ArticleJournal of the American Heart Association2015
Thiosulfate Mediates Cytoprotective Effects of Hydrogen Sulfide Against Neuronal Ischemia.
Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Inorganic, Synthetic, Natural, and Innovative Hybrid Hydrogen Sulfide Donors and Inhibitors of Its Biosynthesis in the Treatment of Central and Peripheral Nervous System Injuries: A Systematic Analytical Review.International journal of molecular sciences · 2025Pooled it
- Gasotransmitters in the regulation of connexins in central and peripheral nervous system injuries.Medical gas research · 2027Review
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Unlocking the gasotransmitter: hydrogen sulfide as a multitarget regulator in ischemia-reperfusion injury.Medical gas research · 2026Review
- Development of an HInternational journal of molecular sciences · 2026Article
- Hydrogen sulfide in placental development and pregnancy disorders: mechanisms, therapeutic potential, and translational challenges.Reproductive biology and endocrinology : RB&E · 2025Review
- Sodium thiosulfate does not affect energy metabolism or organ (dys)function during resuscitation from murine trauma-and-hemorrhage.Intensive care medicine experimental · 2025Article
- Hydrogen sulfide aggravates neutrophil infiltration, vascular remodeling and elastase-induced abdominal aortic aneurysm in male mice.Communications medicine · 2025Article
- Thiosulphate sulfurtransferase: Biological roles and therapeutic potential.Redox biology · 2025Review
- Sodium Thiosulfate: An Innovative Multi-Target Repurposed Treatment Strategy for Late-Onset Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Deficiency of thiosulfate sulfurtransferase mediates the dysfunction of renal tubular mitochondrial fatty acid oxidation in diabetic kidney disease.Cell death and differentiation · 2024Article
- HScience advances · 2024Article
- Metabolic Effects of Sodium Thiosulfate During Resuscitation from Trauma and Hemorrhage in Cigarette-Smoke-Exposed Cystathionine-γ-Lyase Knockout Mice.Biomedicines · 2024Article
- The Role of Hydrogen Sulfide in iNOS and APP Localization and Expression in Neurons and Glial Cells Under Traumatic Effects: An Experimental Study with Bioinformatics Analysis and Biomodeling.International journal of molecular sciences · 2024Article
- Effect of Sodium Thiosulfate Pre-Treatment on Renal Ischemia-Reperfusion Injury in Kidney Transplantation.International journal of molecular sciences · 2024Article
- Role of hydrogen sulfide in health and disease.MedComm · 2024Review
- Acidity of persulfides and its modulation by the protein environments in sulfide quinone oxidoreductase and thiosulfate sulfurtransferase.The Journal of biological chemistry · 2024Article
- Targeted HBiomaterials research · 2024Article
- SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway.Cell stress & chaperones · 2023Review
- Evaluation of prophylactic efficacy of sodium thiosulfate in combating I/R injury in rat brain: exploring its efficiency further in vascular calcified brain slice model.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundHydrogen sulfide (H2S) exhibits protective effects in various disease models including cerebral ischemia-reperfusion (I/R) injury. Nonetheless, mechanisms and identity of molecules responsible for neuroprotective effects of H2S remain incompletely defined. In the current study, we observed that thiosulfate, an oxidation product of H2S, mediates protective effects of an H2S donor compound sodium sulfide (Na2S) against neuronal I/R injury. METHODS AND
resultsWe observed that thiosulfate in cell culture medium is not only required but also sufficient to mediate cytoprotective effects of Na2S against oxygen glucose deprivation and reoxygenation of human neuroblastoma cell line (SH-SY5Y) and murine primary cortical neurons. Systemic administration of sodium thiosulfate (STS) improved survival and neurological function of mice subjected to global cerebral I/R injury. Beneficial effects of STS, as well as Na2S, were associated with marked increase of thiosulfate, but not H2S, in plasma and brain tissues. These results suggest that thiosulfate is a circulating "carrier" molecule of beneficial effects of H2S. Protective effects of thiosulfate were associated with inhibition of caspase-3 activity by persulfidation at Cys163 in caspase-3. We discovered that an SLC13 family protein, sodium sulfate cotransporter 2 (SLC13A4, NaS-2), facilitates transport of thiosulfate, but not sulfide, across the cell membrane, regulating intracellular concentrations and thus mediating cytoprotective effects of Na2S and STS.
conclusionsThe protective effects of H2S are mediated by thiosulfate that is transported across cell membrane by NaS-2 and exerts antiapoptotic effects via persulfidation of caspase-3. Given the established safety track record, thiosulfate may be therapeutic against ischemic brain injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.