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"Researchers have developed a novel antidote to treat hydrogen sulfide poisoning. It is hoped that this innovation will save the lives of workers and rescue personnel. ...
A team ... created the novel therapeutic using artificial haem-model compounds that have a higher affinity for sulfide than human haem. ‘We are trying to synthesise biomedical compounds to mimic the haemoglobin function like the oxygen binding,’ ... This work builds on previous research ..., which identified two complexes that successfully treated carbon monoxide and hydrogen cyanide poisoning in mice. ..."
"... Hydrogen sulfide binds strongly to heme-containing enzymes in the cell and blocks the process of respiration, causing rapid death at higher concentrations. Now, researchers at Kyoto’s Doshisha University have developed an artificial heme-model compound that has a high affinity for hydrogen sulfide and binds to it at a much faster rate than human met-hemoglobin. This compound, met-hemoCD-I, was used to successfully treat hydrogen sulfide-induced toxicity in mice, indicating its potential as an antidote. ..."
From the abstract:
"Hydrogen sulfide is a lethal toxic gas that disrupts cellular respiration in the mitochondrial system. Currently, no antidote is available for the clinical treatment of hydrogen sulfide poisoning. In this study, we investigated the function of iron(III)porphyrin complexes as hydrogen sulfide scavengers in water and evaluated their potential use as therapeutic agents for hydrogen sulfide poisoning. The compounds, named met-hemoCD-P and met-hemoCD-I, are composed of iron(III)porphyrin complexed with per-methylated β-cyclodextrin dimers that contain a pyridine (met-hemoCD-P) or imidazole axial fifth ligand that is coordinated to Fe(III) (met-hemoCD-I). These compounds formed stable HS–Fe(III) complexes under physiological conditions, with binding constants of 1.2 × 105 and 2.5 × 106 M–1 for met-hemoCD-P and met-hemoCD-I, respectively. The binding constant of met-hemoCD-I was 10-times higher than that reported for native human met-hemoglobin at pH 7.4 and 25oC.
Electron paramagnetic resonance (EPR) spectroscopy and H2S quantification assays revealed that after SH– was coordinated to met-hemoCD-I, it was efficiently converted to nontoxic sulfite and sulfate ions via homolytic cleavage of the HS–Fe(III) bond followed by aerobic oxidation.
Mouse animal experiments revealed that the survival rate was significantly improved when NaSH-treated mice were injected with met-hemoCD-I. After the injection, mitochondrial CcO function in brain and heart tissues recovered, and met-hemoCD-I injected was excreted in the urine without chemical decomposition."
Research News: A Novel Heme-Model Compound that Treats Lethal Gas Poisoning (original news release) "Researchers from Japan have developed a synthetic, nontoxic antidote to safely treat hydrogen sulfide poisoning"
Combining an iron porphyrin with a cyclodextrin dimer allowed hydrogen sulfide to be scavenged from the blood of poisoned mice
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