New antidote for hydrogen sulfide gas

Hydrogen sulfide, a colourless gas that smells like rotten eggs, is produced naturally from decaying matter. This gas is lethal to breathe in, and hydrogen sulfide present in high concentrations can cause death very rapidly.

Its relative density is also greater than air, causing it to accumulate at lower altitudes and posing an enormous threat to workers at sites, such as manholes, sewage systems and mining operations.

Why is hydrogen sulfide so dangerous? It binds strongly to the heme-containing cytochrome c oxidase (CcO) enzyme and blocks the cellular process of aerobic (oxygen-dependent) respiration.
What is even more concerning is that, as of now, there is no identified antidote that can treat hydrogen sulfide poisoning. Hence, there is an urgent need to develop therapeutic agents that can be stored for long durations and are effective against hydrogen sulfide poisoning immediately.

A study  published online on December 10, 2024, in Scientific Reports has proposed a novel antidote for hydrogen sulfide poisoning.

Researchers decided to tackle this problem by using artificial heme-model compounds that would have a higher affinity towards hydrogen sulfide than the native hemes present in our bodies.

They  have developed and studied synthetic heme-model compounds (hemoCDs) over the last two decades.

In this study, they decided to test if  two of those complexes had the potential to "scavenge" hydrogen sulfide in an aqueous medium. Interestingly, they found that met-hemoCD-I in particular had a very high affinity for hydrogen sulfide under normal physiological conditions—almost 10 times higher than that of human met-hemoglobin.

Met-hemoCD-I was able to convert toxic hydrogen sulfide into nontoxic sulfite and sulfate ions, indicating that it could be used to treat hydrogen sulfide poisoning.

To test this antidote, they injected hydrogen sulfide-treated mice with met-hemoCD-I. The results were very promising—mice injected with met-hemoCD-I showed improved survival rates compared to mice that were not given the antidote. Additionally, CcO activity in the brain and heart tissues (which had decreased because of poisoning) recovered and returned to normal.
Another aspect of met-hemoCD-I that makes it a very promising antidote is its demonstrated safety—it was found that injected met-hemoCD-I was excreted in the urine of the rats without undergoing any chemical decomposition in their body.

The results of this study show that hemoCD-Twins could be used as a powerful antidote to treat carbon monoxide, hydrogen cyanide, and now hydrogen sulfide poisoning without the risk of any side effects.
Using hemoCD-Twins, we can provide one powerful solution for multiple gas poisoning, even if the cause of poisoning is unknown.
Clinical trials are about to be started with this antidote.

Met-hemoCD-I detoxified hydrogen sulfide by converting it into the less harmful compounds sulfite and sulfate. Credit: The authors of this study

 Nakagami, A., et al. Detoxification of hydrogen sulfide by synthetic heme model compounds, Scientific Reports (2024). DOI: 10.1038/s41598-024-80511-1