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Journal of the American Society of... Jun 2009An uncontrolled trial reported that sodium thiosulfate reduces formation of calcium kidney stones in humans, but this has not been established in a controlled human...
An uncontrolled trial reported that sodium thiosulfate reduces formation of calcium kidney stones in humans, but this has not been established in a controlled human study or animal model. Using the genetic hypercalciuric rat, an animal model of calcium phosphate stone formation, we studied the effect of sodium thiosulfate on urine chemistries and stone formation. We fed genetic hypercalciuric rats normal food with or without sodium thiosulfate for 18 wk and measured urine chemistries, supersaturation, and the upper limit of metastability of urine. Eleven of 12 untreated rats formed stones compared with only three of 12 thiosulfate-treated rats (P < 0.002). Urine calcium and phosphorus were higher and urine citrate and volume were lower in the thiosulfate-treated rats, changes that would increase calcium phosphate supersaturation. Thiosulfate treatment lowered urine pH, which would lower calcium phosphate supersaturation. Overall, there were no statistically significant differences in calcium phosphate supersaturation or upper limit of metastability between thiosulfate-treated and control rats. In vitro, thiosulfate only minimally affected ionized calcium, suggesting a mechanism of action other than calcium chelation. In summary, sodium thiosulfate reduces calcium phosphate stone formation in the genetic hypercalciuric rat. Controlled trials testing the efficacy and safety of sodium thiosulfate for recurrent kidney stones in humans are needed.
Topics: Animals; Anions; Antioxidants; Calcium Phosphates; Nephrolithiasis; Rats; Thiosulfates; Urinalysis
PubMed: 19369406
DOI: 10.1681/ASN.2008070754 -
The Science of the Total Environment Nov 2020Biological sulfate and thiosulfate reduction under haloalkaline conditions can be applied to treat waste streams from biodesulfurization systems. However, the lack of...
Biological sulfate and thiosulfate reduction under haloalkaline conditions can be applied to treat waste streams from biodesulfurization systems. However, the lack of microbial aggregation under haloalkaline conditions limits the volumetric rates of sulfate and thiosulfate reducing bioreactors. As biomass retention in haloalkaline bioreactors has not been studied before, sand was chosen as a biomass carrier material to increase cell retention and consequently raise the volumetric rates. The results showed that ~10 fold higher biomass concentrations could be achieved with sand, compared to previous studies without carrier addition. The volumetric rates of sulfate/thiosulfate reduction increased approximately 4.5 times. Biomass attachment to the sand was restricted to cavities within the sand particles. Acetate produced by acetogenic bacteria from H and CO was used as carbon source for biomass growth, while formate that was also produced from H and CO enhanced sulfate reduction. The microbial community composition was analyzed by 16S rRNA gene amplicon sequencing, and Tindallia related bacteria were probably responsible for formate formation from hydrogen. The community attached to the sand particles was similar to the suspended fraction, but the relative abundance of sequences most closely related to Desulfohalobiaceae was much higher in the attached fraction compared to the suspended fraction (30% and 13%, respectively). The results indicated that even though the biomass attachment to sand was poor, it still increased the biomass concentration and consequently the sulfate and thiosulfate reduction volumetric rates.
Topics: Biomass; Bioreactors; Oxidation-Reduction; RNA, Ribosomal, 16S; Sand; Sulfates; Thiosulfates
PubMed: 32736107
DOI: 10.1016/j.scitotenv.2020.141017 -
Scientific Reports Jul 2022Thiosulfate sulfurtransferase (TST, EC 2.8.1.1), also known as Rhodanese, was initially discovered as a cyanide detoxification enzyme. However, it was recently also...
Thiosulfate sulfurtransferase (TST, EC 2.8.1.1), also known as Rhodanese, was initially discovered as a cyanide detoxification enzyme. However, it was recently also found to be a genetic predictor of resistance to obesity-related type 2 diabetes. Diabetes type 2 is characterized by progressive loss of adequate β-cell insulin secretion and onset of insulin resistance with increased insulin demand, which contributes to the development of hyperglycemia. Diabetic complications have been replicated in adult hyperglycemic zebrafish, including retinopathy, nephropathy, impaired wound healing, metabolic memory, and sensory axonal degeneration. Pancreatic and duodenal homeobox 1 (Pdx1) is a key component in pancreas development and mature beta cell function and survival. Pdx1 knockdown or knockout in zebrafish induces hyperglycemia and is accompanied by organ alterations similar to clinical diabetic retinopathy and diabetic nephropathy. Here we show that pdx1-knockdown zebrafish embryos and larvae survived after incubation with thiosulfate and no obvious morphological alterations were observed. Importantly, incubation with hTST and thiosulfate rescued the hyperglycemic phenotype in pdx1-knockdown zebrafish pronephros. Activation of the mitochondrial TST pathway might be a promising option for therapeutic intervention in diabetes and its organ complications.
Topics: Animals; Diabetes Mellitus, Type 2; Hyperglycemia; Models, Theoretical; Pronephros; Thiosulfate Sulfurtransferase; Thiosulfates; Zebrafish
PubMed: 35840638
DOI: 10.1038/s41598-022-16320-1 -
PloS One 2014Urinary sulfate (SO4(2-)) and thiosulfate (S2O3(2-)) can potentially bind with calcium and decrease kidney stone risk. We modeled the effects of these species on the...
BACKGROUND
Urinary sulfate (SO4(2-)) and thiosulfate (S2O3(2-)) can potentially bind with calcium and decrease kidney stone risk. We modeled the effects of these species on the concentration of ionized calcium (iCa) and on supersaturation (SS) of calcium oxalate (CaOx) and calcium phosphate (CaP), and measured their in vitro effects on iCa and the upper limit of stability (ULM) of these salts.
METHODS
Urine data from 4 different types of stone patients were obtained from the Mayo Nephrology Clinic (Model 1). A second data set was obtained from healthy controls and hypercalciuric stone formers in the literature who had been treated with sodium thiosulfate (STS) (Model 2). The Joint Expert Speciation System (JESS) was used to calculate iCa and SS. In Model 1, these parameters were calculated as a function of sulfate and thiosulfate concentrations. In Model 2, data from pre- and post STS urines were analyzed. ULM and iCa were determined in human urine as a function of sulfate and thiosulfate concentrations.
RESULTS
Calculated iCa and SS values for all calcium salts decreased with increasing sulfate concentration. Thiosulfate had no effect on these parameters. In Model 2, calculated iCa and CaOx SS increased after STS treatment, but CaP SS decreased, perhaps due to a decrease in pH after STS treatment. In confirmatory in vitro experiments supplemental sulfate, but not thiosulfate, significantly increased the calcium needed to achieve the ULM of CaP and tended to increase the oxalate needed to reach the ULM of CaOx. Sulfate also significantly decreased iCa in human urine, while thiosulfate had no effect.
CONCLUSION
Increasing urinary sulfate could theoretically reduce CaOx and CaP stone risk. Although STS may reduce CaP stone risk by decreasing urinary pH, it might also paradoxically increase iCa and CaOx SS. As such, STS may not be a viable treatment option for stone disease.
Topics: Adult; Aged; Calcium; Case-Control Studies; Female; Humans; Male; Middle Aged; Models, Biological; Thiosulfates; Urinary Calculi
PubMed: 25061988
DOI: 10.1371/journal.pone.0103602 -
American Journal of Physiology. Heart... Aug 2017Recent reports have revealed that hydrogen sulfide (HS) exerts critical actions to promote cardiovascular homeostasis and health. Thiosulfate is one of the products...
Recent reports have revealed that hydrogen sulfide (HS) exerts critical actions to promote cardiovascular homeostasis and health. Thiosulfate is one of the products formed during oxidative HS metabolism, and thiosulfate has been used extensively and safely to treat calcific uremic arteriopathy in dialysis patients. Yet despite its significance, fundamental questions regarding how thiosulfate and HS interact during redox signaling remain unanswered. In the present study, we examined the effect of exogenous thiosulfate on hypoxia-induced HS metabolite bioavailability in human umbilical vein endothelial cells (HUVECs). Under hypoxic conditions, we observed a decrease of GSH and GSSG levels in HUVECs at 0.5 and 4 h as well as decreased free HS and acid-labile sulfide and increased bound sulfide at all time points. Treatment with exogenous thiosulfate significantly decreased the ratio of GSH/GSSG to total sulfide of HUVECs under 0.5 h of hypoxia but significantly increased this ratio in HUVECs under 4 h of hypoxia. These responses reveal that thiosulfate has different effects at low and high doses and under different O tensions. In addition, treatment with thiosulfate also diminished VEGF-induced cystathionine-γ-lyase expression and reduced VEGF-induced HUVEC proliferation under both normoxic and hypoxic conditions. These results indicate that thiosulfate can modulate HS metabolites and signaling under various culture conditions that impact angiogenic activity. Thus, thiosulfate may serve as a unique sulfide donor to modulate endothelial responses under pathophysiological conditions involving angiogenesis. This report provides new evidence that different levels of exogenous thiosulfate dynamically change discrete sulfide biochemical metabolite bioavailability in endothelial cells under normoxia or hypoxia, acting in a slow manner to modulate sulfide metabolites. Moreover, our findings also reveal that thiosulfate surprisingly inhibits VEGF-dependent endothelial cell proliferation associated with a reduction in cystathionine-γ-lyase protein levels.
Topics: Angiogenesis Inducing Agents; Angiogenesis Inhibitors; Biological Availability; Cell Hypoxia; Cell Proliferation; Cells, Cultured; Cellular Microenvironment; Cystathionine gamma-Lyase; Dose-Response Relationship, Drug; Glutathione; Glutathione Disulfide; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Sulfide; Neovascularization, Physiologic; Oxidation-Reduction; Signal Transduction; Thiosulfates; Time Factors; Vascular Endothelial Growth Factor A
PubMed: 28550177
DOI: 10.1152/ajpheart.00723.2016 -
PLoS Biology Apr 2024Uptake of thiosulfate ions as an inorganic sulfur source from the environment is important for bacterial sulfur assimilation. Recently, a selective thiosulfate uptake...
Uptake of thiosulfate ions as an inorganic sulfur source from the environment is important for bacterial sulfur assimilation. Recently, a selective thiosulfate uptake pathway involving a membrane protein YeeE (TsuA) in Escherichia coli was characterized. YeeE-like proteins are conserved in some bacteria, archaea, and eukaryotes. However, the precise function of YeeE, along with its potential partner protein in the thiosulfate ion uptake pathway, remained unclear. Here, we assessed selective thiosulfate transport via Spirochaeta thermophila YeeE in vitro and characterized E. coli YeeD (TsuB) as an adjacent and essential protein for YeeE-mediated thiosulfate uptake in vivo. We further showed that S. thermophila YeeD possesses thiosulfate decomposition activity and that a conserved cysteine in YeeD was modified to several forms in the presence of thiosulfate. Finally, the crystal structures of S. thermophila YeeE-YeeD fusion proteins at 3.34-Å and 2.60-Å resolutions revealed their interactions. The association was evaluated by a binding assay using purified S. thermophila YeeE and YeeD. Based on these results, a model of the sophisticated uptake of thiosulfate ions by YeeE and YeeD is proposed.
Topics: Thiosulfates; Bacterial Proteins; Escherichia coli; Escherichia coli Proteins; Biological Transport; Protein Binding; Cysteine; Amino Acid Sequence; Crystallography, X-Ray
PubMed: 38656967
DOI: 10.1371/journal.pbio.3002601 -
Clinical Journal of the American... Jun 2011Vascular calcification is a major cause of morbidity and mortality in dialysis patients. Human and animal studies indicate that sodium thiosulfate (STS) may prevent the...
BACKGROUND AND OBJECTIVES
Vascular calcification is a major cause of morbidity and mortality in dialysis patients. Human and animal studies indicate that sodium thiosulfate (STS) may prevent the progression of vascular calcifications. The pharmacokinetics of STS in hemodialysis patients has not been investigated yet.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
STS was given intravenously to 10 hemodialysis patients on- and off-hemodialysis. Additionally, STS was applied to 9 healthy volunteers once intravenously and once orally. Thiosulfate concentrations were measured by using a specific and sensitive HPLC method.
RESULTS
In volunteers and patients, mean endogenous thiosulfate baseline concentrations were 5.5 ± 1.82 versus 7.1 ± 2.7 μmol/L. Renal clearance was high in volunteers (1.86 ± 0.45 ml/min per kg) and reflected GFR. Nonrenal clearance was slightly, but not significantly, higher in volunteers (2.25 ± 0.32 ml/min per kg) than in anuric patients (2.04 ± 0.72 ml/min per kg). Hemodialysis clearance of STS was 2.62 ± 1.01 ml/min per kg. On the basis of the nonrenal clearance and the thiosulfate steady-state serum concentrations, a mean endogenous thiosulfate generation rate of 14.6 nmol/min per kg was calculated in patients. After oral application, only 4% of STS was recovered in urine of volunteers, reflecting a low bioavailability of 7.6% (0.8% to 26%).
CONCLUSIONS
Given the low and variable bioavailability of oral STS, only intravenous STS should be prescribed today. The biologic relevance of the high hemodialysis clearance for the optimal time point of STS dosing awaits clarification of the mechanisms of action of STS.
Topics: Administration, Oral; Adult; Aged; Biological Availability; Biotransformation; Cardiovascular Agents; Chi-Square Distribution; Chromatography, High Pressure Liquid; Female; Glomerular Filtration Rate; Humans; Injections, Intravenous; Kidney; Kidney Diseases; Male; Middle Aged; Models, Biological; Renal Dialysis; Switzerland; Thiosulfates
PubMed: 21566113
DOI: 10.2215/CJN.10241110 -
Microbiome Nov 2023Heterotrophic microbes inhabiting the dark ocean largely depend on the settling of organic matter from the sunlit ocean. However, this sinking of organic materials is...
BACKGROUND
Heterotrophic microbes inhabiting the dark ocean largely depend on the settling of organic matter from the sunlit ocean. However, this sinking of organic materials is insufficient to cover their demand for energy and alternative sources such as chemoautotrophy have been proposed. Reduced sulfur compounds, such as thiosulfate, are a potential energy source for both auto- and heterotrophic marine prokaryotes.
METHODS
Seawater samples were collected from Labrador Sea Water (LSW, ~ 2000 m depth) in the North Atlantic and incubated in the dark at in situ temperature unamended, amended with 1 µM thiosulfate, or with 1 µM thiosulfate plus 10 µM glucose and 10 µM acetate (thiosulfate plus dissolved organic matter, DOM). Inorganic carbon fixation was measured in the different treatments and samples for metatranscriptomic analyses were collected after 1 h and 72 h of incubation.
RESULTS
Amendment of LSW with thiosulfate and thiosulfate plus DOM enhanced prokaryotic inorganic carbon fixation. The energy generated via chemoautotrophy and heterotrophy in the amended prokaryotic communities was used for the biosynthesis of glycogen and phospholipids as storage molecules. The addition of thiosulfate stimulated unclassified bacteria, sulfur-oxidizing Deltaproteobacteria (SAR324 cluster bacteria), Epsilonproteobacteria (Sulfurimonas sp.), and Gammaproteobacteria (SUP05 cluster bacteria), whereas, the amendment with thiosulfate plus DOM stimulated typically copiotrophic Gammaproteobacteria (closely related to Vibrio sp. and Pseudoalteromonas sp.).
CONCLUSIONS
The gene expression pattern of thiosulfate utilizing microbes specifically of genes involved in energy production via sulfur oxidation and coupled to CO fixation pathways coincided with the change in the transcriptional profile of the heterotrophic prokaryotic community (genes involved in promoting energy storage), suggesting a fine-tuned metabolic interplay between chemoautotrophic and heterotrophic microbes in the dark ocean. Video Abstract.
Topics: Heterotrophic Processes; Thiosulfates; Carbon; Gammaproteobacteria; Sulfur; Carbon Cycle
PubMed: 37925458
DOI: 10.1186/s40168-023-01688-7 -
Microbiology (Reading, England) Apr 2020Chemolithotrophic sulfur oxidation represents a significant part of the biogeochemical cycling of this element. Due to its long evolutionary history, this ancient...
Chemolithotrophic sulfur oxidation represents a significant part of the biogeochemical cycling of this element. Due to its long evolutionary history, this ancient metabolism is well known for its extensive mechanistic and phylogenetic diversification across a diverse taxonomic spectrum. Here we carried out whole-genome sequencing and analysis of a new betaproteobacterial isolate, SBSA, which is found to oxidize thiosulfate via the formation of tetrathionate as an intermediate. The 4.7 Mb SBSA genome was found to encompass a operon, plus single thiosulfate dehydrogenase () and sulfite : acceptor oxidoreductase () genes. Recombination-based knockout of revealed that the entire thiosulfate is first converted to tetrathionate by the activity of thiosulfate dehydrogenase (TsdA) and the Sox pathway is not functional in this bacterium despite the presence of all necessary genes. The ∆ and ∆ knockout mutants exhibited a wild-type-like phenotype for thiosulfate/tetrathionate oxidation, whereas ∆ ∆ and ::Kan mutants only oxidized thiosulfate up to tetrathionate intermediate and had complete impairment in tetrathionate oxidation. The substrate-dependent O consumption rate of whole cells and the sulfur-oxidizing enzyme activities of cell-free extracts, measured in the presence/absence of thiol inhibitors/glutathione, indicated that glutathione plays a key role in SBSA tetrathionate oxidation. The present findings collectively indicate that the potential glutathione : tetrathionate coupling in involves a novel enzymatic component, which is different from the dual-functional thiol dehydrotransferase (ThdT), while subsequent oxidation of the sulfur intermediates produced (e.g. glutathione : sulfodisulfane molecules) may proceed via the iterative action of .
Topics: Alcaligenaceae; Bacterial Proteins; Chemoautotrophic Growth; Genome, Bacterial; Glutathione; Mutation; Oxidation-Reduction; Oxidoreductases; Oxygen; Sulfhydryl Compounds; Sulfites; Sulfur; Tetrathionic Acid; Thiosulfates
PubMed: 31999239
DOI: 10.1099/mic.0.000890 -
MBio Aug 2022Zero-valent sulfur (ZVS) distributes widely in the deep-sea cold seep, which is an important immediate in the sulfur cycle of cold seep. In our previous work, we...
Zero-valent sulfur (ZVS) distributes widely in the deep-sea cold seep, which is an important immediate in the sulfur cycle of cold seep. In our previous work, we described a novel thiosulfate oxidation pathway determined by thiosulfate dehydrogenase (TsdA) and thiosulfohydrolase (SoxB) mediating the conversion of thiosulfate to ZVS in the deep-sea cold seep bacterium Erythrobacter flavus 21-3. However, the occurrence and ecological role of this pathway in the deep-sea cold seep were obscure. Here, we cultured E. flavus 21-3 in the deep-sea cold seep for 10 days and demonstrated its capability of forming ZVS in the field. Based on proteomic, stoichiometric analyses and microscopic observation, we found that this thiosulfate oxidation pathway benefited E. flavus 21-3 to adapt the cold seep conditions. Notably, ~25% metagenomes assembled genomes derived from the shallow sediments of cold seeps contained both and , where presented abundant sulfur metabolism-related genes and active sulfur cycle. Our results suggested that the thiosulfate oxidation pathway determined by TsdA and SoxB existed across many bacteria inhabiting in the cold seep and frequently used by microbes to take part in the active cold seep biogeochemical sulfur cycle. The contribution of microbes to the deep-sea cold seep sulfur cycle has received considerable attention in recent years. In the previous study, we isolated E. flavus 21-3 from deep-sea cold seep sediments and described a novel thiosulfate oxidation pathway in the laboratorial condition. It provided a new clue about the formation of ZVS in the cold seep. However, because of huge differences between laboratory and environment, whether bacteria perform the same thiosulfate oxidation pathway in the deep-sea cold seep should be further confirmed. In this work, we verified that E. flavus 21-3 formed ZVS using this pathway in deep-sea cold seep through cultivation, which confirmed the importance of this thiosulfate oxidation pathway and provided an approach to study the real metabolism of deep-sea microorganisms.
Topics: Bacteria; Oxidation-Reduction; Phylogeny; Proteomics; Sulfur; Thiosulfates
PubMed: 35852328
DOI: 10.1128/mbio.00143-22