Reply to Savolainen: High Toxicity of Hydrogen Sulfide by the Inhibition of Mitochondrial Respiration
Bibliographic record
Abstract
This is a response to a letter by Savolainen (1Savolainen H. J. Biol. Chem. 2010; (http://www.jbc.org/cgi/content/full/285/24/le9)Google Scholar) 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. (2Dorman D.C. Moulin F.J. McManus B.E. Mahle K.C. James R.A. Struve M.F. 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. 2002; 65: 18-25Crossref PubMed Scopus (292) Google Scholar) 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 (3Qu K. Lee S.W. Bian J.S. Low C.M. Wong P.T. Hydrogen sulfide: neurochemistry and neurobiology..Neurochem. Int. 2008; 52: 155-165Crossref PubMed Scopus (233) Google Scholar). Our H2S donor molecules were tested and found to be efficacious in the 10–30 μm range. No toxicity was observed. Hu et al. (4Hu L.F. Wong P.T. Moore P.K. Bian J.S. Hydrogen sulfide attenuates lipopolysaccharide-induced inflammation by inhibition of p38 mitogen-activated protein kinase in microglia..J. Neurochem. 2007; 100: 1121-1128Crossref PubMed Scopus (266) Google Scholar) 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.022 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.005 |
| Scholarly communication | 0.004 | 0.008 |
| Open science | 0.004 | 0.003 |
| Research integrity | 0.029 | 0.055 |
| Insufficient payload (model declined to judge) | 0.003 | 0.006 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".