Hydrogen sulphide: mechanism of toxic action, clinical manifestations of acute poisoning, pathohistological signs and treatment strategy

  • Authors: M.G. Prodanchuk, G.M. Balan, P.G. Zhminko, A.M. Stroy
  • UDC: 615.9: 546.221.1.
  • DOI: 10.33273/2663-4570-2024-97-2-54-72
Download attachments:

L.I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise), Kyiv, Ukraine

 

ABSTRACT. Hydrogen sulphide (H2S) is a highly toxic gas. Among this group of poisonous substances – causes of death – it is second only to carbon monoxide. The mechanism of its toxicity has not been sufficiently studied and there is currently no specific antidote therapy. This gas is a high-priority chemical threat in industry, as well as a potential terrorist weapon of mass destruction, especially in wartime.
Aim. Based on literary data and own researches, to summarize the current concepts of its toxicity mechanisms, clinical manifestations, treatment strategies and pathohistological signs of acute hydrogen sulphide poisoning.
Materials and Мethods. Open sources of public information and scientific literature on the research topic were analysed. An analytical review of the publications of scientific online libraries PubMed, Medline, Elsevier was carried out. A retrospective analysis of the
medical documentation of two cases with acute poisoning with H2S in combination with other toxic gases was carried out. The first case of acute poisoning with H2S and other sewage gases is in a patient who died in the conditions of a medical institution in the Kyiv region, who fell ill after a 15-minute stay in a household sewage septic tank. In the victim, the data of sectional and microscopic studies of lung tissue were also studied. The second case of acute H2S poisoning in combination with other gases of putrefaction is represented by three victims hospitalized at the clinic of the Research Centre of Preventive Toxicology, Food and Chemical Safety named after L.I. Medved, Ministry of Healthcare of Ukraine after cleaning a deep tank with the remains of rotten sauerkraut. One of the victims died after 6 hours. The methods of system comparative and content analysis were applied.
Results. Modern ideas about the mechanism of the toxic effect of H2S indicate that it is a rapidly metabolizing systemic toxicant that affects mitochondria, is the basis for the formation of tissue hypoxia, activation of oxidative stress, inflammatory reactions, and apoptosis. Under the acute effects of H2S, the main target organs are the nervous, bronchopulmonary and cardiovascular systems. Until now, there are no specific antidotes for the treatment of H2S poisoning, so it includes oxygen, symptomatic and supportive therapy. New therapeutic agents – potential antidotes are at the stage of preclinical research, most of which are aimed at binding H2S. There is an urgent need for the development of new therapeutic agents – absorbents (scavengers) of H2S for the prevention and treatment of poisoning, reducing morbidity and mortality.
Keywords: hydrogen sulphide, toxicity, acute poisoning, treatment, pathohistological signs.

 

СПИСОК ВИКОРИСТАНИХ ДЖЕРЕЛ/REFERENCES

 

1. Shivanthan 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. J Occup Med Toxicol. 2013 Apr 11;8(1):9. doi: 10.1186/1745-6673-8-9. PMID: 23578012; PMCID: PMC3637136.

2. Heaney CD, Wing S, Campbell RL, Caldwell D, Hopkins B, Richardson, et al. Relation between malodor, ambient hydrogen sulfide, and health in a community bordering a landfill. Environ Res. 2011 Aug;111(6):847-52. doi: 10.1016/j.envres.2011.05.021. Epub 2011 Jun 15. PMID: 21679938; PMCID: PMC3143289.

3. Elwood M. The Scientific Basis for Occupational Exposure Limits for Hydrogen Sulphide-A Critical Commentary. Int J Environ Res Public Health. 2021 Mar 11;18(6):2866. doi: 10.3390/ijerph18062866. PMID: 33799676; PMCID: PMC8001002.

4. Chaturvedi AK, Smith DR, Canfield DV. A fatality caused by accidental production of hydrogen sulfide. Forensic Sci Int. 2001 Dec 1;123(2-3):211–4. doi: 10.1016/s0379-0738(01)00552-7. PMID: 11728749.

5. Aventaggiato L, Colucci AP, Strisciullo G, Favalli F, Gagliano-Candela R. Lethal Hydrogen Sulfide poisoning in open space: An atypical case of asphyxiation of two workers. Forensic Sci Int. 2020 Mar;308:110122. doi: 10.1016/j.forsciint.2019.110122. Epub 2019 Dec 31. PMID: 31978694.

6. Ago M, Ago K, Ogata M. Two fatalities by hydrogen sulfide poisoning: variation of pathological and toxicological findings. Leg Med (Tokyo). 2008 May;10(3):148-52. doi: 10.1016/j.legalmed.2007.11.005. Epub 2008 Feb 8. PMID: 18262457.

7. Hendrickson RG, Chang A, Hamilton RJ. Co-worker fatalities from hydrogen sulfide. Am J Ind Med. 2004 Apr;45(4):346-50. doi: 10.1002/ajim.10355. PMID: 15029566.

8. Ramos AK, Fuentes A, Carvajal-Suarez M. Self-Reported Occupational Injuries and Perceived Occupational Health Problems among Latino Immigrant Swine Confinement Workers in Missouri. J Environ Public Health. 2018 Jun 19;2018:8710901. doi: 10.1155/2018/8710901. PMID: 30018647; PMCID: PMC6029498.

9. Davies V, Turner J, Greenway M. Toxic inhalational injury. BMJ Case Rep. 2020 Mar 10;13(3):e232875. doi: 10.1136/bcr-2019-232875. PMID: 32161078; PMCID: PMC7066608.

10. Park J, Kang T, Jin S, Heo Y, Kim K, Lee K, et al. Asphyxiation Incidents by Hydrogen Sulfide at Manure Storage Facilities of Swine Livestock Farms in Korea. J Agromedicine. 2016;21(2):144-8. doi: 10.1080/1059924X.2016.1141735. PMID: 26765950.

11. Ruder JB, Ward JG, Taylor S, Giles K, Higgins T, Haan JM. Hydrogen sulfide suicide: a new trend and threat to healthcare providers. J Burn Care Res. 2015 MarApr;36(2):e23-5. doi: 10.1097/BCR.0000000000000065. PMID: 25522151.

12. Maldonado CS, Weir A, Rumbeiha WK. A comprehensive review of treatments for hydrogen sulfide poisoning: past, present, and future. Toxicology Mechanisms and Methods, 2022 (3), 183–196. https://doi.org/10.1080/15376516.2022.2121192

13. Yang D, Chen G, Zhang R. Estimated Public Health Exposure to H2S Emissions from a Sour Gas Well Blowout in Kaixian County, China. Aerosol Air Qual. Res. 2006: 430-443. https://doi.org/10.4209/aaqr.2006.09.0018

14. OSHA. 2021. Accident search; Hydrogen sulfide. U. S. D. o. L. Occupational Safety and Health: 10.

15. OSHA. 2021. Hydrogen sulfide hazards; [accessed 2022 April 25]. https:// www.osha.gov/hydrogen-sulfide/hazards

16. Eghbal MA, Pennefather PS, O'Brien PJ. H2S cytotoxicity mechanism involves reactive oxygen species formation and mitochondrial depolarisation. Toxicology. 2004 Oct 15;203(1-3):69-76. doi: 10.1016/j.tox.2004.05.020. PMID: 15363583.

17. Jackson MR, Melideo SL, Jorns MS. Human sulfide:quinone oxidoreductase catalyzes the first step in hydrogen sulfide metabolism and produces a sulfane sulfur metabolite. Biochemistry. 2012 Aug 28;51(34):6804- 15. doi: 10.1021/bi300778t. Epub 2012 Aug  20. PMID: 22852582.

18. Jiang J, Chan A, Ali S, Saha A, Haushalter KJ, Lam WL, et al.-Mechanisms of Toxicity and Development of an Antidote. Sci Rep. 2016 Feb 15;6:20831. doi: 10.1038/srep20831. PMID: 26877209; PMCID: PMC4753484.

19. Truong DH, Eghbal MA, Hindmarsh W, Roth SH, O'Brien PJ. Molecular mechanisms of hydrogen sulfide toxicity. Drug Metab Rev. 2006;38(4):733-44. doi: 10.1080/03602530600959607. PMID: 17145698.

20. Kiss L, Deitch EA, Szabó C. Hydrogen sulfide decreases adenosine triphosphate levels in aortic rings and leads to vasorelaxation via metabolic inhibition. Life Sci. 2008 Oct 24;83(17-18):589-94. doi: 10.1016/j.lfs.2008.08.006. Epub 2008 Aug 28. PMID: 18790700; PMCID: PMC4225123.

21. Szabó C. Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov. 2007 Nov;6(11):917-35. doi: 10.1038/nrd2425. PMID: 17948022.

22. Geng P, Yu F, Tan D, Xu J, Yang Y, Xu M, et al. Involvement of claudin-5 in H2S-induced acute lung injury. J Toxicol Sci. 2020;45(5):293-304. doi: 10.2131/jts.45.293. PMID: 32404561.

23. Chen J, Chen S, Mao W. A Case of Survival: Myocardial Infarction and Ventricular Arrhythmia Induced by Severe Hydrogen Sulfide Poisoning. Cardiology. 2016;135(1):43- 7. doi: 10.1159/000445938. Epub 2016 May 19. PMID: 27193372.

24. Wang J, Zhang H, Su C, Chen J, Zhu B, Zhang H,et al. Dexamethasone ameliorates H₂S-induced acute lung injury by alleviating matrix metalloproteinase-2 and -9 expression. PLoS One. 2014 Apr 10;9(4):e94701. doi: 10.1371/journal.pone.0094701. PMID:  24722316; PMCID: PMC3983216.

25. Sonobe T, Chenuel B, Cooper TK, Haouzi P. Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue. PLoS One. 2015 Jun 26;10(6):e0131340. doi: 10.1371/journal.pone.0131340. PMID: 26115032; PMCID: PMC4482667.

26. Sonobe T, Haouzi P. H2S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores. Clin Toxicol (Phila). 2015 Jul;53(6):525-39. doi: 10.3109/15563650.2015.1043440. Epub 2015 May 12. PMID: 25965774; PMCID: PMC4469500.

27. Hendry-Hofer TB, Ng PC, McGrath AM, Mukai D, Brenner M, Mahon S, et al. Intramuscular aminotetrazole cobinamide as a treatment for inhaled hydrogen sulfide poisoning in a large swine model. Ann N Y Acad Sci. 2020 Nov;1479(1):159-167. doi: 10.1111/nyas.14339. Epub 2020 Mar 31. PMID: 32233102.

28. Hildebrandt TM, Grieshaber MK. Three enzymatic activities catalyze the oxidation of sulfide to thiosulfate in mammalian and invertebrate mitochondria. FEBS J. 2008 Jul;275(13):3352-61. doi: 10.1111/j.1742- 4658.2008.06482.x. Epub 2008 May 20. PMID: 18494801.

29. Miyazaki Y, Marutani E, Ikeda T, Ni X, Hanaoka K, Xian M, et al. A Sulfonyl Azide-Based Sulfide Scavenger Rescues Mice from Lethal Hydrogen Sulfide Intoxication. Toxicol Sci. 2021 Sep 28;183(2):393-403. doi: 10.1093/toxsci/kfab088. PMID: 34270781; PMCID:
PMC8478331.

30. Ng PC, Hendry-Hofer TB, Garrett N, Brenner M, Mahon SB, Maddry JK, et al. Intramuscular cobinamide versus saline for treatment of severe hydrogen sulfide toxicity in swine. Clin Toxicol (Phila). 2019 Mar;57(3):189-196. doi: 10.1080/15563650.2018.1504955. Epub 2018 Nov 15. PMID: 30430872; PMCID: PMC6540978.

31. Price WD, Price SM, Johnston M. Novel treatment of dihydrogen sulfide inhalation using hyperbaric oxygen during mass casualty. Undersea Hyperb Med. 2021 Second Quarter;48(2):153-156. doi: 10.22462/03.04.2021.5. PMID: 33975405.

32. Lim E, Mbowe O, Lee AS, Davis J. Effect of environmental exposure to hydrogen sulfide on central nervous system and respiratory function: a systematic review of human studies. Int J Occup Environ Health. 2016 Jan;22(1):80-90. doi: 10.1080/10773525.2016.1145881. Epub 2016 Apr 29. PMID: 27128692; PMCID: PMC4894269.

33. Tanaka S, Fujimoto S, Tamagaki Y, Wakayama K, Shimada K, Yoshikawa J. Bronchial injury and pulmonary edema caused by hydrogen sulfide poisoning. Am J Emerg Med. 1999 Jul;17(4):427-9. doi: 10.1016/s0735- 6757(99)90102-x. PMID: 10452448.

34. Mo W, Shen J, Huang X, Zhang Y, Zhang Z. Acute myocardial injury following hydrogen sulfide poisoning. Toxicol Ind Health. 2020 Oct;36(10):750-758. doi: 10.1177/0748233720945184. Epub 2020 Aug 6. PMID: 32757890.

35. Rumbeiha W, Whitley E, Anantharam P, Kim DS, Kanthasamy A. Acute hydrogen sulfide-induced neuropathology and neurological sequelae: challenges for translational neuroprotective research. Ann N Y Acad Sci. 2016 Aug;1378(1):5-16. doi: 10.1111/nyas.13148. Epub 2016 Jul 21. PMID: 27442775; PMCID: PMC5063677.

36. Haouzi P, Sonobe T, Judenherc-Haouzi A. Hydrogen sulfide intoxication induced brain injury and methylene blue. Neurobiol Dis. 2020 Jan;133:104474. doi: 10.1016/j.nbd.2019.05.013. Epub 2019 May 16. PMID: 31103557.

37. Haouzi P, Tubbs N, Cheung J, Judenherc-Haouzi A. Methylene Blue Administration During and After LifeThreatening Intoxication by Hydrogen Sulfide: Efficacy Studies in Adult Sheep and Mechanisms of Action. Toxicol Sci. 2019 Apr 1;168(2):443-459. doi: 10.1093/toxsci/kfy308. PMID: 30590764; PMCID: PMC6516679.

38. Adgate JL, Goldstein BD, McKenzie LM. Potential public health hazards, exposures and health effects from unconventional natural gas development. Environ Sci Technol. 2014;48(15):8307-20. doi: 10.1021/es404621d. Epub 2014 Feb 24. PMID: 24564405.

39. Wang L, Meng J, Wang C, Yang C, Wang Y, Li Y, et al. Hydrogen sulfide alleviates cigarette smoke-induced COPD through inhibition of the TGF-β1/smad pathway. Exp Biol Med (Maywood). 2020 Feb;245(3):190-200. doi: 10.1177/1535370220904342. Epub 2020 Feb 2. PMID: 32008357; PMCID: PMC7045331.

40. Libiad M, Yadav PK, Vitvitsky V, Martinov M, Banerjee R. Organization of the human mitochondrial hydrogen sulfide oxidation pathway. J Biol Chem. 2014 Nov 7;289(45):30901-10. doi: 10.1074/jbc.M114.602664. Epub 2014 Sep 15. PMID: 25225291; PMCID:
PMC4223297.

41. Anantharam P, Kim DS, Whitley EM, Mahama B, Imerman P, Padhi P, et al. Midazolam Efficacy Against Acute Hydrogen Sulfide-Induced Mortality and Neurotoxicity. J Med Toxicol. 2018 Mar;14(1):79-90. doi: 10.1007/s13181-017-0650-4. Epub 2018 Jan 9. PMID: 29318511; PMCID: PMC6013736.

42. Anantharam P, Whitley EM, Mahama B, Kim DS, Imerman PM, Shao D, et al. Characterizing a mouse model for evaluation of countermeasures against hydrogen sulfide-induced neurotoxicity and neurological sequelae. Ann N Y Acad Sci. 2017 Jul;1400(1):46-64. doi: 10.1111/nyas.13419. Epub 2017 Jul 18. PMID: 28719733; PMCID: PMC6383676.

43. Anantharam P, Whitley EM, Mahama B, Kim DS, Sarkar S, Santana C, et al. Cobinamide is effective for treatment of hydrogen sulfide-induced neurological sequelae in a mouse model. Ann N Y Acad Sci. 2017 Nov;1408(1):61-78. doi: 10.1111/nyas.13559. PMID: 29239480; PMCID: PMC5734662.

44. Matthew R Dent, Jason J. Rose, Jesús Tejero, Mark T Gladwin. Carbon Monoxide Poisoning: From Microbes to Therapeutics. ANNUAL REVIEW OF MEDICINE, 07 Jun 2024, Vol. 75, Issue 1, pages 337 – 351 https://doi.org/10.1146/annurev-med-052422-020045.

45. Li R, Dai X, Feng Z, Li Y, Zhao M, Liu J. Effect of toxic ligands on O2 binding to heme and their toxicity mechanism. Phys Chem Chem Phys. 2019;21(27):14957–63. DOI: 10.1039/C9CP02583A.

 

Стаття надійшла до редакції 24 червня 2024 р.

The article was received by the editors on June 24, 2024.