerged as a novel critical mediator in the cardiovascular system, the nervous system and various biological signaling functions, as well as a therapeutic agent. However, much less certainty exists regarding biological levels of H(2)S in these systems and during disease. Many papers have reported various methods of measuring the levels of sulfide through different techniques both in vitro and in vivo. Complicating this matter is the fact that sulfide exists in multiple forms - free sulfides such as S(2) (-), HS(-), H(2)S, acid-labile and bound sulfides. These different forms of sulfide make quantitative measurement of bioavailable H(2)S difficult and have led to variable reported levels in the literature. The sensitive detection of sulfide in its multiple forms is needed to establish reliable bioavailable concentrations of sulfide species in order to understand their role in various aspects of physiology and pathology, and to address possible therapeutic approaches. A recent method by Levitt et al. describes a unique gas chromatography chemiluminescence-based technique to measure free and acid-labile H(2)S in multiple tissues from mouse.

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    ABSTRACT: Background: Owing to recent discoveries of many hydrogen sulfide-mediated physiological processes, sulfide biology is in the focus of scientific research. However, the promiscuous chemical properties of sulfide pose complications for biological studies, which led to accumulation of controversial observations in the literature. Scope of review: We intend to provide an overview of fundamental thermodynamic and kinetic features of sulfide redox- and coordination-chemical reactions and protonation equilibria in relation to its biological functions. In light of these chemical properties we review the strengths and limitations of the most commonly used sulfide detection methods and recently developed fluorescent probes. We also give a personal perspective on blood and tissue sulfide measurements based on proposed biomolecule-sulfide interactions and point out important chemical aspects of handling sulfide reagent solutions. Major conclusions: The diverse chemistries of sulfide detection methods resulted in orders of magnitude differences in measured physiological sulfide levels. Investigations that were aimed to dissect the underlying molecular reasons responsible for these controversies made the important recognition that there are large sulfide reserves in biological systems. These sulfide pools are tightly regulated in a dynamic manner and they are likely to play a major role in regulation of endogenous-sulfide-mediated biological functions and avoiding toxic side effects. General significance: Working with sulfide is challenging, because it requires considerable amounts of chemical knowledge to adequately handle reagent sulfide solutions and interpret biological observations. Therefore, we propose that a rigorous chemical approach could aid the reconciliation of the increasing number of controversies in sulfide biology. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.
    Full-text · Article · Jun 2013 · Biochimica et Biophysica Acta
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    ABSTRACT: Hydrogen sulfide is rapidly emerging as a key physiological mediator and potential therapeutic tool in numerous areas such as acute and chronic inflammation, neurodegenerative and cardiovascular disease, diabetes, obesity and cancer. However, the vast majority of the published studies have employed crude sulfide salts such as sodium hydrosulfide (NaSH) and sodium sulfide (Na2S) as H2S "donors" to generate H2S. Although these salts are cheap, readily available and easy to use, H2S generated from them occurs as an instantaneous and pH-dependent dissociation, whereas endogenous H2S synthesis from the enzymes cystathionine γ-lyase, cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase is a slow and sustained process. Furthermore, sulfide salts are frequently used at concentrations (e.g. 100 μM to 10 mM) far in excess of the levels of H2S reported in vivo (nM to low μM). For the therapeutic potential of H2S is to be properly harnessed, pharmacological agents which generate H2S in a physiological manner and deliver physiologically relevant concentrations are needed. The phosphorodithioate GYY4137 has been proposed as "slow-release" H2S donors and has shown promising efficacy in cellular and animal model diseases such as hypertension, sepsis, atherosclerosis, neonatal lung injury and cancer. However, H2S generation from GYY4137 is inefficient necessitating its use at high concentrations/doses. However, structural modification of the phosphorodithioate core has led to compounds (e.g. AP67 and AP105) with accelerated rates of H2S generation and enhanced biological activity. In this review, the therapeutic potential and limitations of GYY4137 and related phosphorodithioate derivatives are discussed.
    No preview · Article · Jul 2015 · Handbook of experimental pharmacology