To the Editor,
We read with great interest the recent article by Brenner et al. on the use of a vitamin B12 analog, cobinamide, as a potential new antidote for hydrogen sulfide poisoning.Citation1 In this study, the use of spectroscopy for monitoring changes in oxy- and deoxyhemoglobin concentrations is quite elegant. Interestingly, it depicts a drop in oxyhemoglobin after 15 s of sodium hydrosulfide (NaHS) infusion, contrary to what would be expected in the setting of hydrogen- sulfide-induced inhibition of oxidative phosphorylation. That is, a fall in deoxyhemoglobin and rise in oxyhemoglobin are expected with prolonged exposure to hydrogen sulfide due to inhibition of cytochrome c oxidase and the predominance of anaerobic metabolism. This, in turn, results in impaired oxygen extraction from circulating blood. Could it be that we do not understand the mechanism by which the aqueous form of hydrogen sulfide causes toxicity, or is spectroscopy not a reliable tool?
The toxin used in this experiment is NaHS, a liquid formulation. However, toxicity due to hydrogen sulfide usually results from inhaling it in its gaseous phase, in which it acts as a cytochrome c oxidase inhibitor. Thereby, through this mechanism it uncouples oxidative phosphorylation, leading to cellular asphyxia as a result of the cell's decreased ability to extract oxygen from blood.Citation2–4 It is unclear whether the cellular effects of exposure to intravenous sodium hydrosulfide mimic those of exposure to hydrogen sulfide by inhalation. Others have shown a difference in the clinical effects of intravenous and inhaled hydrogen sulfide, and note that “the edematogenic effect of hydrogen sulfide in the lungs cannot be reproduced by injection of sodium hydrosulfide.”Citation5 Furthermore, from a modeling perspective, individuals exposed to hydrogen sulfide are typically removed from the source of exposure as the initial step in treatment of this toxicity; therefore, the clinical relevance of a continuous infusion model is unclear.
There is an inconsistency between the results described for dinitrocobinamide in Table 1 and Figure 3. In Figure 3, the curve illustrates the first mortality to be occurring at over 150 mg, whereas in Table 1, the same compound is described as causing the first mortality at 87 mg NaHS. A revision of this figure may clarify the results.
Taken together, the issues highlighted above may be useful to explore and clarify when planning future studies on the use of cobinamide as a treatment for hydrogen sulfide toxicity.
Declaration of interest
The authors report no declarations of interest. The authors alone are responsible for the content and writing of this letter.
References
- Brenner M, Benavides S, Mahon SB, Lee J, Yoon D, Mukai D, et al. The Vitamin B12 analog cobinamide is an effective hydrogen sulfide antidote in a lethal rabbit model. Clin Toxicol 2014; 52:490–497.
- Lindenmann J, Matzi V, Neuboeck N, Ratzenhofer-Komenda B, Maier A, Smolle-Juettner FM. Severe hydrogen sulphide poisoning treated with 4-dimethylaminophenol and hyperbaric oxygen. Diving Hyperb Med 2010; 8:213–217.
- Lewis RJ, Schnatter AR, Drummond I, Murray N, Thompson FS, Katz AM, et al. Mortality and cancer morbidity in a cohort of Canadian petroleum workers. Occup Environ Med 2003; 8:918–928.
- Schivanthan MC, Perera H, Jayasinghe S, Karunanayake P, Chang T, Ruwanpathirana S, et al. Hydrogen sulphide inhalational toxicity at a petroleum refinery in Sri Lanka: a case series of seven survivors following an industrial accident and a brief review of medical literature. Occup Environ Med 2013;8:9.
- Lopez A, Prior MG, Reifenstein RJ, Goodwin LR. Peracute toxic effects of inhaled hydrogen sulfide and injected sodium hydrosulfide on the lungs of rats. Fundam Appl Toxicol 1989;12:367–373.