Hydrogen Sulfide Metabolism Research Articles

Regulation of mitochondrial hydrogen sulfide metabolism by endogenous modulators of persulfide dioxygenase

Regulation of mitochondrial hydrogen sulfide metabolism by endogenous modulators of persulfide dioxygenase

β-Aminobutyric Acid Effectively Postpones Senescence of Strawberry Fruit by Regulating Metabolism of NO, H2S, Ascorbic Acid, and ABA

Current researchis focused on the influence of β-aminobutyric acid (BABA) on the metabolism of nitric oxide (NO), hydrogen sulfide (H2S), ascorbic acid, and abscisic acid (ABA) in strawberry fruit. The increases in ion leakage and malondialdehyde (MDA) concentration in strawberry fruit and the degradation of chlorophyll in the sepals of the fruit were markedly inhibited by BABA at 20 mM. BABA-immersed fruit exhibited lower activities and expressions of polygalacturonase (PG), pectinmethylesterase (PME), and ethylene biosynthetic enzymes compared to the control. Furthermore, BABA immersion evidently upgraded the metabolic levels of NO and H2S, including the enzymatic activities and intermediary contents of metabolites, which collectively enhanced the levels of endogenous NO and H2S contents in strawberry fruit. The high enzymatic activities and gene expressions of the AsA biosynthesis pathway jointly maintained AsA accumulation in the BABA-treated sample. The application of BABA led to a decrease in ABA concentration, which was associated with reduced activities and gene expression levels of key enzymes participating in ABA metabolism. Our experimental observations showed that immersion with BABA may be a highly promising means to delay senescence and reduce natural decay in strawberry fruit, and the alleviation in senescence using BABA may be attributed to the modulation of NO, H2S, AsA, and ABA metabolism.

Hydrogen Peroxide Promotes Tomato Leaf Senescence by Regulating Antioxidant System and Hydrogen Sulfide Metabolism.

Hydrogen peroxide (H2O2) is relatively stable among ROS (reactive oxygen species) and could act as a signal in plant cells. In the present work, detached tomato leaves were treated with exogenous H2O2 at 10 mmol/L for 8 h to study the mechanism of how H2O2 regulates leaf senescence. The data indicated that H2O2 treatment significantly accelerated the degradation of chlorophyll and led to the upregulation of the expression of leaf senescence-related genes (NYC1, PAO, PPH, SGR1, SAG12 and SAG15) during leaf senescence. H2O2 treatment also induced the accumulation of H2O2 and malondialdehyde (MDA), decreased POD and SOD enzyme activities and inhibited H2S production by reducing the expression of LCD1/2 and DCD1/2. A correlation analysis indicated that H2O2 was significantly and negatively correlated with chlorophyll, the expression of leaf senescence-related genes, and LCD1/2 and DCD1/2. The principal component analysis (PCA) results show that H2S showed the highest load value followed by O2•-, H2O2, DCD1, SAG15, etc. Therefore, these findings provide a basis for studying the role of H2O2 in regulating detached tomato leaf senescence and demonstrated that H2O2 plays a positive role in the senescence of detached leaves by repressing antioxidant enzymes and H2S production.

First clinical evidence that trimethylsulfonium can serve as a biomarker for the production of the signaling molecule hydrogen sulfide

BackgroundHydrogen sulfide (H2S) is established as the third gaseous signaling molecule and is known to be overproduced in down syndrome (DS) due to the extra copy of the CBS gene on chromosome 21, which has been suggested to contribute to the clinical manifestation of this condition. We recently discovered trimethylsulfonium (TMS) in human urine and highlighted its potential as a selective methylation metabolite of endogenously produced H2S, but the clinical utility of this novel metabolite has not been previously investigated. We hypothesize that the elevation of H2S production in DS would be reflected by an elevation in the methylation product TMS. MethodsTo test this hypothesis, a case-control study was performed and the urinary levels of TMS were found to be higher in the DS group (geo. mean 4.5 nM, 95 % CI 2.4–3.9) than in the control (N) group (3.1 nM, 3.5–6.0), p-value 0.01, whereas the commonly used biomarker of hydrogen sulfide, thiosulfate, failed to reflect this alteration in H2S production (15 µM (N) vs. 13 µM (DS), p-value 0.24. ResultsThe observed association is in line with the proposed hypothesis and provides first clinical evidence of the utility of TMS as a novel and more sensitive biomarker for the endogenous production of the third gaseous signaling molecule than the conventionally used biomarker thiosulfate, which is heavily dependent on bacterial hydrogen sulfide production. ConclusionThis work shows that TMS must be explored in clinical conditions where altered metabolism of hydrogen sulfide is implicated.

The role of mitochondrial bioenergy and system glutathione in deficiency of Coenzyme Q and Complex I

Cytokine Coenzyme Q10 (CoQ10) is an insoluble coenzyme that is a component of the electron transport chain and is involved in oxidative phosphorylation in mitochondria. By a decrease in CoQ10, the energy requirements of the cell are not fully covered: cell division slows down, and the processes of tissue renewal and regeneration are disrupted. In our work, we used a model of mice CoQ9 Knockin (R239X). In homozygous mutant mice, a strong decrease in CoQ7 protein and the accumulation of dimethoxyubiquinone are observed. An impairment of hydrogen sulfide metabolism was previously identified as a significant pathomechanism of primary Coenzyme Q deficiency. The experimental results showed that the disruption of sulfide and glutathione metabolism in Coq9R239X mice is directly dependent on CoQ levels. Therefore, changes in dietary sulfur-containing amino acids do not alter sulfide metabolism and the glutathione system in Coq9R239X mice. As our experiments have shown, an increase in total glutathione is observed only in symptomatic brain tissue. It can be assumed that this is due to oxidative stress in the symptomatic brain tissue, which is often found with mitochondrial dysfunction.

Thiosulfate sulfurtransferase deficiency promotes oxidative distress and aberrant NRF2 function in the brain

Thiosulfate sulfurtransferase (TST, EC 2.8.1.1) was discovered as an enzyme that detoxifies cyanide by conversion to thiocyanate (rhodanide) using thiosulfate as substrate; this rhodanese activity was subsequently identified to be almost exclusively located in mitochondria. More recently, the emphasis regarding its function has shifted to hydrogen sulfide metabolism, antioxidant defense, and mitochondrial function in the context of protective biological processes against oxidative distress. While TST has been described to play an important role in liver and colon, its function in the brain remains obscure. In the present study, we therefore sought to address its potential involvement in maintaining cerebral redox balance in a murine model of global TST deficiency (Tst−/− mice), primarily focusing on characterizing the biochemical phenotype of TST loss in relation to neuronal activity and sensitivity to oxidative stress under basal conditions. Here, we show that TST deficiency is associated with a perturbation of the reactive species interactome in the brain cortex secondary to altered ROS and RSS (specifically, polysulfide) generation as well as mitochondrial OXPHOS remodeling. These changes were accompanied by aberrant Nrf2-Keap1 expression and thiol-dependent antioxidant function. Upon challenging mice with the redox-active herbicide paraquat (25 mg/kg i.p. for 24 h), Tst−/− mice displayed a lower antioxidant capacity compared to wildtype controls (C57BL/6J mice). These results provide a first glimpse into the molecular and metabolic changes of TST deficiency in the brain and suggest that pathophysiological conditions associated with aberrant TST expression and/or activity renders neurons more susceptible to oxidative stress-related malfunction.

Design and synthesis of two iridium(Ⅲ) complex probes for rapid sensing of hydrogen sulfide

Hydrogen sulfide (H2S) is an important sulfur-containing signaling molecule in the human body, as well as a highly toxic gas that is soluble in water. A variety of pathological processes are associated with abnormal metabolism of hydrogen sulfide, so it is very important to develop an assay that can rapidly and specifically detect H2S. In this work, two iridium(Ⅲ) complexes were designed and synthesized using ester groups as reaction sites for recognition of H2S. As the H2S concentration increased, the photoluminescence of the probe was rapidly quenched within 5seconds, with a detection limit as low as 0.45 μM. Among them, the probe Ir1, whose luminescence was located in the visible region, had been successfully used for the detection of trace amounts of H2S in water samples with a recovery rate of 92.5 ~ 104.0% and a relative standard deviation (RSD, n=5) of < 2.8%. The luminescence of probe Ir2 was located in the near-infrared region, which could avoid the interference of biological autofluorescence and be successfully used for luminescence imaging of H2S in HeLa cells. This study provided a promising method for rapid detection of trace H2S in water samples and cellular microenvironments.

Rhodanese-Fold Containing Proteins in Humans: Not Just Key Players in Sulfur Trafficking.

The Rhodanese-fold is a ubiquitous structural domain present in various protein subfamilies associated with different physiological functions or pathophysiological conditions in humans. Proteins harboring a Rhodanese domain are diverse in terms of domain architecture, with some representatives exhibiting one or several Rhodanese domains, fused or not to other structural domains. The most famous Rhodanese domains are catalytically active, thanks to an active-site loop containing an essential cysteine residue which allows for catalyzing sulfur transfer reactions involved in sulfur trafficking, hydrogen sulfide metabolism, biosynthesis of molybdenum cofactor, thio-modification of tRNAs or protein urmylation. In addition, they also catalyse phosphatase reactions linked to cell cycle regulation, and recent advances proposed a new role into tRNA hydroxylation, illustrating the catalytic versatility of Rhodanese domain. To date, no exhaustive analysis of Rhodanese containing protein equipment from humans is available. In this review, we focus on structural and biochemical properties of human-active Rhodanese-containing proteins, in order to provide a picture of their established or putative key roles in many essential biological functions.

Morphological changes in the kidney tissue of rats with experimental diabetes mellitus and during correction with metformin and modulators of hydrogen sulfide metabolism

Annotation. Metformin is widely used for pharmacocorrection of diabetic nephropathy in type 2 diabetes mellitus. However, the mechanisms of the protective effect of metformin on the kidneys remain unclear, in particular, the contribution of the hydrogen sulfide system to metformin’s nephroprotective effect is unknown. Therefore, the aim of our study was to assess the role of metformin and its combination with modulators of hydrogen sulfide metabolism in the correction of histological changes in the kidneys of streptozotocin-induced diabetic rats. The studies were performed on 30 white non-linear male rats, which were divided into five groups: 1 group - control; group 2 – animals with experimental diabetes, which was initiated by a single intraperitoneal injection of streptozotocin (40 mg/kg of weight) in 0.1 M citrate buffer (pH 4.5); Group 3 - animals with experimental diabetes, which were treated with metformin (500 mg/kg/day, intragastrically) from the 3rd to the 28th day; Group 4 - animals with diabetes mellitus, which, along with metformin, were administered NaHS (56 μmol/kg/day, intragastrically); Group 5 - animals with diabetes mellitus, which, along with metformin, were administered propargylglycine (442 μmol/kg/day, intragastrically). Histological examinations were performed according to generally accepted methods using an Olympus BX-41 light microscope (Olympus Europe GmbH, Japan). It was found that animals with experimental diabetes develop nephrosclerosis and glomerular hypertrophy, damage to the endothelium of kidney vessels, interstitial inflammation, and edema, and dystrophic and necrobiotic changes in the glomeruli. The administration of metformin to diabetic animals reduced the severity of nephrosclerosis, glomerular hypertrophy, destruction of vascular endotheliocytes, inflammation, and damage to the glomerular apparatus. The use of the hydrogen sulfide donor NaHS increased the nephroprotective activity of metformin, while the introduction of the hydrogen sulfide synthesis inhibitor- propargylglycine, significantly reduced the protective effect of metformin on the kidneys. The obtained results of the histological examination justify the feasibility of implementation of a hydrogen sulfide donor in order to potentiate the renoprotective effect of metformin.

Retracted: Alteration of Intestinal Microbiota and Hydrogen Sulfide Metabolism in Patients with Hashimoto’s Thyroiditis

Retracted: Alteration of Intestinal Microbiota and Hydrogen Sulfide Metabolism in Patients with Hashimoto’s Thyroiditis

Alteration of Intestinal Microbiota and Hydrogen Sulfide Metabolism in Patients with Hashimoto's Thyroiditis.

To analyze the intestinal microbiota and H2S levels in patients with HT. Twenty euthyroid HT patients and twenty healthy control individuals were recruited. Fecal samples were collected, and the microbiota was examined using 16S RNA gene sequencing. We also collected serum samples to examine the H2S levels. Compared with patients with HT, the ACE and Chao indices were significantly lower in healthy controls (P=0.04, 0.03, respectively). The microbial composition of the HT group differed significantly from that of the healthy group. We observed a significant increase in the proportions of Bacteroides, Fusobacterium, Sutterella, and Veillonella in patients with HT (P < 0.05). Linear discriminant analysis and effect size analysis also revealed that Bacteroides and Ralstonia were enriched in patients with HT. Additionally, patients with HT had significantly lower H2S levels than healthy controls (P < 0.005). The enrichment of H2S anabolism was linked to the alteration of intestinal microbiota in patients with HT. We demonstrated that patients with HT have aberrant intestinal microbiome and that H2S anabolism may contribute to HT pathogenesis.

β-Cyclodextrin-Based Nitrosoglutathione Improves the Storage Quality of Peach by Regulating the Metabolism of Endogenous Nitric Oxide, Hydrogen Sulfide, and Phenylpropane

Nitrosoglutathione (GSNO) and β-cyclodextrin (β-CD) exhibit positive roles in regulating fruit quality. However, there are few reports about the effects of GSNO and β-CD on enhancing storability and boosting nitric oxide (NO), hydrogen sulfide (H2S), and phenylpropane metabolism in fruits during storage. “Xintaihong” peach were treated with 0.5, 1.0, 1.5 mmol L−1 GSNO in 0.5% (w/v) β-CD solution (GSNO/β-CD). The effects of GSNO/β-CD on endogenous NO, H2S, and phenylpropane metabolism were investigated. Treatment with GSNO/β-CD increased the color difference of peach and inhibited the increase of respiratory intensity, weight loss, and relative conductivity. Treatment with 1.0 mmol L−1 GSNO/β-CD increased the nitric oxide synthase (NOS-like) activity and L-arginine content, thereby promoting the accumulation of endogenous NO. By improving the activities of L-cysteine desulfhydrylase (L-CD), O-acetylserine sulfur lyase (OAS-TL), serine acetyltransferase (SAT), GSNO/β-CD increased the content of endogenous H2S in peach. Treatment with GSNO/β-CD increased the activities of phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL), and cinnamic acid-4-hydroxylase (C4H), promoted the increase of total phenols, flavonoids, and lignin in peach. These results indicated that GSNO/β-CD treatment better maintained the quality of peach by improving the metabolism of endogenous NO, H2S, and phenylpropane during storage.

The effect of hydrogen sulfide metabolism modulators on CSE gene expression, levels of proinflammatory and profibrotic mediators, morphological changes in cardiovascular system of rats in experimental obesity

Hydrogen sulfide (H 2 S) is considered to be a multifunctional mediator. Disorders of H 2 S synthesis are related to the pathogenesis of cardio- vascular pathology. Approaches to H2 S metabolism correction in cardiovascular system in obesity are not defined. The aim of study: to estimate the effect of H 2 S metabolism modulators on CSE gene expression, levels of proinflammatory and profibrotic mediators, morphological changes in cardiovascular system of rats in experimental obe- sity (EO). Methods. The experiments were carried out on 70 white non-linear male rats. The care and use of laboratory animals were approved by the general principles of bioethics (Strasbourg, 1986). EO was induced by a high-calorie diet application during 10 weeks. The 8-10-th weeks of the experiment was the period when H 2 S metabolism modulators were administered. The expression of CSE gene, levels of visfatin, TNFα, endothelin-1 and morphological changes were estimated in cardiovascular system. Results. EO results in CSE gene oppression in myocardium and aorta, therewith elevation of visfatin and TNFα levels in myocardium occurs, serum level of endothelin-1 increases, morphological features of cardiomyopathy re- veal furthermore. H 2 S donor (NaHS) and cofactors (α-lipoic acid, zinc sulfate) upregulate CSE gene expression, perform an adjusting effect on biochemical disturbances, reduce signs of cardiomyopathy, while propargylglycine (cysta- thionine-γ-lyase inhibitor) induces the opposite effects. Conclusions. H 2 S is involved in regulation of inflammatory and fibrogenic mediators in cardiovascular system in obesity. Cofactors of H 2 S metabolism effectively correct cardiometabolic disorders in this condition

Hyperoxic Injury in Human Primary Airway Epithelial Cell Is Associated with Changes in Hydrogen Sulfide Metabolism

Hyperoxic Injury in Human Primary Airway Epithelial Cell Is Associated with Changes in Hydrogen Sulfide Metabolism

Changes in the Metabolism of Nitric Oxide, Hydrogen Sulfide of the Oral Fluid Taking into Account Age and Dental Status

The relevance of the study is conditioned by the prevalence of dental pathology, its complicated course in senior age and the search for the age-associated metabolic markers of oral fluid.&#x0D; Objective. The aim of the study is: to determine the age peculiarities of the content of nitric oxide and hydrogen sulfide metabolism in the oral fluid of patients, taking into account their dental status.&#x0D; Materials and Methods. Indicators of nitric oxide metabolism, L-arginine/arginase, hydrogen sulfide content in oral fluid, dental status of different aged people under conditions of intact dentitions, their defects and against the background of correction with different types of dentures, were studied.&#x0D; Results. It was determined that with age, changes in oral fluid are characterized by an increase in nitrite ion, the amount of nitrites and nitrates, increasing the formation of peroxynitrite against the background of lower levels of L-arginine and hydrogen sulfide, inhibition of arginase activity. The results obtained are confirmed by the presence of close correlations between the concentrations of hydrogen sulfide and peroxynitrite (reverse, strong), caries intensity and: the total level of nitrites and nitrates (direct, strong), peroxynitrite content (direct, medium strength).&#x0D; Conclusion. The studied biomarkers of oral fluid depend more on age, hygienic condition of the oral cavity, intensity of dental caries and defects of dentitions than types of dentures. Therefore, age-related changes in the biochemical composition of oral fluid, metabolic, somatic, comorbid pathologies are likely to be a trigger for structural-functional disorders of the dental-maxillofacial system.

Dual modulating effects of hydrogen sulfide on gastrointestinal tract and efficacy-toxicity transformation of hydrogen sulfide-mediated drugs

Hydrogen sulfide is one of the most important signal transduction molecules in the body. Its anabolism and catabolism in the gastrointestinal tract(GT) are extremely high, and its role in the physiological and pathological process of the GT is fairly complicated. The study reviewed recent literature on hydrogen sulfide and GT, and proposed that hydrogen sulfide exerted dual modulating effects in the GT; specifically, it promoted the functions of the GT at low concentrations while damaged the GT at high concentrations. Hydrogen sulfide donors or metabolic modifiers exerted their therapeutic effects by restoring the metabolic homeostasis of hydrogen sulfide, and extended their efficacy to other tissues through hydrogen sulfide related gut-axis. Additionally, drugs could deviate hydrogen sulfide metabolism from the normal state due to their instability of structure, local over exposure and/or excessive pharmacological effects, thus inducing toxic and side effects or transforming therapeutic effects into toxic and side effects. This study provided references for the deep research on physiological and pathological mechanisms of hydrogen sulfide and facilitated the development of hydrogen sulfide-related drugs and discovery of their toxicity and efficacy mechanism.

The effect of modulators of hydrogen sulfide metabolism on morphological changes in kidneys of rats with high-calorie diet-induced obesity

Annotation. Obesity is one of the factors in the development of chronic kidney disease. Hydrogen sulfide (H2S) plays an important role in regulating the functional state of the kidneys, and its endogenous production is disrupted in obesity. The search for effective and safe correctors of H2S metabolism in the kidneys in obesity is relevant. The aim of the study was to establish the effect of potential modulators of H2S metabolism on biochemical and morphological changes in the kidneys of rats with high-calorie-diet-induced obesity (DIO). The experiments were performed on 60 white male laboratory rats in accordance with the principles of bioethics (Strasbourg, 1986; Kyiv, 2001). DIO was modeled using a high-calorie high-fat diet (39.5% fat per calorie). Metabolic correction was performed with H2S metabolism modulators (zinc sulfate, sodium thiosulfate, lipoic acid, taurine). Control rats received a standard diet (10.5% fat per calorie). Somatometric parameters, H2S level, morphological changes of kidney tissue were determined. Statistical processing was performed in the package IBM Statistics SPSS 26, differences were assessed in the Kruskel-Wallis test at a significance level of p&lt;0.05. It was found that the development of DIO was accompanied by a decrease in the concentration of H2S in the kidneys (1.9 times, p&lt;0.001), characteristic morphological changes in renal tissue with damage of the glomerular and tubular apparatus, severe inflammatory reaction of the parenchyma, endothelial damage and vascular structure. All metabolic correctors increased the level of H2S in the kidneys and inhibited the progression of nephropathy under the conditions of DIO. Zinc sulfate and lipoic acid were the most effective in preserving the structural elements of the renal parenchyma, while sodium thiosulfate and taurine were less effective.

Vagus nerve stimulated by microbiota-derived hydrogen sulfide mediates the regulation of berberine on microglia in transient middle cerebral artery occlusion rats.

Amelioration of neuroinflammation via modulating microglia is a promising approach for cerebral ischemia therapy. The aim of the present study was to explore gut-brain axis signals in berberine-modulating microglia polarization following cerebral ischemia. The potential pathway was determined through analyzing the activation of the vagus nerve, hydrogen sulfide (H2 S) metabolism, and cysteine persulfides of transient receptor potential vanilloid 1 (TRPV1) receptor. The cerebral microenvironment feature was explored with a metabolomics assay. The data indicated that berberine ameliorated behavioral deficiency in transient middle cerebral artery occlusion rats through modulating microglia polarization and neuroinflammation depending on microbiota. Enhanced vagus nerve activity following berberine treatment was blocked by antibiotic cocktails, capsazepine, or sodium molybdate, respectively. Berberine-induced H2 S production was responsible for vagus nerve stimulation achieved through assimilatory and dissimilatory sulfate reduction with increased synthetic enzymes. Sulfation of the TRPV1 receptor resulted in vagus nerve activation and promoted the c-fos and ChAT in the nucleus tractus solitaries with berberine. Sphingolipid metabolism is the primary metabolic characteristic with berberine in the cerebral cortex, hippocampus, and cerebral spinal fluid disrupted by antibiotics. Berberine, in conclusion, modulates microglia polarization in a microbiota-dependent manner. H2 S stimulates the vagus nerve through TRPV1 is responsible for the berberine-induced gut-brain axis signal transmission. Sphingolipid metabolism might mediate the neuroinflammation amelioration following vagus afferent fiber activation.

Rapid determination of hydrogen sulfide-related metabolites in human urine by UHPLC-ESI-MS/MS with fluorinated ion-pairing reagents

Although primarily considered as a toxic gas, hydrogen sulfide is naturally produced in humans from the amino acid cysteine in low quantities and is commonly referred to as the “third gaseous signaling molecule”. There is a need to establish reliable biomarkers for exposure to hydrogen sulfide in human matrices not only at toxic levels but also at trace levels. Herein, we report optimized analytical methods for the direct determination of three compounds related to hydrogen sulfide metabolism in human urine without sample preparation; namely, trimethylsulfonium, thiosulfate, and cystine. The methods were based on ion-pair ultra-high performance liquid chromatography (UHPLC) with an anionic fluorinated acid or a cationic fluoroalkylamine, a member of a new generation of ion-pairing reagents, and detection by the electrospray ionization tandem mass spectrometry (ESI-MS/MS). Rapid chromatographic separation was achieved in 2–3 min with limits of detection of 0.1, 2.5, and 50 nmol L−1 (nM) for trimethylsulfonium, cystine, and thiosulfate, respectively. Isotopically labeled internal standards were used for each analyte to account for matrix effects and qualifier ions were employed to ensure selectivity. The method was validated for recovery (generally within 80–120%) and repeatability (RSD% 1.0–10%), and applied to investigate the normal concentrations of the three analytes in forty morning first-pass urine samples of healthy volunteers.

Modulation of Human Hydrogen Sulfide Metabolism by Micronutrients, Preliminary Data.

Background:Hydrogen sulfide (H2S) is a pivotal gasotransmitter networking with nitric oxide (NO) and carbon monoxide (CO) to regulate basic homeostatic functions. It is released by the alternative pathways of transulfuration by the enzymes Cystathionine Beta Synthase (CBS) and Cystathionine Gamma Lyase (CSE), and by Cysteine AminoTransferase (CAT)/ 3-Mercaptopyruvate Sulfur Transferase (3MPST). A non-enzymatic, intravascular release is also in place. We retrospectively investigated the possibility to modulate the endogenous H2S release and signaling in humans by a dietary manipulation with supplemented micronutrients (L-cystine, Taurine and pyridoxal 5-phopsphate/P5P).Methods:Patients referring for antiaging purposes underwent a 10-day supplementation. Blood was collected at baseline and after treatment and the metabolome was investigated by mass spectrometry to monitor the changes in the metabolites reporting on H2S metabolism and related pathways.Results:Data were available from 6 middle aged subjects (2 women). Micronutrients increased 3-mercaptopyruvate (P = .03), reporting on the activity of CAT that provides the substrate for H2S release within mitochondria by 3MPST, decreased lanthionine (P = .024), reporting the release of H2S from CBS, and had no significant effect of H2S release from CSE. This is compatible with a homeostatic balancing. We also recorded a strong increase of reporters of H2S-induced pathways including 5-MethylTHF (P = .001) and SAME (P = .022), reporting on methylation capacity, and of BH4 (P = .021) and BH2 (P = .028) reporting on nitric oxide metabolism. These activations may be explained by the concomitant induction of non-enzymatic release of H2S.Conclusions:Although the current evidences are weak and will need to be confirmed, the effect of micronutrients was compatible with an increase of the H2S endogenous release and signaling within the control of homeostatic mechanisms, further endorsing the role of feeding in health and disease. These effects might result in a H2S boosting effect in case of defective activity of pathologic origin, which should be checked in duly designed clinical trials.