Hydrogen Sulfide Toxicity: Mechanism of Action, Clinical Presentation, and Countermeasure Development

Patrick C. Ng, Tara B. Hendry-Hofer, Alyssa E. Witeof, Matthew Brenner, Sari B. Mahon, Gerry R. Boss, Philippe Haouzi, Vikhyat S. Bebarta

Research output: Contribution to journalReview article

Abstract

Introduction: Hydrogen sulfide (H2S) is found in various settings. Reports of chemical suicide, where individuals have combined readily available household chemicals to produce lethal concentrations of H2S, have demonstrated that H2S is easily produced. Governmental agencies have warned of potential threats of use of H2S for a chemical attack, but currently there are no FDA-approved antidotes for H2S. An ideal antidote would be one that is effective in small volume, readily available, safe, and chemically stable. In this paper we performed a review of the available literature on the mechanism of toxicity, clinical presentation, and development of countermeasures for H2S toxicity. Discussion: In vivo, H2S undergoes an incomplete oxidation after an exposure. The remaining non-oxidized H2S is found in dissolved and combined forms. Dissolved forms such as H2S gas and sulfhydryl anion can diffuse between blood and tissue. The combined non-soluble forms are found as acid-labile sulfides and sulfhydrated proteins, which play a role in toxicity. Recent countermeasure development takes into account the toxicokinetics of H2S. Some countermeasures focus on binding free hydrogen sulfide (hydroxocobalamin, cobinamide); some have direct effects on the mitochondria (methylene blue), while others work by mitigating end organ damage by generating other substances such as nitric oxide (NaNO2). Conclusion: H2S exists in two main pools in vivo after exposure. While several countermeasures are being studied for H2S intoxication, a need exists for a small-volume, safe, highly effective antidote with a long shelf life to treat acute toxicity as well as prevent long-term effects of exposure.

Original languageEnglish (US)
Pages (from-to)287-294
Number of pages8
JournalJournal of Medical Toxicology
Volume15
Issue number4
DOIs
StatePublished - Oct 1 2019

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Antidotes
Hydrogen Sulfide
Toxicity
Hydroxocobalamin
Methylene Blue
Sulfides
Chemical attack
Suicide
Mitochondria
Anions
Nitric Oxide
Gases
Acids
Blood
Tissue
Oxidation
Proteins

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Ng, P. C., Hendry-Hofer, T. B., Witeof, A. E., Brenner, M., Mahon, S. B., Boss, G. R., ... Bebarta, V. S. (2019). Hydrogen Sulfide Toxicity: Mechanism of Action, Clinical Presentation, and Countermeasure Development. Journal of Medical Toxicology, 15(4), 287-294. https://doi.org/10.1007/s13181-019-00710-5
Ng, Patrick C. ; Hendry-Hofer, Tara B. ; Witeof, Alyssa E. ; Brenner, Matthew ; Mahon, Sari B. ; Boss, Gerry R. ; Haouzi, Philippe ; Bebarta, Vikhyat S. / Hydrogen Sulfide Toxicity : Mechanism of Action, Clinical Presentation, and Countermeasure Development. In: Journal of Medical Toxicology. 2019 ; Vol. 15, No. 4. pp. 287-294.
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Ng, PC, Hendry-Hofer, TB, Witeof, AE, Brenner, M, Mahon, SB, Boss, GR, Haouzi, P & Bebarta, VS 2019, 'Hydrogen Sulfide Toxicity: Mechanism of Action, Clinical Presentation, and Countermeasure Development', Journal of Medical Toxicology, vol. 15, no. 4, pp. 287-294. https://doi.org/10.1007/s13181-019-00710-5

Hydrogen Sulfide Toxicity : Mechanism of Action, Clinical Presentation, and Countermeasure Development. / Ng, Patrick C.; Hendry-Hofer, Tara B.; Witeof, Alyssa E.; Brenner, Matthew; Mahon, Sari B.; Boss, Gerry R.; Haouzi, Philippe; Bebarta, Vikhyat S.

In: Journal of Medical Toxicology, Vol. 15, No. 4, 01.10.2019, p. 287-294.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Hydrogen Sulfide Toxicity

T2 - Mechanism of Action, Clinical Presentation, and Countermeasure Development

AU - Ng, Patrick C.

AU - Hendry-Hofer, Tara B.

AU - Witeof, Alyssa E.

AU - Brenner, Matthew

AU - Mahon, Sari B.

AU - Boss, Gerry R.

AU - Haouzi, Philippe

AU - Bebarta, Vikhyat S.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Introduction: Hydrogen sulfide (H2S) is found in various settings. Reports of chemical suicide, where individuals have combined readily available household chemicals to produce lethal concentrations of H2S, have demonstrated that H2S is easily produced. Governmental agencies have warned of potential threats of use of H2S for a chemical attack, but currently there are no FDA-approved antidotes for H2S. An ideal antidote would be one that is effective in small volume, readily available, safe, and chemically stable. In this paper we performed a review of the available literature on the mechanism of toxicity, clinical presentation, and development of countermeasures for H2S toxicity. Discussion: In vivo, H2S undergoes an incomplete oxidation after an exposure. The remaining non-oxidized H2S is found in dissolved and combined forms. Dissolved forms such as H2S gas and sulfhydryl anion can diffuse between blood and tissue. The combined non-soluble forms are found as acid-labile sulfides and sulfhydrated proteins, which play a role in toxicity. Recent countermeasure development takes into account the toxicokinetics of H2S. Some countermeasures focus on binding free hydrogen sulfide (hydroxocobalamin, cobinamide); some have direct effects on the mitochondria (methylene blue), while others work by mitigating end organ damage by generating other substances such as nitric oxide (NaNO2). Conclusion: H2S exists in two main pools in vivo after exposure. While several countermeasures are being studied for H2S intoxication, a need exists for a small-volume, safe, highly effective antidote with a long shelf life to treat acute toxicity as well as prevent long-term effects of exposure.

AB - Introduction: Hydrogen sulfide (H2S) is found in various settings. Reports of chemical suicide, where individuals have combined readily available household chemicals to produce lethal concentrations of H2S, have demonstrated that H2S is easily produced. Governmental agencies have warned of potential threats of use of H2S for a chemical attack, but currently there are no FDA-approved antidotes for H2S. An ideal antidote would be one that is effective in small volume, readily available, safe, and chemically stable. In this paper we performed a review of the available literature on the mechanism of toxicity, clinical presentation, and development of countermeasures for H2S toxicity. Discussion: In vivo, H2S undergoes an incomplete oxidation after an exposure. The remaining non-oxidized H2S is found in dissolved and combined forms. Dissolved forms such as H2S gas and sulfhydryl anion can diffuse between blood and tissue. The combined non-soluble forms are found as acid-labile sulfides and sulfhydrated proteins, which play a role in toxicity. Recent countermeasure development takes into account the toxicokinetics of H2S. Some countermeasures focus on binding free hydrogen sulfide (hydroxocobalamin, cobinamide); some have direct effects on the mitochondria (methylene blue), while others work by mitigating end organ damage by generating other substances such as nitric oxide (NaNO2). Conclusion: H2S exists in two main pools in vivo after exposure. While several countermeasures are being studied for H2S intoxication, a need exists for a small-volume, safe, highly effective antidote with a long shelf life to treat acute toxicity as well as prevent long-term effects of exposure.

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