Serum H2S Levels Research Articles

H2S donor GYY4137 mitigates sFlt-1-induced hypertension and vascular dysfunction in pregnant rats†.

Gestational hypertension, often associated with elevated soluble Fms-related receptor tyrosine kinase 1 (sFlt-1), poses significant risks to both maternal and fetal health. Hydrogen sulfide (H2S), a gasotransmitter, has demonstrated blood pressure-lowering effects in hypertensive animals and humans. However, its role in pregnancy-induced hypertension remains unclear. This study investigated the impact of GYY4137, a slow-release H2S donor, on sFlt-1-induced hypertension in pregnant rats . Pregnant rats were administered sFlt-1 (6μg/kg/day, intravenously) or vehicle from gestation day (GD) 12-20. A subset of these groups received GYY4137 ( 50mg/kg/day, intraperitoneal) from GD 16-20. Serum H2S levels, mean arterial blood pressure, uterine artery blood flow, and vascular reactivity were assessed. Elevated sFlt-1 reduced both maternal weight gain and serum H2S levels. GYY4137 treatment restored both weight gain and H2S levels in sFlt-1 dams. sFlt-1 increased mean arterial pressure and decreased uterine artery blood flow in pregnant rats. However, treatment with GYY4137 normalized blood pressure and restored uterine blood flow in sFlt-1 dams. sFlt-1 dams exhibited heightened vasoconstriction to phenylephrine and GYY4137 significantly mitigated the exaggerated vascular contraction. Notably, sFlt-1 impaired endothelium-dependent relaxation, while GYY4137 attenuated this impairment by upregulating eNOS protein levels and enhancing vasorelaxation in uterine arteries. GYY4137 mitigated sFlt-1-induced fetal growth restriction. In conclusion, sFlt-1 mediated hypertension is associated with decreased H2S levels. Replenishing H2S with the donor GYY4137 mitigates hypertension and improves vascular function and fetal growth outcomes. This suggests modulation of H2S could offer a novel therapeutic strategy for managing gestational hypertension and adverse fetal effects.

Racial and Ethnic Minorities With Acute Pancreatitis Live in Neighborhoods With Higher Social Vulnerability Scores.

The primary objective was to determine differences in Social Vulnerability Index (SVI) scores among minorities (African-Americans and Hispanics) with acute pancreatitis (AP) compared with non-Hispanic whites (NHWs) with AP. The secondary objectives were to determine differences in diet, sulfidogenic bacteria gene copy numbers (gcn) and hydrogen sulfide (H2S) levels between the 2 groups. Patients with AP were enrolled during hospitalization (n = 54). Patient residential addresses were geocoded, and the Centers for Disease Control and Prevention's SVI scores were appended. Dietary intake and serum H2S levels were determined. Microbial DNAs were isolated from stool, and gcn of sulfidogenic bacteria were determined. Minorities had higher SVI scores compared with NHWs ( P = 0.006). They also had lower consumption of beneficial nutrients such as omega-3 fatty acids [stearidonic ( P = 0.019), and eicosapentaenoic acid ( P = 0.042)], vitamin D ( P = 0.025), and protein from seafood ( P = 0.031). Lastly, minorities had higher pan-dissimilatory sulfite reductase A ( pan-dsrA ) gcn ( P = 0.033) but no significant differences in H2S levels ( P = 0.226). Minorities with AP have higher SVI compared with NHWs with AP. Higher SVI scores, lower consumption of beneficial nutrients, and increased gcn of pan-dsrA in minorities with AP suggest that neighborhood vulnerability could be contributing to AP inequities.

Gut Microecology May Be Involved in the Pathogenesis of Hashimoto Thyroiditis by Reducing Production of Hydrogen Sulfide.

Hashimoto thyroiditis (HT) is related to intestinal microbiota alteration, but the causal relationship remains unclear. Hydrogen sulfide (H2S) is a microbiota-derived metabolite. We speculated that abnormal intestinal microbiota might limit H2S production capacity, promoting HT pathogenesis. This work aimed to illustrate that the intestinal microbiota plays important roles in HT pathogenesis via microbiota-derived H2S levels. We collected feces from HT patients and healthy donors for fecal microbiota transplantation (FMT). Thirty-six female CBA/J mice were randomly assigned to 4 groups: experimental autoimmune thyroiditis (EAT) group, EAT + Healthy group, EAT + HT group, and EAT + HT + H2S group. 16S ribosomal RNA sequencing was performed to examine gut microbiota alterations and the H2S production pathway. Serum TgAb and H2S levels were assayed by enzyme-linked immunosorbent assay and H2S-selective sensors, respectively. T-cell subpopulations in the spleen were detected by flow cytometry. The gut microbiota was different after FMT among the EAT, EAT + Healthy, and EAT + HT groups. The thyroiditis score assessed by hematoxylin and eosin staining was higher in the EAT + HT group than that in the EAT and EAT + HT + H2S groups. Helper T (Th1) and Th17 cell differentiation ratios were increased in the EAT + HT group compared to the other 3 groups. Serum H2S levels were decreased and the dissimilatory sulfate reduction (DSR) pathway was attenuated in the EAT + HT group compared to the EAT + Healthy group. H2S alleviated thyroiditis severity and related immune disorders, which were aggravated by the FMT from HT patients. The attenuated DSR pathway in the gut microbiota from HT patients might be involved in thyroiditis pathogenesis.

Serum H2S as an indicator of exacerbation and pulmonary arterial hypertension in chronic obstructive pulmonary disease

Background and objective: Hydrogen sulfide (H2S) is a potential gasotransmitter produced by respiratory and vascular smooth muscle cells. Although some studies have examined H2S in chronic obstructive pulmonary disease (COPD), few have investigated its role in COPD exacerbations and pulmonary arterial hypertension (PAH). This study aimed to compare serum H2S levels between COPD patients and healthy controls, examine associations between H2S and COPD severity/exacerbations/PAH, and compare H2S levels between smokers and nonsmokers. Methods: Serum H2S was measured in 16 patients with stable COPD and 34 with acute exacerbations. COPD severity was classified using GOLD stages. Arterial blood gases, pulmonary arterial pressure by echocardiography, and clinical variables were assessed. Multivariable regression analyzed factors influencing H2S. ROC curves evaluated the diagnostic utility of H2S for exacerbations and PAH. Results: Serum H2S was lowest in GOLD stage IV patients compared to stages II and III. Levels were significantly lower in acute exacerbations versus stable COPD. COPD patients with PAH had lower H2S than those without. Arterial pH, FEV1, and FEV1/FVC positively associated with H2S, while PaCO2, severity, exacerbations, and PAH negatively influenced H2S. Optimal H2S cutoffs for indicating exacerbations and PAH were <46.7 μmol/L. Conclusions: Serum H2S may be a useful indicator of exacerbations and PAH in COPD patients.

Serum hydrogen sulphide levels in acute asthmatic children: a case control study

BackgroundIt’s thought that respiratory epithelium-produced reduced hydrogen sulphide (H2S) plays a role in the pathophysiology of acute asthma. In this case–control research, blood H2S levels were examined between matched acutely asthmatic children and non-asthmatic controls. The grade of acute asthma, vital signs and absolute eosinophilic count in the asthmatic children were likewise associated with the blood H2S level.MethodsForty Egyptian asthmatic children had visited the emergency room and forty age- and sex-matched non-asthmatic controls had their blood H2S levels measured using enzyme-linked immunosorbent assay (ELISA).ResultsThe serum H2S in the two groups did not differ statistically significantly. Serum H2S and respiratory rate showed a moderately significant inverse connection (r = -0.325, p = 0.041). However, serum H2S and other clinical or laboratory variables exhibited no meaningful relationships. Patients' absolute and percentage eosinophil counts were considerably higher than healthy controls. Serum H2S exhibited a sensitivity of 50% and a specificity of 32.5% for identifying children with acute asthma from non-asthmatic children.ConclusionChildren with asthma and those without asthma had similar serum H2S levels. It has a lousy relationship with respiratory rate. It is indicated that it is an inadequate screening and diagnostic tool since it has low sensitivity (50%) and specificity (32.5%) in differentiating acute asthmatic children.

Correlation between Serum H2S Level, Oxidative Stress, and Antioxidant Defence in Acute Coronary Syndrome

Correlation between Serum H2S Level, Oxidative Stress, and Antioxidant Defence in Acute Coronary Syndrome

Esculentoside A Alleviates Intestinal Dysmotility in Ulcerative Colitis by Regulating H2S/CSE and NO/nNOS Systems.

Background Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that commonly affects the health of many individuals. Esculentoside A (EsA), a saponin extracted from the roots of Phytolacca esculenta, has antioxidative and anti-inflammatory effects against various diseases. Nonetheless, its role in UC is undetermined. Hence, in this study, we examined the therapeutic effects of EsA in UC. Methods Primary intestinal neuronal cells (in vitro) were treated with lipopolysaccharide (LPS) to induce inflammatory injury. An in vivo UC rat model was created by the administration of dextran sulfate sodium (DSS) to rats, which were subsequently treated with different doses of EsA. The effects of EsA on intestinal motility, histological score, inflammatory response, hydrogen sulfide (H2S)/cystathionine γ-lyase (CSE) system, NO/neuronal nitric oxide synthase (nNOS) system, and LPS-induced primary intestinal neuronal cell viability loss, proliferation inhibition, and apoptosis were detected. Results In vitro, EsA treatment increased the number of DSS-inhibited bowel movements and body weight, improved the histological score of colitis, and inhibited the inflammatory response by reducing IL-6 and TNF-α levels in rats. More importantly, EsA reduced the NO and H2S levels in serum and CSE, CBS, and nNOS expressions in the colon tissue. In vivo, EsA treatment eased the viability loss, proliferation inhibition, and apoptosis of LPS-stimulated primary intestinal neuronal cells, as well as inhibited the expressions of IL-6, TNF-α, CSE, CBS, and nNOS in cells. Conclusion EsA improved intestinal motility and suppressed inflammatory response in DSS-induced UC, which may be mediated by H2S/CSE and NO/nNOS systems.

GYY4137 ameliorates sepsis-induced cardiomyopathy via NLRP3 pathway

Sepsis-induced cardiomyopathy (SICM) has a poor prognosis, with no effective therapeutic strategy currently. This study aimed to explore the mechanism underlying SICM and investigate the protective role of the hydrogen sulfide (H2S) donor GYY4137. This study included patients with SICM and animal models of SICM with wild-type and Nlrp3−/− mice, which were treated with or without GYY4137. Echocardiography, ELISA, TUNEL staining, and immunofluorescence were used to investigate phenotypic alterations. Serum levels of H2S and cytokines were measured. Inflammatory cell infiltration in the myocardial tissue was identified using immunohistochemistry and immunofluorescence. RNA expression profiles were identified using RNA sequencing. The protective mechanism of GYY4137 was further validated in the crosstalk between macrophages and cardiomyocytes using immunoblotting, real-time polymerase chain reaction (RT-PCR), and immunofluorescence when conditional medium of macrophages boosted by LPS were co-cultured with cardiomyocytes. Patients and animal models of SICM presented with lower serum H2S levels and heart dysfunction. GYY4137 reduced macrophage infiltration in septic heart tissue. GO analysis suggested that GYY4137 was involved in the inflammatory process. GYY4137 inhibited NLRP3 inflammasome activity in macrophages, reduced the secretion of inflammatory factors, and decreased the production of reactive oxygen species (ROS) in cardiomyocytes, thus exerting protective effects against SICM. We further found that the protective effects of GYY4137 were absent in Nlrp3-knockout models. GYY4137 ameliorates myocardial injury in SICM via the NLRP3 pathway by inhibiting the inflammatory response and reducing the production of myocardial ROS.

Differential effects of subchronic acrylonitrile exposure on hydrogen sulfide levels in rat blood, brain, and liver.

Hydrogen sulfide (H2S), as the third gasotransmitter participates in both cellular physiological and pathological processes, including chemical-induced injuries. We recently reported acute acrylonitrile (AN) treatment inhibited endogenous H2S biosynthesis pathway in rat and astrocyte models. However, there is still no evidence to address the correlation between endogenous H2S and sub-chronic AN exposure. This study aims to explore the modulatory effects of prolonged AN exposure on endogenous H2S levels and its biosynthetic enzymes in rat blood, brain and liver. A total of 50 male Sprague-Dawley rats were randomly divided into 5 groups, including the control group and AN-treated groups at dosages of 6.25, 12.5, 25 or 50 mg/kg. Rats received one exposure/day, 5 days/week, for 4 consecutive weeks. The rat bodyweight and brain/liver organ coefficient were detected, along with liver cytochrome P450 2E1(CYP2E1) expression. In addition, the H2S contents in rat serum and plasma, and in cerebral cortex and liver tissues were measured by methylene blue method. The expression of H2S-generating enzymes, including cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MPST) was also measured with Western blot both in rat cerebral cortex and liver. Subchronic exposure to AN significantly inhibited bodyweight-gain and increased the liver CYP2E1 expression compared with the control. In addition, AN significantly increased H2S levels in rat plasma and serum, but not in liver. The endogenous H2S level in rat cerebral cortex was also significantly increased upon AN treatment, when expression of the major H2S-generating enzymes, CBS and 3-MPST were significantly enhanced. However, hepatic protein levels of CBS and CSE were significantly increased, whereas hepatic levels of 3-MPST were significantly decreased. This study showed that sub-chronic AN exposure increased endogenous H2S contents in rat blood and brain tissues, but not liver, which may be resulted from the distinct expression profile of H2S-producing enzymes in response to AN. The blood H2S contents may be applied as a potential novel biomarker for surveillance of chronically AN-exposed populations. Subchronic intraperitoneal exposure to acrylonitrile increased H2S content in rat blood and cerebral cortex, but not in liver.Distinct tissue expression profiles of H2S-producing enzymes contribute to the acrylonitrile-induced differential effects on the H2S level.Blood H2S level may be a biomarker for subchronic exposure to acrylonitrile.

Association between serum hydrogen sulfide concentrations and dysglycemia: a population-based study

Background and aimHydrogen sulfide (H2S), a signaling gasotransmitter, is involved in carbohydrate metabolism. Here, we aimed to assess the potential association between serum H2S and dysglycemia in the framework of a population-based study.MethodsAdults men and women with completed data (n = 798), who participated in the Tehran Lipid and Glucose Study (2014–2017) were included in the study. Medians of fasting serum H2S concentration were compared across the glycemic status of the participants, defined as type 2 diabetes mellitus (T2DM), isolated impaired fasting glucose (IIFG), isolated impaired glucose tolerance (IIGT), combined IFG-IGT, and normal glycemia [i.e., those with both normal fasting glucose (NFG) and normal glucose tolerance (NGT)]. Multinomial logistic regression was used to assess potential associations between serum H2S and the defined glycemic status.ResultsMean age of the participants was 45.1 ± 14.0 y, and 48.1% were men. Prevalence of T2DM, IIFG, IIGT, and combined IFG-IGT was 13.9, 9.1, 8.1, and 4.8% respectively. No significant difference was observed in serum H2S concentrations between the groups. Lower serum H2S (< 39.6 µmol/L) was associated with an increased chance of having IIGT (OR = 1.96, 95% CI = 1.15–3.34) in the adjusted model.ConclusionReduced serum H2S level may be associated with impaired glucose tolerance.

Reduced Levels of H2S in Diabetes-Associated Osteoarthritis Are Linked to Hyperglycaemia, Nrf-2/HO-1 Signalling Downregulation and Chondrocyte Dysfunction.

Different findings indicate that type 2 diabetes is an independent risk factor for osteoarthritis (OA). However, the mechanisms underlying the connection between both diseases remain unclear. Changes in the balance of hydrogen sulphide (H2S) are thought to play an important role in the pathogenesis of diabetes and its complications, although its role is still controversial. In this study, we examined the modulation of H2S levels in serum and chondrocytes from OA diabetic (DB) and non-diabetic (non-DB) patients and in cells under glucose stress, in order to elucidate whether impairment in H2S-mediated signalling could participate in the onset of DB-related OA. Here, we identified a reduction in H2S synthesis in the cartilage from OA-DB patients and in cells under glucose stress, which is associated with hyperglycaemia-mediated dysregulation of chondrocyte metabolism. In addition, our results indicate that H2S is an inductor of the Nrf-2/HO-1 signalling pathway in cartilage, but is also a downstream target of Nrf-2 transcriptional activity. Thereby, impairment of the H2S/Nrf-2 axis under glucose stress or DB triggers chondrocyte catabolic responses, favouring the disruption of cartilage homeostasis that characterizes OA pathology. Finally, our findings highlight the benefits of the use of exogeneous sources of H2S in the treatment of DB-OA patients, and warrant future clinical studies.

Hydrogen Sulfide Promotes Thyroid Hormone Synthesis and Secretion by Upregulating Sirtuin-1.

Objective: One mechanism of hypothyroidism involves the disruption of thyroid hormone synthesis and secretion by thyrocytes. Hydrogen sulfide (H2S), as a gas signaling molecule, participates in many physiopathologic processes by upregulating sirtuin-1 (SIRT1). The aim of the current study was to explore whether H2S promotes the synthesis and secretion of thyroid hormones by upregulating SIRT1. Methods: Real-time PCR and immunohistochemistry were used to detect the mRNA and protein expression of H2S-generating enzymes in normal human thyroid tissues. Serum H2S concentrations from hypothyroid patients (n = 32) and euthyroid participants (n = 41) were detected by H2S-selective sensors. Thirty-one Sprague–Dawley rats were divided into control group (n = 10), hypothyroid group (induced by MMI, n = 10) and hypothyroid + NaHS group (n = 11), and the FT4, TT4 and TSH levels were assayed. Human primary thyrocytes were incubated with H2S donor sodium hydrosulfide (NaHS) or NaHS plus SIRT1 inhibitor (EX527) in vitro. Thyroid hormone synthesis- and secretion-related proteins [thyroid peroxidase (TPO), sodium iodide transporter (NIS), Pendrin, monocarboxylic acid transporter 8 (MCT8)] were analyzed by real-time PCR and Western blot. Results: H2S levels in serum from hypothyroid patients were decreased compared to those from euthyroid participants (p < .05), and serum H2S levels were positively correlated with FT3, FT4, TT3, and TT4 levels in all subjects (all p < .0001). In vivo, NaHS promoted thyroid function in hypothyroid rats (p < .05). In vitro, H2S was detected in supernatant, and CBS mRNA was higher than CSE and 3-MPST in human primary thyrocytes (p < .05). The protein levels of TPO, NIS, Pendrin and MCT8 were upregulated in a concentration-dependent manner for NaHS in thyrocytes. After blocking SIRT1 with EX527, we found that the increasing levels of TPO, NIS, Pendrin, and MCT8 and TPO activity were downregulated in thyrocytes incubated with NaHS, and FT4 levels in the cell supernatant were also decreased significantly (all p < .05). Conclusion: H2S is mainly generated in thyrocytes by CBS. Serum H2S levels are decreased with hypothyroidism. H2S promotes the synthesis and secretion of thyroid hormones and the expression of related molecules by upregulating SIRT1.

Inhibition of HDACs (Histone Deacetylases) Ameliorates High-Fat Diet-Induced Hypertension Through Restoration of the MsrA (Methionine Sulfoxide Reductase A)/Hydrogen Sulfide Axis.

[Figure: see text].

A Study on Serum Nitric Oxide and Hydrogen Sulfide in Essential Hypertension Cases in a Tertiary Care Hospital in West Bengal

Background-Essential hypertension is a multifactorial disease of unknown etiology characterized by a chronic elevation of blood pressure without any secondary causes. Nitric oxide and hydrogen sulfide are vasodilatory gasotransmitters whose deficiency results in endothelial dysfunction and vasoconstriction and hence is one of the etiological factors in the development of hypertension. Aims and Objectives – The study aimed to estimate the serum levels of NO and H₂S and to find out their correlation in essential hypertension cases and normotensive controls. Materials and Methods- Serum levels of NO and H₂S were measured using chemical methods, in fifty patients with essential hypertension and compared with fifty age-matched controls. Results- The mean serum NOx level in essential hypertension cases is 45.45 ± 11.09 µmol/L which is significantly lower (p-value &lt;0.001) than that of controls where it is 166.40 ± 16.63 µmol / L. The mean serum H₂S level in essential hypertension cases is 45.61 ± 11.01 µmol/ L which is again significantly lower ( p-value &lt;0.001) than controls in which it is 111.54 ± 9.60 µmol/ L. A statistically significant positive correlation exists between serum NOx and H₂S levels in overall study subjects. Conclusion- This study demonstrates that both the serum levels of NO and H₂S decrease with an increase in BP in essential hypertension cases. There exists a positive correlation between NO and H₂S in overall study subjects. Thus, the simultaneous decline in bioavailability of both NO and H₂S is a significant underlying cause in the development of essential hypertension.

Association of Hydrogen Sulfide with Femoral Bone Mineral Density in Osteoporosis Patients: A Preliminary Study.

BackgroundAccumulated evidence has suggested that hydrogen sulfide (H2S) has a role in bone formation and bone tissue regeneration. However, it is unknown whether the H2S content is associated with bone mineral density (BMD) in patients with osteopenia/osteoporosis.Material/MethodsIn the present study, we aimed to explore the changes of serum H2S in osteopenia and osteoporosis patients. We analyzed femur expression of cystathionine β synthase (CBS), cystathionine γ lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), which are key enzymes for generating H2S.ResultsSixteen (16%) patients had osteopenia, 9 (9%) had osteoporosis, and 75 (75%) had normal BMD. In comparison with patients with normal BMD (controls), the serum levels of H2S were unexpectedly increased in patients with osteopenia and osteoporosis. This increase was much higher in patients with osteoporosis than in those with osteopenia. Serum H2S levels were negatively correlated with femoral BMD, but not lumbar BMD. Interestingly, the expression of CBS and CSE were downregulated in femur tissues in patients with osteoporosis, whereas the expression of 3-MST remained unchanged. Serum phosphorus levels, alkaline phosphatase, hemoglobin, and triglycerides were found to be closely associated with CBS and CSE scores in femur tissues.ConclusionsSerum H2S levels and femur CBS and CSE expression may be involved in osteoporosis pathogenesis.

Association between hydrogen sulfide and OSA-associated hypertension: a clinical study.

We sought to unravel the role of hydrogen sulfide (H2S) in the development of hypertension in patients with obstructive sleep apnea (OSA). The study sample included 80 patients with OSA and 45 healthy controls. All subjects underwent measurement of blood pressure (BP) and serum H2S level in the morning. Twentynine of the 39 patients with OSA and concomitant hypertension and 23 of the 41 patients with OSA but no concomitant hypertension received continuous positive alveolar pressure (CPAP) therapy for 4 weeks. Twenty-four-hour ambulatory BP and serum H2S were determined before and after CPAP. Respiratory indices including apnea hypopnea index (AHI), lowest oxygen saturation (SaO2), and length of time < 90% saturated (T90) were determined by polysomnography. Associations between H2S, BP, respiratory indices, and changes with CPAP were analyzed. OSA patients had significantly higher systolic BP (p = 0.003) and diastolic BP (p = 0.009) and lower H2S levels (p = 0.02) compared to healthy controls. H2S negatively correlated with AHI (p = 0.005), T90 (p = 0.009), morning systolic BP (p = 0.02), and morning diastolic BP (p = 0.03). All respiratory indices were significantly improved (p < 0.05) after CPAP in OSA patients with or without hypertension. BP was significantly reduced and H2S significantly increased after CPAP in OSA patients with hypertension (p < 0.05) but not in OSA patients without hypertension (p > 0.05). Multivariate linear regression analysis demonstrated that 24h systolic BP and 24h diastolic BP correlated with H2S as well as their changes after CPAP treatment. Reduction in H2S may play a role in the pathogenesis of hypertension in patients with OSA.

Association of serum hydrogen sulphide with hypertension and proteinuria in pre-eclampsia

Background: Preeclampsia is a hypertensive disorder of pregnancy affecting multiple systems and characterized chiefly by hypertension and proteinuria in a previously normotensive and non proteinuric women. The main underlying cause for its pathophysiology is an imbalance between the physiological vasoconstrictor and vasodilator molecules in circulation leading to maternal endothelial dysfunction. Hydrogen sulphide (H2S) is a physiological vasodilatory gasotransmitter which plays an important role in the development of hypertension and proteinuria in preeclampsia.&#x0D; Aims and Objectives: The aim of this study was to determine the serum level of hydrogen sulphide and spot urinary protein levels in preeclampsia cases and compare it with age matched controls which were normal pregnant women and to find any correlation, if exists, between these two parameters.&#x0D; Materials and Methods: Serum level of H2S and spot urinary protein level were measured in one hundred pregnant women with preeclampsia and the values were compared with age matched controls.&#x0D; Results: The mean serum H2S level was 32.31 ± 12.62μmol/L in patients which was significantly lower (p&lt;0.001) when compared to controls where mean was 114.50 ±20.35μmol/L. The mean spot urinary protein level was found to be 11.83 ± 5.06 mg/dl in preeclampsia cases which was significantly higher (p&lt;0.001) than in controls where it was 7.18 ± 2.38 mg/dl. A negative correlation was found between the serum level of H2S and both the systolic BP (r=-0.725, p&lt;0.001) and diastolic BP (r= - 0.639, p&lt;0.001) in preeclampsia patients.A negative correlation was also observed between the serum levels of H2S and spot urinary protein in preeclampsia (r=-0.541, p&lt;0.001).&#x0D; Conclusion: The present study has elucidated that the serum levels of hydrogen sulphide decreases and the spot urinary protein levels increases in preeclampsia when compared to normal pregnant women and hydrogen sulphide shows a negative correlation with both systolic and diastolic BP in preeclampsia. This study also demonstrates that,there exists a negative correlation between the serum H2S level and spot urinary protein level in preeclampsia patients.

Effect of hydrogen sulfide on the intimal hyperplasia of vein grafts in rabbits

Objective To observe the effect of exogenous hydrogen sulfide (H2S) on the intimal hyperplasia of vein grafts in rabbits and and its possible molecular mechanism. Methods Forty New Zealand rabbits were randomly divided into 5 group, including blank control group (Ctr group); two weeks of simple transplantation; four weeks of simple transplantation; transplantation + NaHS 2 weeks group (NaHS: 30 μmol/kg. 3 days, 2 weeks of continuous administration), transplantation + NaHS 4 weeks group (NaHS: 30 μmol/kg. 3 days, 4 weeks of continuous administration). Rabbit jugular vein transplantation animal model was established. Administration by intraperitoneal injection once 3 days. Serum H2S level was detected by enzyme linked immunosorbent assay (ELISA). The structure and hyperplasia of vascular tissue were observed by hematoxylin-eosin staining (HE) staining. real-time quantitative polymerase chain reaction (Real-time PCR) was used to determine the expression levels of cystathionine-gamma-lyase (CSE) mRNA. CSE, Calmodulin (p-CaM/ CaM)and Cyclin D1 protein levels were measured by Western blotting. Results After NaHS treatment, the intimal hyperplasia of vein grafts was relieved. Compared with the corresponding group, the serum H2S level increased in the transplantation + NaHS 2 weeks group and transplantation + NaHS 4weeks group (33.65±4.10 vs. 23.56±4.82, P<0.05; 36.50±4.62 vs. 23.72±3.95, P<0.05). And the expression of CSE mRNA and protein increased significantly (mRNA: 0.54±0.04 vs. 0.15±0.05, P<0.05; 1.08±0.13 vs. 0.11±0.02, P<0.05; Protein: 0.56±0.06 vs. 0.47±0.03, P<0.05; 1.14±0.07 vs. 0.38±0.04, P<0.05). The expression of p-CaM/CaM and Cyclin D1 protein decreased significantly (p-CaM: 0.25±0.05 vs. 0.52±0.06, P<0.05; 1.21±0.09 vs. 2.39±0.15, P<0.05; CaM: 0.42±0.04 vs. 0.73±0.07, P<0.05, 0.47±0.05 vs. 1.17±0.06 P<0.05; Cyclin D1: 0.28±0.06 vs. 0.95±0.11, P<0.05; 0.29±0.04 vs. 1.02±0.10, P<0.05). Conclusion Exogenous hydrogen sulfide could inhibit the intima proliferation of vein grafts which related to the reduction of the expression of p-CaM/CaM and Cyclin D1. Key words: Hydrogen sulfide; Vein grafts; Transplantation; Intima hyperplasia

Association between Serum Levels of Nitric Oxide and Hydrogen Sulfide in Pre-eclampsia

Background: Preeclampsia is a multisystem disorder that is characterized by hypertension and proteinuria in women with no history of hypertension and proteinuria. It is mainly caused due to an imbalance between the physiological vasoconstrictor and vasodilator molecules. Nitric oxide and hydrogen sulphide are well established vasodilatory endogenous gasotransmitters that exhibit reduced production from intrauterine tissues during preeclampsia. Aims and objectives: The aim of the study was to determine the serum levels of nitric oxide and hydrogen sulfide in preeclampsia cases compared with age matched controls and to rule out, whether there is a significant relationship if any, between these two gasotransmitters in preeclampsia. Materials and methods: Serum levels of NOx and H2S were measured in 100 pregnant women with preeclampsia and the values were matched with controls. Results: The mean serum NOx levels of preeclamptic patients was 45.88 ± 17.72 µmol/L which were significantly lower (p<0.001) than those observed in control with a values of 161.09 ± 27.46 µmol/L. The mean serum H2S level was 32.31 ± 12.62 µmol/L in patients which was significantly lower (p<0.001) when compared to control where mean we observed 114.50 ± 20.35 µmol/L. A positive correlation exists between serum NOx and H2S levels in preeclampsia (r=0.691, p<0.001). Conclusion: The present study has elucidated that the serum levels of nitric oxide and hydrogen sulfide decrease in preeclampsia compared to normal pregnant women and these two molecules show a positive correlation in their levels in preeclampsia.

Alpha-lipoic acid regulates the autophagy of vascular smooth muscle cells in diabetes by elevating hydrogen sulfide level

Dysfunctional vascular smooth muscle (VSM) plays a vital role in the process of atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Alpha-lipoic acid (ALA) can prevent the altered VSM induced by diabetes. However, the precise mechanism underlying the beneficial effect of ALA is not well understood. This study aimed to determine whether ALA ameliorates VSM function by elevating hydrogen sulfide (H2S) level in diabetes and whether this effect is associated with regulation of autophagy of VSM cells (VSMCs). We found decreased serum H2S levels in Chinese patients and rats with type 2 diabetes mellitus (T2DM). ALA treatment could increase H2S level, which reduced the autophagy-related index and activation of the 5′-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, thereby protecting vascular function in rats with T2DM. Propargylglycine (PPG), a cystathionine-γ-lyase inhibitor, could weaken the ALA effect. In cultured VSMCs, high glucose level also reduced H2S level, upregulated the autophagy-related index and activated the AMPK/mTOR pathway, which were reversed by concomitant application of sodium hydrosulfide (NaHS, an H2S donor) or ALA. The protective effect of NaHS or ALA was attenuated by rapamycin (an autophagy activator), 5-amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide (an AMPK activator) or PPG. In contrast, Compound C (an AMPK inhibitor) enhanced the effect of ALA or NaHS. ALA may have a protective effect on VSMCs in T2DM by elevating H2S level and downregulating autophagy via the AMPK/mTOR pathway. This study provides a new target for addressing diabetic macroangiopathy.