Urinary Thiosulfate Research Articles

A single dose of aged garlic extract did not change cerebral oxygenation and blood volume in older adults at cardiovascular risk factors

Backgroundand Aims: Ageing is associated with impaired endothelial function, which can negatively affect cerebral blood flow (CBF). The present study evaluated whether aged garlic extract (AGE) could improve cerebral oxygenation and blood volume due to the possible vasoactive effect. Methods and Results: Fourteen older adults were enrolled in a randomized, double-blind, cross-over study. Urinary thiosulfate and plasma nitrite was drawn, and participants ingested 2.4 g of AGE or placebo. A handgrip exercise protocol started 180 min after supplementation to induce brain activation, and cerebral oxygenation and blood volume were evaluated by near-infrared spectroscopy. After exercise, urinary thiosulfate and plasma nitrite were re-evaluated. AGE supplementation did not change cerebral oxygenation and blood volume. In addition, urinary thiosulfate and plasma nitrite remained unchanged after supplementation. Conclusion: A single dose of AGE (2.4 g) could not increase nitrite levels and cerebral oxygenation and blood volume in older adults at cardiovascular risk factors (NCT04008693).

Variability in Background Urinary Concentrations of the Hydrogen Sulfide Biomarker Thiosulfate.

Hydrogen sulfide is a toxic gas at high concentrations but has recently attracted attention as a naturally produced gaseous signaling molecule in various tissues of the human body, playing key physiological roles at low nanomolar concentrations. This has wide implications for chronic exposure to this gas in air at low levels far below toxicity. Thiosulfate is the currently used biomarker for exposure to hydrogen sulfide via inhalation but has been mainly employed for acute exposure. It is unknown how background thiosulfate concentrations vary on an intraindividual and interindividual basis in humans at normal ambient hydrogen sulfide levels (<1 μg m-3), which is key for the interpretation of its levels as biomarker for low-level hydrogen sulfide exposure. In the current work, the variability in thiosulfate urinary excretion in a total of 168 urine samples collected from eight volunteers over a period of 8 weeks was investigated. The determination of thiosulfate in urine was carried out by UHPLC-MS/MS. The total average concentration ± SD was 16 ± 6 μM (n = 168). Average urinary thiosulfate concentrations in the studied volunteers were within the range of 10-20 μM, but it was found that urinary thiosulfate can show significant day-to-day and week-to-week variability in some individuals (up to 10-fold), despite adjusting for urine specific gravity. In light of the presented variability data and previous studies about the lack of consistent response of thiosulfate to low levels of hydrogen sulfide inhalation exposure, and based on a review of the biochemistry of the production of thiosulfate and its various biological sources, it can be argued that thiosulfate might not be suitable as a biomarker for chronic environmental exposure to low levels of hydrogen sulfide via inhalation.

Improved microvascular reactivity after aged garlic extract intake is not mediated by hydrogen sulfide in older adults at risk for cardiovascular disease: a randomized clinical trial.

This study aimed to investigate the effects of AGE on microvascular reactivity, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in older individuals at high risk for cardiovascular disease (CVD). Urinary thiosulfate was also investigated as an indirect marker of endogenous hydrogen sulfide (H2S) synthesis. The study was conducted in a randomized, double-blind, crossover, and placebo-controlled way. Twenty-eight participants (14 male), 67 ± 6years old with CVD risk factors, ingested 2.4g of AGE or placebo (PLA). Near-infrared spectroscopy evaluated tissue oxygen saturation (StO2) during a vascular occlusion test (30s baseline, 5min occlusion, and 2min reperfusion). The upslope of StO2 signal after cuff release was calculated to measure microvascular reactivity. Urinary thiosulfate levels were measured using a high-performance liquid chromatography system. The upslope of StO2 was significantly faster after AGE (1.01 ± 0.37%s-1) intake compared to PLA (0.83 ± 0.35%s-1; P < 0.001; d = 0.50). Relative changes in Δ% SBP from pre- to post-AGE intake (-5.17 ± 5.77%) was significantly different compared to Δ% PLA (0.32 ± 5.99%; P = 0.001; d = 0.93). No significant changes in urinary thiosulfate concentrations were observed between interventions. Moreover, no significant gender effect in any parameter assessed was found. This study demonstrated that a single dose of AGE improved microvascular reactivity in older adults at risk of CVD despite such an effect was not linked with urinary thiosulfate levels. This trial was registered at clinicaltrials.gov as NCT04008693 (May 19, 2020).

Endogenous H2S production deficiencies lead to impaired renal erythropoietin production.

Patients suffering from chronic kidney disease (CKD) experience a number of associated comorbidities, including anemia. Relative deficiency in renal erythropoietin (EPO) production is thought to be a primary cause of anemia. Interestingly, CKD patients display low levels of hydrogen sulfide (H2S), an endogenously derived renal oxygen sensor. Previous in vitro experiments have revealed that H2S-deficient renal cell lines produce less EPO than wild-type renal cell lines during hypoxia. We postulated that H2S might be a primary mediator of EPO synthesis during hypoxia, which was tested using an in vivo murine model of whole-body hypoxia and in clinical samples obtained from CKD patients. Following a 72-hour period of hypoxia (11% O2), partial H2S knockout mice (lacking the H2S biosynthetic enzyme cystathionine γ-lyase [CSE]) displayed lower levels of hemoglobin, EPO and cystathionine-β-synthase (CBS) (another H2S biosynthetic enzyme) compared to wild-type mice, all of which was rescued by exogenous H2S supplementation. We also found that anemic CKD patients requiring exogenous EPO exhibited lower urinary thiosulfate levels compared to non-anemic CKD patients of similar CKD classification. Together, our results confirm an interplay between the actions of H2S during hypoxia and EPO production.

Microvascular circulatory dysregulation driven in part by cystathionine gamma-lyase: A new paradigm for cardiovascular compromise in the preterm newborn.

H2 S may explain the dysregulation of microvascular tone associated with poor outcome following preterm birth. In adult vasculature, H2 S is predominantly produced by CSE. We hypothesized that vascular CSE activity contributes to microvascular tone regulation during circulatory transition. Preterm (GA62) and full-term (GA69) guinea pig fetuses and neonates were studied. Microvascular blood flow was assessed by laser Doppler flowmetry. Thiosulfate, primary urinary metabolite of H2 S, was determined by high-performance liquid chromatography. Real-time H2 S production was assessed using a microrespiration system in fetal and postnatal (10, 24hours) skin and heart samples. CSE contribution was investigated by inhibition via propargylglycine. In preterm animals, postnatal H2 S production capacity in peripheral vasculature increased significantly and was significantly reduced by the inhibition of CSE. Urinary thiosulfate correlated with both microvascular blood flow and capacity of the vasculature to produce H2 S. H2 S produced via CSE did not correlate directly with microvascular blood flow. In preterm neonates, H2 S production increases during fetal-to-neonatal transition and CSE contribution to total H2 S increases postnatally. CSE-dependent mechanisms may therefore underpin the increase in H2 S production over the first 72hours of life in preterm human neonates, associated with both central and peripheral cardiovascular instability.

Urinary Excretion of Sulfur Metabolites and Risk of Cardiovascular Events and All-Cause Mortality in the General Population.

Aims: Thiosulfate and sulfate are metabolites of hydrogen sulfide (H2S), a gaseous signaling molecule with cardiovascular (CV) protective properties. Urinary thiosulfate excretion and sulfate excretion are associated with favorable disease outcome in high-risk patient groups. We investigated the relationship between urinary excretion of sulfur metabolites, and risk of CV events and all-cause mortality in the general population. Results: Subjects (n = 6839) of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study were followed prospectively. At baseline, 24-h urinary excretion of thiosulfate and sulfate was determined. Median urinary thiosulfate and sulfate excretion values were 1.27 (interquartile range [IQR] 0.89-2.37) μmol/24 h and 15.7 (IQR 12.0-20.3) mmol/24 h, respectively. Neither thiosulfate nor sulfate excretion showed an independent association with risk of CV events. Sulfate, but not thiosulfate, was inversely associated with risk of all-cause mortality, independent of potential confounders (hazard ratio 0.73 [95% confidence interval 0.63-0.84], p < 0.001). This association appeared most pronounced for normolipidemic subjects (pinteraction = 0.019). Innovation: The strong association between sulfate excretion and mortality in the general population emphasizes the (patho)physiological importance of sulfate or its precursor H2S. Conclusion: We hypothesize that urinary sulfate excretion, which is inversely associated with all-cause mortality in the general population, holds clinical relevance as a beneficial modulator in health and disease. Antioxid. Redox Signal. 30, 1999-2010.

Renal sulfate reabsorption in healthy individuals and renal transplant recipients.

Inorganic sulfate is essential for normal cellular function and its homeostasis is primarily regulated in the kidneys. However, little is known about renal sulfate handling in humans and particularly in populations with impaired kidney function such as renal transplant recipients (RTR). Hence, we aimed to assess sulfate reabsorption in kidney donors and RTR. Plasma and urinary sulfate were determined in 671 RTR and in 251 kidney donors. Tubular sulfate reabsorption (TSR) was defined as filtered load minus sulfate excretion and fractional sulfate reabsorption (FSR) was defined as 1‐fractional excretion. Linear regression analyses were employed to explore associations of FSR with baseline parameters and to identify the determinants of FSR in RTR. Compared to kidney donors, RTR had significantly lower TSR (15.2 [11.2–19.5] vs. 20.3 [16.7–26.3] μmol/min), and lower FSR (0.56 [0.48–0.64] vs. 0.64 [0.57–0.69]) (all P < 0.001). Kidney donation reduced both TSR and FSR by circa 50% and 25% respectively (both P < 0.001). In RTR and donors, both TSR and FSR associated positively with renal function. In RTR, FSR was independently associated with urinary thiosulfate (β = −0.18; P = 0.002), growth hormone (β = 0.12; P = 0.007), the intakes of alcohol (β = −0.14; P = 0.002), methionine (β = −0.34; P < 0.001), cysteine (β = −0.41; P < 0.001), and vitamin D (β = −0.14; P = 0.009). In conclusion, TSR and FSR are lower in RTR compared to kidney donors and both associated with renal function. Additionally, FSR is determined by various dietary and metabolic factors. Future research should determine the mechanisms behind sulfate handling in humans and the prognostic value of renal sulfate reabsorption in RTR.

Screening of a clinically and biochemically diagnosed SOD patient using exome sequencing: A case report with a mutations/variations analysis approach

BackgroundSulfite oxidase deficiency (SOD) is a rare neurometabolic inherited disorder causing severe delay in developmental stages and premature death. The disease follows an autosomal recessive pattern of inheritance and causes deficiency in the activity of sulfite oxidase, an enzyme that normally catalyzes conversion of sulfite to sulfate. Aim of the studySOD is an underdiagnosed disorder and its diagnosis can be difficult in young infants as early clinical features and neuroimaging changes may imitate some common diseases. Since the prognosis of the disease is poor, using exome sequencing as a powerful and efficient strategy for identifying the genes underlying rare mendelian disorders can provide important knowledge about early diagnosis, disease mechanisms, biological pathways, and potential therapeutic targets. Patients and methodsIn this study, a case who was a newborn infant boy with suspected SOD and his healthy parents were recruited for exome sequencing. The first laboratory reports of the patient were positive urine sulfite, elevated urinary thiosulfate, and high levels of plasma lactate and pyruvate. The patient also presented some symptoms such as intractable seizures, abnormal tone, feeding difficulties, profound mental retardation, abnormal respiratory drive, aspiration pneumonia, microcephaly, and dislocated ocular lenses. The genomic DNA of the patient and his parents was extracted from peripheral blood lymphocytes as targets for exome sequencing, performed by Axeq Technologies (Amsterdam, the Netherlands). ResultsThe results showed no single predominate mutation in the SUOX gene as one of the candidate genes involved in the catabolism of sulfur-containing amino acids. The same results obtained in the molybdenum cofactor biosynthetic genes (MOCS1, MOCS2, and GEPH genes). Instead, the results revealed that causal variations are present in genes underlying in different biochemical pathways among which the sulfur metabolism, signaling and signal transduction, and transcription pathways are of higher importance. ConclusionIn this study, several classes of genes were introduced as candidate genes involved in SOD. However, further studies are necessary to examine the reported genes in more details on how these genes may relate to each other and contribute to the pathology of SOD disease.

Urinary thiosulfate as failed prostate cancer biomarker - an exemplary multicenter re-evaluation study.

In 2013, thiosulfate in urine has been proposed as promising prostate cancer (PCa) biomarker. However, a missing comparison with other proven PCa markers suggested a re-evaluation study. Therefore, together with the authors from the initial study, the diagnostic accuracy of thiosulfate was compared with that of urinary prostate cancer associated 3 (PCA3), serum prostate health index (Phi), and percent free prostate-specific antigen (%fPSA). Thiosulfate was further measured in a multicenter approach to exclude center-related biases. Thiosulfate, calculated as ratio of thiosulfate to urinary creatinine (TS/Crea ratio), was measured in two cohorts in a total of 269 patients. In the retrospective study (n=160) PCA3, Phi, PSA, and %fPSA were compared with the TS/Crea ratio between patients with and without PCa according to the prostate needle biopsy results. The second prospective cohort included 109 patients from four centers. The median TS/Crea ratio was not statistically different between the patients with and without PCa. The receiver-operating characteristics showed that the TS/Crea ratio was unable to discriminate between patients with and without PCa in contrast to %fPSA, Phi, and PCA3. In all four centers, the low median TS/Crea ratios (<1 mmol/mol) in both patient cohorts were confirmed and thiosulfate was again not able to distinguish between them (p-values, 0.13-0.90). This study could not confirm the previously observed high median TS/Crea ratio in PCa patients in comparison to non-PCa patients. Thiosulfate subsequently failed as PCa biomarker while PCA3 and Phi showed the expected diagnostic improvement.

Cognitive functions changes among Egyptian sewage network workers

The current work aimed at investigating the cognitive functions impairment among workers of sewer networks due to exposure to hydrogen sulfide (H(2)S) and the relation of this impairment, if any, to the level of H(2)S exposure biomarker 'urinary thiosulfate.' Besides, the validity of using Mini Mental State Examination (MMSE) as screening test for cognitive impairment among the exposed workers was tested. The work was conducted among 33 sewage network maintenance male workers and a matched unexposed control group (n = 30). The participants were subjected to clinical neurological history, estimation of urinary thiosulfate, and assessment of cognitive dysfunction by using neurophysiological (simple reaction time, P300 test) and neuropsychological tests (Wechsler Memory Scale) and frontal executive functions tests. Clinical neurological history revealed significantly higher neurological symptoms (headache, memory defects, lack of concentration) among exposed workers compared to their controls (p < 0.05). Exposed workers had significantly prolonged simple reaction time and delayed P300 latency and showed poor performance of most of neuropsychological tests. Marked elevation of urinary thiosulfate was observed among the exposed workers (p < 0.001) but this elevation was not correlated with the duration of exposure or any of the other measured parameters. Exposed workers had significantly lower mean value of MMSE scoring than that of the controls (p < 0.001). In conclusion, exposure to H( 2)S among sewer network workers is associated with cognitive impairment, which can be screened by applying MMSE as a simple rapid test for H( 2)S occupationally exposed workers.

COGNITIVE FUNCTIONS CHANGES AMONG EGYPTIAN SEWAGE NETWORK WORKERS

Objectives: The current work aimed at investigating the cognitive functions impairment among workers of sewer networks due to exposure to H2S and the relation of this impairment ,if any, to the level of H2S exposure biomarker “urinary thiosulfate”. Besides, the validity of using Mini Mental State Examination (MMSE) as screening test for cognitive impairment among the exposed workers was tested.Subjects: The work was conducted among 33 sewage network maintenance male workers and a matched unexposed control group (n= 30).Methods: The participants were subjected to clinical neurological history, estimation of urinary thiosulfate, and assessment of cognitive dysfunction by using neurophysiological (simple reaction time, P300 test) and neuropsychological tests (Wechsler MemoryScale) and frontal executive functions tests. Results: Clinical neurological history revealed significantly higher neurological symptoms(headache, memory defects, lack of concentration) among exposed workers compared to their controls (P< 0.05). Exposed workers had significantly prolonged simple reaction time and delayed P300 latency and showed poor performance of most of neuropsychological tests. Marked elevation of urinary thiosulfate was observed among theexposed workers (P< 0.001) but this elevation was not correlated with the duration of exposure or any of the other measured parameters. Exposed workers had significantly lower mean value of MMSE scoring than that of the controls (P<0.001). Conclusion: Exposure to H2S among sewer network workers is associated with cognitive impairment which can be screened by applying MMSE as a simple rapid test for hydrogen sulfide occupationally exposed workers.

Urinary thiosulfate determined by suppressed ion chromatography with conductimetric detection

Thiosulfate is a naturally occurring product of sulfur metabolism. Assays of urinary thiosulfate have been based on the reaction with cyanide to form thiocyanate. However, matrix interferences and background variation in endogenous thiocyanate excretion place constraints on this method for determination of physiological amounts of thiosulfate in urine. We describe a column-switching ion chromatographic separation for urinary thiosulfate that allows for sensitive and accurate detection by ion conductimetry. In 20 adult volunteers, we found a lower urinary thiosulfate (8.50±7.39 μmol/24 h, mean±S.D.) than others have described, although the upward skew of the results (median, 6.90; range, 0.84-32 μmol/ 24 h) was similar. However, we have not observed any of the interfaces and the sensitivityof our technique (<0.2 μmol/24 h) allows for detection of thiosulfate in all control samples. This sort of methodological improvement will be essential for any study of physiological thiosulfate metabolism.

Improved colorimetric determination of urinary thiosulfate to study intermediate sulfur metabolism in humans

Journal Article Improved colorimetric determination of urinary thiosulfate to study intermediate sulfur metabolism in humans Get access V Voroteliak, V Voroteliak Search for other works by this author on: Oxford Academic Google Scholar D M Cowley, D M Cowley Search for other works by this author on: Oxford Academic Google Scholar T H Florin T H Florin Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 39, Issue 12, 1 December 1993, Pages 2533–2534, https://doi.org/10.1093/clinchem/39.12.2533 Published: 01 December 1993

A simple screening test for sulfite oxidase deficiency: Detection of urinary thiosulfate by a modification of sörbo's method

A simple screening test for sulfite oxidase deficiency: Detection of urinary thiosulfate by a modification of sörbo's method