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Logo of jbcThe Journal of Biological Chemistry
J Biol Chem. 2010 June 11; 285(24): le10.
PMCID: PMC2881819

Reply to Savolainen: High Toxicity of Hydrogen Sulfide by the Inhibition of Mitochondrial Respiration

This is a response to a letter by Savolainen (1)

An important question is whether hydrogen sulfide donors, administered parenterally, might have toxic effects similar to those observed on exposure to hydrogen sulfide gas. The brief answer is no, because no effects on tissue of either endogenously produced hydrogen sulfide or hydrogen sulfide donors have been observed. Toxic levels in air are about 300 ppm. There is no direct way that ppm of H2S in the atmosphere can be converted to H2S levels in tissue, but it is interesting that Dorman et al. (2) found in rats no increase in H2S in hindbrain after 3 h of exposure to 400 ppm H2S. It is understandable that the lungs, where oxygen transfer to hemoglobin takes place, should be affected by high atmospheric levels of H2S. However, other tissues are exposed to H2S in the form of SH ions from H2S in solution. Normal endogenous levels have been reported to be of the order 50–160 μm (3). Our H2S donor molecules were tested and found to be efficacious in the 10–30 μm range. No toxicity was observed. Hu et al. (4) found no toxicity of the standard H2S donor NaSH at 300 μm. Thus there appears to be a very safe therapeutic range for synthetic H2S donors. It can be hoped that the considerable therapeutic potential of such donor compounds will not be retarded by baseless fears derived from toxicity of gaseous H2S. H2S needs to be understood as a vital endogenous antioxidant with neuroprotective and vascular relaxant properties.


1. Savolainen H. (2010) J. Biol. Chem.,
2. Dorman D. C., Moulin F. J., McManus B. E., Mahle K. C., James R. A., Struve M. F. (2002) Cytochrome oxidase inhibition induced by acute hydrogen sulfide inhalation. Correlation with tissue sulfide concentrations in the rat brain, liver, lung, and nasal epithelium. Toxicol. Sci. 65, 18–25 [PubMed]
3. Qu K., Lee S. W., Bian J. S., Low C. M., Wong P. T. (2008) Hydrogen sulfide: neurochemistry and neurobiology. Neurochem. Int. 52, 155–165 [PubMed]
4. Hu L. F., Wong P. T., Moore P. K., Bian J. S. (2007) Hydrogen sulfide attenuates lipopolysaccharide-induced inflammation by inhibition of p38 mitogen-activated protein kinase in microglia. J. Neurochem. 100, 1121–1128 [PubMed]

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