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

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.