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Acute Kidney Injury (AKI) is frequently observed in hospitalized patients in intensive care units, often caused by renal ischemia-reperfusion injury (IRI). IRI disrupts the function of various 'remote organs' such as the lungs, pancreas, intestine, liver, heart, and brain through inflammation, oxidative stress, apoptosis, leukocyte infiltration, and increased urea and creatinine levels. Gender differences in renal IRI-induced injury are noted. H2S, an endogenous gaseous modulator, shows potential in vasodilation, bronchodilation, and hypotension and can regulate apoptosis, inflammation, angiogenesis, metabolism, and oxidative stress. This study aims to investigate the protective effects of NaHS on brain, heart, and lung injuries following renal IR and to assess the oxidative system status as a potential mechanism in male and female rats. Forty-eight Wistar rats were randomly divided into eight groups (n = 6): Control/Saline, Sham/Saline, IR/Saline, and IR/NaHS in both sexes. Forty-five minutes of bilateral renal ischemia followed by 24-hour reperfusion was induced in the IR groups. NaHS (100µM/Kg, IP) was administered 10 min before clamp release in treated groups. BUN, SCr, BUN/SCr, albuminuria, histopathology, and oxidative stress biomarkers of the brain, heart, and lung were assessed as remote organs. IR increased serum markers of renal function, albuminuria, malondialdehyde levels, and tissue injury scores while reducing nitrite levels and superoxide dismutase and glutathione peroxidase activities. NaHS treatment reversed the adverse effects of IR in remote organs in both sexes, although it showed limited improvement in renal function. Our findings demonstrate that NaHS has a beneficial effect on remote organ injury following renal IR by mitigating oxidative stress, with noted tissue-specific and gender-specific differences in response. These findings suggest NaHS as a potential therapeutic agent for mitigating multi-organ injury after renal IR, with effects varying by tissue and gender. [ABSTRACT FROM AUTHOR]

Abstract Acute Kidney Injury (AKI) is frequently observed in hospitalized patients in intensive care units, often caused by renal ischemia-reperfusion injury (IRI). IRI disrupts the function of various ‘remote organs’ such as the lungs, pancreas, intestine, liver, heart, and brain through inflammation, oxidative stress, apoptosis, leukocyte infiltration, and increased urea and creatinine levels. Gender differences in renal IRI-induced injury are noted. H2S, an endogenous gaseous modulator, shows potential in vasodilation, bronchodilation, and hypotension and can regulate apoptosis, inflammation, angiogenesis, metabolism, and oxidative stress. This study aims to investigate the protective effects of NaHS on brain, heart, and lung injuries following renal IR and to assess the oxidative system status as a potential mechanism in male and female rats. Forty-eight Wistar rats were randomly divided into eight groups (n = 6): Control/Saline, Sham/Saline, IR/Saline, and IR/NaHS in both sexes. Forty-five minutes of bilateral renal ischemia followed by 24-hour reperfusion was induced in the IR groups. NaHS (100µM/Kg, IP) was administered 10 min before clamp release in treated groups. BUN, SCr, BUN/SCr, albuminuria, histopathology, and oxidative stress biomarkers of the brain, heart, and lung were assessed as remote organs. IR increased serum markers of renal function, albuminuria, malondialdehyde levels, and tissue injury scores while reducing nitrite levels and superoxide dismutase and glutathione peroxidase activities. NaHS treatment reversed the adverse effects of IR in remote organs in both sexes, although it showed limited improvement in renal function. Our findings demonstrate that NaHS has a beneficial effect on remote organ injury following renal IR by mitigating oxidative stress, with noted tissue-specific and gender-specific differences in response. These findings suggest NaHS as a potential therapeutic agent for mitigating multi-organ injury after renal IR, with effects varying by tissue and gender.

AIM: To investigate the effects of sodium hydrosulfide (NaHS) on hexokinase 2 (HK2)-nucleo-tide-binding oligomerization domain-like receptor protein 3 (NLRP3)-gasdermin D (GSDMD) pathway and pyroptosis induced by lung ischemia/reperfusion (I/R) in rats. METHODS: Male Sprague-Dawley rats were divided into 6 groups: control group, control+NaHS group, I/R group, low-dose NaHS+I/R (L+I/R) group, medium-dose NaHS+I/R (M+I/R) group, and high-dose NaHS+I/R (H+I/R) group, with 6 rats in each group. The NaHS was administered via intraperitoneal injection at 1.5 mL, 30 min before modeling. The left lung tissues were collected 30 min after ischemia and 1 h after reperfusion, and the wet/dry weight ratio and total lung water content were recorded. Hematoxylin-eosin (HE) staining was used to examine lung tissue morphological changes. The levels of malondialdehyde (MDA), myeloper oxidase (MPO) and lactate in lung tissues were measured with test kits. ELISA was employed to determine the levels of interleukin-1p (IL-1p) and IL-18. The expression of glycolysis- and pyroptosis-related indicators was analyzed by Western blot, qRT-PCR and immunofluorescence staining. RESULTS: Compared with control group, the rats in NaHS group showed no significant differences in all laboratory tests (P>0. 05). The rats in I/R group exhibited significant lung injury, oxidative stress, increased lactate level, and up-regulated glycolysis and pyroptosis (P<0. 05 or P<0. 01). Compared with I/R group, the indicators in L+I/R group showed a downward trend (P<0. 01) or no difference (P>0. 05), while those in M+I/R group displayed a significant reduction (P<0. 05 or P<0. 01). However, the indexes in H+I/R group exhibited no significant differences in these tests (all P>0. 05). CONCLUSION: A moderate dose (56 xmol"L-1-kg-1) of NaHS mitigated the occurrence of pyroptosis by inhibiting the HK2-NLRP3-GSDMD pathway, thus contributing to the attenuation of lung I/R injury in rats. [ABSTRACT FROM AUTHOR]

In recent years, the cardiotoxicity and hepatotoxicity induced by chemotherapeutic drugs such as cisplatin (CP) have become significant issues. The current research looks into the effects of sodium hydrosulfide (NaHS) on CP-induced hepatotoxicity and cardiotoxicity in rats. A total of 32 male Sprague Dawley rats were separated into four different groups: (1) control group, received only normal saline; (2) NaHS group, was intraperitoneally injected with NaHS (200 µg/kg/d, dissolved in saline) for 15 days; (3) CP group, was intraperitoneally injected only one dose of CP (5 mg/kg) and (4) CP plus NaHS group, received CP along with NaHS. Blood and tissues samples were harvested for biochemical, histopathological, and immunohistochemical investigations. To determine the data's statistical significance, a one-way analysis of variance was used. CP injection significantly increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), Creatine phospho kinase (CK-MB), cholesterol, low-density lipoprotein (LDL), triglyceride (TG), and lipid peroxidation levels, while high-density lipoprotein (HDL), albumin, glutathione peroxidase, superoxide dismutase, and catalase (CAT) levels were significantly reduced with pathological alterations in liver and heart tissues. Co-treatment NaHS with CP ameliorates the biochemical and histological parameters. Also, Treatment solely with CP resulted in increased tissue expression of interleukin-1β (IL-1β) in liver and heart but co-treatment NaHS with CP reduced the expression of this inflammatory factor. We conclude that NaHS operates in the liver and heart as an anti-inflammatory and powerful free radicals' scavenger to inhibit the toxic effects of CP, both at the biochemical and histopathological levels. NaHS protects the liver and heart against Cisplatin-induced toxicity [ABSTRACT FROM AUTHOR]

Objective To investigate the function of sodium hydrosulfide (NaHS) to regulate mitochondrial fusion/fission in diabetic cardiomyopathy and underlying mechanism. Methods Db/db mice as type 2 diabetes animal model were treated by NaHS. H9C2 cells incubated with glucose (40 mmol/L), palmitic acid (200 μmol/L, Pal) and oleate (200 μmol/L, Ole) were intervened by NaHS (100 μmol/L). H2C9 cells were divided into control, HG+Pal+Ole, HG+Pal+Ole+NaHS and Pal+Ole+DJ-1 siRNA+NaHS groups. The protein level of Mfn2, Fis1, CSE, and DJ-1 was determined by Western blot. Mitotracker staining was used to observe the morphology of mitochondria. The ultra-structural alteration of cardiac tissues was detected by transmission electron microscopy. The cardiac functions were detected by echocardiography. Results Expression of Fis1 was increased (P＜0.05) and expression of Mfn2 was decreased (P＜0.05) in db/db and H9C2 treated by HG+Pal+Ole compared to control group. NaHS could upregulate the expression DJ-1, enhance the expression of Mfn2, and reduce the expression of Fis1. In db/db mice, cardiac systolic function was reduced. Disordered arrangement of myofilament, loss of cristae and mitochondrial fission were observed. NaHS could ameliorate these alterations. Conclusions NaHS may alleviate mitochondria injury by promoting mitochondrial fusion.

The comprehensive recovery of copper and arsenic from black copper slime by oxidation leaching method was studied. The effects of acidity, hydrogen peroxide content, temperature, leaching time and liquid volume to solid mass ratio on the leaching rate of copper and arsenic were investigated. The results show that under the conditions of acidity of 200 g/L, hydrogen peroxide content of 30%, temperature of 80 °C bleaching time of 2. 0 h, liquid volume to solid mass ratio of 9 : 1, the leaching rates of copper and arsenic can reach 99. 53% and 98. 24 %, respectively. After oxidative acid leaching, sodium hydrosulfide is added into the solution at the rate of n(NaHS)/n(Cu) = 1. 1 to precipitate copper. The mass concentration of copper in the solution after copper and arsenic separation is lower than 0. 01 g/L, and the mass concentration of arsenic is greater than 40 g/L. The copper and arsenic are effectively separated. Arsenic-rich liquid can be reduced with sulfur dioxide, and arsenic trioxide and reduced liquid can be returned to the oxidation leaching process. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the potential neuroprotective effects of sodium hydrosulfide (NaHS) as an H2S donor on spatial learning and memory in the streptoztocin (STZ) rat model of Alzheimer’s disease. Methods: The animals were divided into the following groups: Control, NaHS (2.8 mg/kg per day), and Alzheimer's disease (AD) groups, which included STZ, STZ+saline, and STZ+NaHS. The last three groups consisted of Alzheimer's rats that were administered either saline or NaHS at doses of 2.8 and 5.6 mg/kg per day for a duration of 10 days. To induce AD, STZ at a dose of 3 mg/kg (10 μl per injection site) was administered into the lateral ventricles. All rats underwent training in the Morris water maze. Results: Our results showed that the intraventricular injection of STZ resulted in a significant increase in both the time taken and distance traveled to reach the platform compared to the control group. The memory deficits induced by STZ were mitigated by the administration of sodium hydrosulfide, leading to a decrease in the time and distance needed to reach the platform. Additionally, in the probe test, the percentage of time spent and distance traveled in the target quadrant was significantly higher in the group treated with sodium hydrosulfide group compared to the saline-treated STZ group. Conclusion: Sodium hydrosulfide was found to enhance learning and memory in AD rats. These findings indicate that sodium hydrosulfide treatment may be beneficial for addressing cognitive deficits in AD. [ABSTRACT FROM AUTHOR]

To investigate the function of sodium hydrosulfide (NaHS) to regulate mitochondrial fusion/fission in diabetic cardiomyopathy and underlying mechanism. Methods Dh/db mice as type 2 diabetes animal model were treated by NaHS. H9C2 cells incubated with glucose (40 mmol/L), palmitic acid (200 µmol/L, Pal) and oleate (200 µmol/L, Ole) were intervened by NaHS (100 µmol/L). H2C9 cells were divided into control, HG+Pal+Ole, HG+Pal+Ole+NaHS and Pal+Ole+DJ-1 siRNA+NaHS groups. The protein level of Mfn2, Fis1, CSE, and DJ-1 was determined by Western blot. Mitotracker staining was used to observe the morphology of mitochondria. The ultra-structural alteration of cardiac tissues was detected by transmission electron microscopy. The cardiac functions were detected by echocardiography. Results Expression of Fis1 was increased (P<0.05) and expression of Mfn2 was decreased (P<0.05) in db/db and H9C2 treated by HG+Pal +Ole compared to control group. NaHS could upregulate the expression DJ-1, enhance the expression of Mfn2. and reduce the expression of Fis1. In db/dh mice, cardiac systolic function was reduced. Disordered arrangement of myofilament, loss of cristae and mitochondrial fission were observed. NaHS could ameliorate these alterations. Conclusions NaHS may alleviate mitochondria injury by promoting mitochondrial fusion. [ABSTRACT FROM AUTHOR]

Strigolactones (SLs) and hydrogen sulfide (H2S) have both been shown to play important roles in plant growth, development, and environmental adaption. At present, there was no reported on the mechanism by which SLs might participate in H2S-induced salt tolerance. In this study, tomato (Solanum lycopersicum L. ‘Micro-Tom’) was used to investigate the role of SLs and H2S and their relationship under salt stress. Our results show that 25 µM H2S donor sodium hydrosulfide (NaHS) and 15 µM SLs synthetic analogue GR24 significantly promoted tomato seedling growth under salt stress. TIS108 (3 µM, a SLs synthesis inhibitor) and hypotaurine (HT, 300 µM, a H2S scavenger) inhibited the positive role of NaHS and GR24 under salt stress, respectively. Meanwhile, NaHS treatment significantly increased endogenous SL content, the activity of SL synthesis-related enzymes CCD7 and CCD8, and the expression of SL synthesis-related genes (SlD27, SlD14, SlMAX1, and SlMAX2) under salt stress. Further, after silencing a SL synthesis-related gene SlD27, the relieving role of NaHS in salt stress was basically eliminated. Silencing of SlD27 decreased endogenous SL content, while NaHS did not enhance the endogenous SL content in SlD27-silencing seedling. Therefore, H2S might enhance salt tolerance in tomato seedlings by up-regulating the expression of SL synthesis-related gene SlD27.

In higher plants, hydrogen sulfide (H2S) is a recognized signaling molecule that performs multiple regulatory functions. The enzyme L-cysteine desulfhydrase (LCD) catalyzes the conversion of L-cysteine (L-Cys) to pyruvate and ammonium with the concomitant generation of H₂S, and it is considered one of the main sources of H2S in plants. Using non-denaturing polyacrylamide gel electrophoresis (PAGE) in combination with a specific assay for LCD activity, this study aims to identify the potential LCD isozymes in wild-type Arabidopsis thaliana seedlings of 16 days old grown under in vitro conditions, and to evaluate the potential impact of nitric oxide (NO) and H2S on these LCD isozymes. For this purpose, an Atnoa1 mutant characterized to have a low endogenous NO content as well as the exogenous application of H2S were used. Five LCD isozymes were detected, with LCD IV being the isozyme that has the highest activity. However, the LCD V activity was the only one that was positively modulated in the Atnoa1 mutants and by exogenous H2S. To our knowledge, this is the first report showing the different LCD isozymes present in Arabidopsis seedlings and how their activity is affected by NO and H2S content.

In higher plants, hydrogen sulfide (H2S) is a recognized signaling molecule that performs multiple regulatory functions. The enzyme L-cysteine desulfhydrase (LCD) catalyzes the conversion of L-cysteine (L-Cys) to pyruvate and ammonium with the concomitant generation of H₂S, and it is considered one of the main sources of H2S in plants. Using non-denaturing polyacrylamide gel electrophoresis (PAGE) in combination with a specific assay for LCD activity, this study aims to identify the potential LCD isozymes in wild-type Arabidopsis thaliana seedlings of 16 days old grown under in vitro conditions, and to evaluate the potential impact of nitric oxide (NO) and H2S on these LCD isozymes. For this purpose, an Atnoa1 mutant characterized to have a low endogenous NO content as well as the exogenous application of H2S were used. Five LCD isozymes were detected, with LCD IV being the isozyme that has the highest activity. However, the LCD V activity was the only one that was positively modulated in the Atnoa1 mutants and by exogenous H2S. To our knowledge, this is the first report showing the different LCD isozymes present in Arabidopsis seedlings and how their activity is affected by NO and H2S content. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide can induce myocardial cell injury, which has been widely used in the preparation of septic cardiomyopathy models. We herein aimed to evaluate the protective effects of sodium hydrosulfide against oxidative stress and endoplasmic reticulum stress on the cell model of septic cardiomyopathy and to explore whether the protein kinase RNA-like endoplasmic reticulum kinase-eukaryotic initiation factor 2 alpha signaling pathways was involved. The sepsis induced cardiomyopathy model which was established by inducing rat cardiomyoblast cell line H9c2 cells with lipopolysaccharide and sodium hydrosulfide and endogenous hydrogen sulfide inhibitor (DL-propargylglycine) were used for intervention treatment. Then, cell viability, endogenous hydrogen sulfide levels, lactate dehydrogenase, reactive oxygen species, superoxide dismutase, glutathione and malondialdehyde were determined using commercial assay kits; enzyme-linked immunosorbent assay was used to determine creatine kinase-myoglobin binding, interleukin-6, tumor necrosis factor alpha and interleukin-10; reverse transcription-polymerase chain reaction was used to determine cystathionine gamma-lyase messenger RNA expression; and Western blot was used to determine glucose-regulated protein 78, protein kinase RNA-like endoplasmic reticulum kinase, phosphorylated protein kinase RNA-like endoplasmic reticulum kinase, eukaryotic initiation factor alpha, phosphorylated eukaryotic initiation factor alpha, activating transcription factor 4 and C/EBP-homologous protein levels. Sodium hydrosulfide increased the hydrogen sulfide contents of cells, but did not affect the messenger RNA expression of cystathionine gamma-lyase. It attenuated the decrease in cell viability caused by lipopolysaccharide; reduced the release of the myocardial enzymes like lactate dehydrogenase and creatine kinase-myoglobin binding; reduced the level of inflammatory factors like interleukin-6 and tumor necrosis factor alpha; reduced the level of oxidative stress; inhibited the expression of protein kinase RNA-like endoplasmic reticulum kinase pathway proteins. Sodium hydrosulfide treatment improves septic cardiomyopathy by inhibiting oxidative stress and endoplasmic reticulum stress via the protein kinase RNA-like endoplasmic reticulum kinase-eukaryotic initiation factor alpha pathway, which may be a theory for the treatment of septic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Gaseous molecules hydrogen sulfide (H2S) and salicylic acid (SA) enhance plant acclimation to environmental stresses such as salt stress. In the current study, the effects of priming of alfalfa seeds with sodium hydrosulfide (NaHS) (0.75 mM) as H2S-donor or SA (0.75 mM) on the improvement of germination indicators and the growth of seedlings under salt stress (0, 25, 50 and 100 mM) and also the decline of oxidative damages caused by salt stress (0 and 50 mM) were evaluated. The results showed that under unprimed conditions, salt stress had negative effects on different indicators of alfalfa seed germination and also on the growth of alfalfa seedlings. In addition, under unprimed conditions, the accumulation of malondialdehyde (MDA) and hydrogen peroxide (H2O2) significantly increased under salt stress. NaHS-priming and SA-priming showed positive effects on germination indicators and root length significantly increased in the seedlings obtained from NaHS- or SA-primed seeds. NaHS-priming and SA-priming decreased the accumulation of MDA and H2O2 under salt stress conditions showing the effect of priming treatments in decreasing oxidative stress. In addition, in response to salt stress, NaHS-priming and SA-priming significantly increased the levels of total sugars (especially 1 and 3 days after germination), when compared with their levels under unprimed conditions. Therefore, NaHS-priming and SA-priming treatments enhance plant responses in the first days after germination against salinity by reducing oxidative damages through activation of the antioxidant defense systems.

The surface species transformation of oxidized carrollite processing with NaHS and KBX was investigated. Flotation and contact angle tests indicate that the combination of NaHS and KBX takes a better flotation performance than adding NaHS or KBX alone. Thermodynamic analysis, X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) results confirm the stronger chemisorption of KBX occurs on the oxidized carrollite surface with NaHS, which is beneficial to remove the cobalt oxides, thus contributing to the superior floatability. Interestingly, less elemental sulfur was observed on the carrollite surface as the interaction of NaHS and KBX than adding NaHS alone. It suggests that elemental sulfur is not the main contributor to the restored floatability of oxidized carrollite through sulfidisation. This study provided a new perspective to correlate the surface species with xanthate adsorption and oxidized carrollite flotation through determining the various intermediate products.

Photodynamic therapy (PDT) is a non-surgical treatment that has been approved for its human medical use in many cancers. PDT involves the interaction of a photosensitizer (PS) with light. The amino acid 5- aminolevulinic acid (ALA) can be used as a pro-PS, leading to the synthesis of Protoporphyrin IX. Hydrogen sulfide (H 2 S) is an endogenously produced gas that belongs to the gasotransmitter family, which can diffuse through biological membranes and have relevant physiological effects such as cardiovascular functions, vasodilatation, inflammation, cell cycle and neuro-modulation. It was also proposed to have cytoprotective effects. We aimed to study the modulatory effects of H 2 S on ALAPDT in the mammary adenocarcinoma cell line LM2. Exposure of the cells to NaHS (donor of H 2 S) in concentrations up to 10 mM impaired the response to ALA-PDT in a dose-dependent manner. The addition of 3 doses of NaHS showed the highest effect. This decreased response to the photodynamic treatment was correlated to an increase in the GSH levels, catalase activity, a dose dependent reduction of PpIX and increased intracellular ALA, decreased levels of oxidized proteins and a decrease of PDT-induced ROS. NaHS also reduced the levels of singlet oxygen in an in vitro assay. H 2 S also protected other cells of different origins against PDT mediated by ALA and other PSs. These results suggest that H 2 S has a role in the modulation of the redox state of the cells, and thus impairs the response to ALA-PDT through multifactor pathways. These findings could contribute to developing new strategies to improve the effectiveness of PDT particularly mediated by ALA or other ROS-related treatments. [Display omitted] • H 2 S generated from NaHS make cells less sensitive to ALA-PDT. • H 2 S has multifactorial effects on ALA-PDT. • Supraphysiological but non-toxic concentrations of H 2 S have antioxidant activity. • Endogenous PpIX levels from ALA, decreases after NaHS treatment. [ABSTRACT FROM AUTHOR]

Background & objectives: Alzheimer’s disease (AD) patients suffer from anxiety and depression. Sodium hydrosulfide (NaHS) can remit the depressive-like and anxiety-like behaviors induced by diabetes mellitus. We aimed to investigate the effects of chronic administration of hydrogen sulfide on depressive and anxiety-like behaviors in the Streptozotocin (STZ) rat model of AD. Methods: Animals were divided into: Control, NaHS, and Alzheimer’s rats group include (STZ, STZ + Saline and STZ + NaHS groups) which were the Alzheimer’s rats and received Saline and NaHS (5.6 mg/kg per d) for 21 days. For induction of AD, STZ (3 mg/kg, 10 μl/injection site) was administered into the lateral ventricles. The behavioral consequences were assessed using plus maze, forced swim and sucrose preference tests. Results: Our results showed that intracerebroventricular (i.c.v.) injection of STZ decreased the percentage of open arm time and entries, indicating anxiety-like effects. It also increased the duration of immobility time and decreased the percentage of sucrose preference indicating depression-like effects. Sodium hydrosulfide administration in STZ-treated rats increased the percentage of open arm time and entries, indicating anxiolytic-like effects. It also decreased the duration of immobility time and increased the percentage of sucrose preference, indicating antidepressant-like effects. Conclusion: STZ administration can induce depression- and anxiety-like symptoms in rats, and Sodium hydrosulfide treatment, decreased the depression- and anxiety-like symptoms in STZ rat Model of AD, suggests that Sodium hydrosulfide can be useful in the treatment of affective disorders in AD patients.

Arslan Hussain Lodhi,1 Fiaz-ud-Din Ahmad,1 Kainat Furwa,1 Asadullah Madni2 1Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, PakistanCorrespondence: Fiaz-ud-Din AhmadDepartment of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Khawaja Fareed Campus, Railway Road, Bahawalpur, 63100, PakistanTel +92-320-8402376Email fazi2670@gmail.comPurpose: Persistent hyperglycemia lead towards depletion of hydrogen sulfide (H2S) resulting in generation of oxidative stress and diabetic nephropathy. The aim of the current study was to explore the antioxidant potential of H2S and captopril, a -SH containing compound in streptozotocin (STZ)-induced diabetic nephropathy.Methods: Fifty four Wistar-Kyoto (WKY) rats male (200– 250g) were divided into nine groups (n=6) with each group injected once with STZ (60mg/kg i.p) except normal control. After 3 weeks of induction of diabetes, groups were assigned as normal control, diabetic control, diabetic-captopril, diabetic-NaHS, diabetic-captopril-NaHS, diabetic-spironolactone, diabetic-metformin, diabetic-metformin-NaHS and diabetic-vitamin-c. All the animals were served with normal saline (N/S 4mL/kg p.o), captopril (50mg/kg/day p.o), sodium hydrosulfide (NaHS) (56μmol/kg i.p), spironolactone (50mg/kg/day s.c), metformin (500mg/kg/day p.o) and vitamin-c (50mg/kg p.o) on daily basis for next 4 weeks, respectively. Metabolic studies, H2S levels, renal hemodynamics and oxidative stress markers were analyzed at 0, 14 and 28 days followed by histopathological analysis of renal tissues.Results: The results showed decreased H2S levels, body weight, sodium to potassium ratio, glutathione (GSH), superoxide dismutase (SOD), total antioxidant assay (T-AOC) with malondialdehyde (MDA) and blood glucose levels significantly increased among diabetic rats. Treatment with captopril, NaHS, metformin, spironolactone and vitamin C showed significant improvement among renal hemodynamics and oxidative stress markers, respectively. But treatment groups like NaHS in combination with captopril and metformin showed more pronounced effects.Conclusion: The observations suggest that H2S mediated protective effects on STZ-induced diabetic nephropathy may be associated with reduced oxidative stress via augmenting the antioxidant effect.Keywords: captopril, diabetic nephropathy, oxidative stress, renal tissue, streptozotocin, sodium hydrosulfide

Hydrogen sulfide (H 2 S) prevents endothelial cells injury. However, the complicated mechanism of sodium hydrosulfide (NaHS, a donor that produces H 2 S) which inhibits the endothelial cells injury which correlated the activation of neutrophil in the type 1 diabetes mellitus (T1DM) rats has not been previously investigated. In the experiment, the T1DM animal model was established, the IL-1β, IL-8 were determined by western blotting and ELISA, the expressions of the Bax and Bcl-2 of endothelial cells and the CXCR2, CSE, phosphor-IκBα and NF-kB of neutrophils were measured by western blotting. Additionally, the concentration of serum dsDNA was tested by PicoGreen commercial Kits, changes in the H 2 S concentration of neutrophils were determined by Multiskan spectrum microphate spectrophotometer, the cellular ROS levels of neutrophils were detected by DCFH-DA staining and flow cytometry. The IL-1β, IL-8 concentration and expression increased, the endothelial cells injury which stimulated by high glucose and the concentration of dsDNA in serum increased, the expression of CXCR2, phosphor-IκBα and NF-kB increased while the expression of CSE and concentration of H 2 S decreased in neutrophils in the T1DM group compared to the control group. NaHS significantly inhibited the injury of endothelial cell, the production of ROS in neutrophils, reversed the expressions of CXCR2, CSE, phosphor-IκBα and NF-κB and decreased concentration of dsDNA in serum which were caused by T1DM. Our results demonstrated that the donor of H 2 S inhibits endothelial cells injury and neutrophils activation via the IL-8/CXCR2/ROS/NF-κB axis in T1DM rat. [Display omitted] • NaHS inhibits ECs injury and neutrophils activation in T1DM condition. • NaHS inhibits CXCR2 expression and NF-kB phosphorylation in T1DM neutrophils. • NaHS inhibits neutrophil activation involved in the IL-8/CXCR2/ROS/NF-κB axis. [ABSTRACT FROM AUTHOR]

Asthma is one of the most common respiratory diseases in the world. Nevertheless, it is reported that inflammation induced by asthma is not only restricted to the lung and may cause damaging effects on remote organs. Therefore, this study was designed to investigate the beneficial effects of long-term sodium hydrosulfide (NaHS) administration on lung inflammation and oxidative stress markers to protect the kidney during chronic asthma. BALB/c mice were divided into three groups (n = 5–7): control, asthma and NaHS. Except the control group, sensitization and challenge were performed with ovalbumin. The NaHS group intraperitoneally received 14 μmol/kg NaHS 30 min before each challenge. 24 h after the last challenge, samples of bronchoalveolar lavage fluid (BALF), plasma, lung and kidney tissues were collected. NaHS administration significantly decreased total white blood cell count, percentages of eosinophils, neutrophils and macrophages and increased percentage of lymphocytes. Administration of NaHS considerably decreased the levels of BALF interleukin-13, plasma tumor necrosis factor-alpha (TNF-α), lung malondialdehyde (MDA) and lung phosphorylated nuclear factor-kappa B (p-NF-κB) expression and scores of peribronchial inflammatory cell infiltration, goblet cell hyperplasia and subepithelial fibrosis and increased the activity of lung superoxide dismutase (SOD). The MDA levels and expressions of p-ERK1/2 and Bax were decreased and SOD activity and expressions of Bcl-2 and p-Akt were significantly increased in kidney tissues by NaHS administration. Administration of NaHS decreased renal oxidative stress indices and reduced apoptosis by the inhibition of TNF-α/ERK1/2/Bax. Therefore, H2S may have an essential role in renal protection during asthma. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) and hydrogen sulfide (H2S) are signalling molecules that regulate adventitious rooting in plants. However, little is known about the cross-talk between NO and H2S during adventitious rooting. Tomato (Solanum lycopersicum L.) explants were used to investigate the roles of and relationships between NO and H2S during rooting. Effects of the NO donor sodium nitroprusside (SNP) and the H2S donor sodium hydrosulfide (NaHS) on adventitious rooting were dose-dependent, and the greatest biological responses were observed under 25 µM SNP and 50 µM NaHS. The positive effect of NaHS was reversed by the NO scavenger 2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), indicating that the H2S-induced response was partially NO-dependent. Peroxidase (POD), polyphenol oxidase (PPO), and superoxide dismutase (SOD) activities significantly increased by SNP and NaHS treatment, and indoleacetic acid oxidase (IAAO) activity and the O2- and H2O2 content significantly decreased by SNP and NaHS treatment. SNP and NaHS treatment also increased the content of soluble sugar and protein and indole-3-acetic acid (IAA). cPTIO significantly mitigated the increases in POD, PPO and SOD activity and soluble sugar, protein and IAA content induced by NaHS. SNP and NaHS upregulated the expression of auxin-related genes (ARF4 and ARF16), cell cycle-related genes (CYCD3, CYCA3 and CDKA1), and antioxidant-related genes (TPX2, SOD and POD); whereas cPTIO significantly inhibited the increase in the expression of these genes induced by NaHS. Overall, these results show that NO may be involved in H2S-induced adventitious rooting by regulating the activity of rooting-related enzymes, the expression of related genes, and the content of various nutrients. [ABSTRACT FROM AUTHOR]

Background and aims: NaHS, a donor of hydrogen sulfide (H2S), which is emerging as a potential signaling molecule, may regulate various physiological processes in plants. However, how soybean (Glycine max L.) responds to NaHS and rhizobia (Sinorhizobium fredii) inoculation remains unclear. Methods: We explored the effects of NaHS and rhizobia on the growth rate, nodules, nitrogenase activities (NA), chlorophyll content, soluble protein content, photosynthesis (Pn), chlorophyll fluorescent parameters, endogenous H2S accumulation, l/d‐cysteine desulfhydrase (GmLCD and GmDCD) gene expression, nitrogen (N), phosphorus (P), potassium (K) contents, and nutrient resorption. Results: The results showed that rhizobia significantly increased the shoot, root, total dry weight, and growth rate, and NaHS promoted nodule numbers and NA in soybean. Moreover, chlorophyll content, soluble protein content, Pn, endogenous H2S accumulation, and GmLCD and GmDCD gene expression levels were promoted by NaHS and rhizobia. In addition, during all growth stages of soybean, the levels of N, P, and K and the N:P ratio in different tissues were affected by NaHS and rhizobia. Additionally, NaHS and rhizobia also significantly enhanced N resorption efficiency (NRE) and K resorption efficiency (KRE), but decreased P resorption efficiency (PRE). Conclusion: Therefore, NaHS and rhizobia regulated the growth rate, nutrient stoichiometry, and nutrient resorption efficiency of soybean. These findings provide information that will be useful for predicting how NaHS and rhizobia lead to variations in nutrient uptake and nutrient conservation strategies. [ABSTRACT FROM AUTHOR]

Background and aims: NaHS, a donor of hydrogen sulfide (H2S), which is emerging as a potential signaling molecule, may regulate various physiological processes in plants. However, how soybean (Glycine max L.) responds to NaHS and rhizobia (Sinorhizobium fredii) inoculation remains unclear. Methods: We explored the effects of NaHS and rhizobia on the growth rate, nodules, nitrogenase activities (NA), chlorophyll content, soluble protein content, photosynthesis (Pn), chlorophyll fluorescent parameters, endogenous H2S accumulation, l/d‐cysteine desulfhydrase (GmLCD and GmDCD) gene expression, nitrogen (N), phosphorus (P), potassium (K) contents, and nutrient resorption. Results: The results showed that rhizobia significantly increased the shoot, root, total dry weight, and growth rate, and NaHS promoted nodule numbers and NA in soybean. Moreover, chlorophyll content, soluble protein content, Pn, endogenous H2S accumulation, and GmLCD and GmDCD gene expression levels were promoted by NaHS and rhizobia. In addition, during all growth stages of soybean, the levels of N, P, and K and the N:P ratio in different tissues were affected by NaHS and rhizobia. Additionally, NaHS and rhizobia also significantly enhanced N resorption efficiency (NRE) and K resorption efficiency (KRE), but decreased P resorption efficiency (PRE). Conclusion: Therefore, NaHS and rhizobia regulated the growth rate, nutrient stoichiometry, and nutrient resorption efficiency of soybean. These findings provide information that will be useful for predicting how NaHS and rhizobia lead to variations in nutrient uptake and nutrient conservation strategies. [ABSTRACT FROM AUTHOR]

Gaseous molecules hydrogen sulfide (H2S) and salicylic acid (SA) enhance plant acclimation to environmental stresses such as salt stress. In the current study, the effects of priming of alfalfa seeds with sodium hydrosulfide (NaHS) (0.75 mM) as H2S-donor or SA (0.75 mM) on the improvement of germination indicators and the growth of seedlings under salt stress (0, 25, 50 and 100 mM) and also the decline of oxidative damages caused by salt stress (0 and 50 mM) were evaluated. The results showed that under unprimed conditions, salt stress had negative effects on different indicators of alfalfa seed germination and also on the growth of alfalfa seedlings. In addition, under unprimed conditions, the accumulation of malondialdehyde (MDA) and hydrogen peroxide (H2O2) significantly increased under salt stress. NaHS-priming and SA-priming showed positive effects on germination indicators and root length significantly increased in the seedlings obtained from NaHS- or SA-primed seeds. NaHS-priming and SA-priming decreased the accumulation of MDA and H2O2 under salt stress conditions showing the effect of priming treatments in decreasing oxidative stress. In addition, in response to salt stress, NaHS-priming and SA-priming significantly increased the levels of total sugars (especially 1 and 3 days after germination), when compared with their levels under unprimed conditions. Therefore, NaHS-priming and SA-priming treatments enhance plant responses in the first days after germination against salinity by reducing oxidative damages through activation of the antioxidant defense systems. [ABSTRACT FROM AUTHOR]

An efficient method for the catalytic thiomethylation of regioisomeric aminobenzamides with bis(N,N-dimethylamino)methane (formaldehyde) and H2S (Na2S · 9H2O, NaHS) leading to acyclic S-containing aminobenzamide derivatives or N,S-heterocycles has been developed. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is a neuromodulator in the central nervous system. The physiological function of H2S in the nucleus tractus solitarii (NTS) has rarely been reported. This research aimed to explore the role of H2S in regulating gastric functions. Wistar rats were randomly assigned to sodium hydrosulfide (NaHS; 4 and 8 nmol) groups, physiological saline (PS) group, capsazepine (10 pmol) + NaHS (4 nmol) group, L703606 (4 nmol) + NaHS (4 nmol) group, and pyrrolidine dithiocarbamate (4 nmol) + NaHS (4 nmol) group. The pH values of gastric acid were measured using a pH meter pre- and post-injection. It was found that the microinjetion of NaHS (4 and 8 nmol), an exogenous H2S donor, into the NTS (n = 6) remarkably decreased the pH values of gastric juice. The inductive effect of NaHS on gastric juice production could be suppressed by capsazepine (a transient receptor potential vanilloid 1 antagonist), L703606 (a NK1 receptor antagonist) and pyrrolidine dithiocarbamate (a nuclear fator-kB inhibitor). However, the same amount of PS did not induce any significant change in the pH value of gastric acid (P > 0.05). The findings of this study revealed that NaHS within the NTS remarkably promoted gastric acid secretion via the activation of TRPV1 channels and nuclear factor-γB-dependent mechanism in rats. [ABSTRACT FROM AUTHOR]

Quantum dots (QDs) have caused large challenges in clinical tests and biomedical applications due to their potential toxicity from nanosize effects and heavy metal components. In this study, the physiological responses of Phanerochaete chrysosporium (P. chrysosporium) to CdSe/ZnS QDs with either an inorganic sulfide NaHS or an organic sulfide cysteine as antidote have been investigated. Scanning electron microscope analysis showed that the hyphal structure and morphology of P. chrysosporium have obviously changed after exposure to 100 nM of COOH CdSe/ZnS 505, NH2 CdSe/ZnS 505, NH2 CdSe/ZnS 565, or NH2 CdSe/ZnS 625. Fourier transform infrared spectroscopy analysis indicated that the existence of hydroxyl, amino, and carboxyl groups on cell surface could possibly conduct the stabilization of QDs in an aqueous medium. However, after NaHS or cysteine treatment, the cell viability of P. chrysosporium exposed to CdSe/ZnS QDs increased as compared to control group, since NaHS and cysteine have assisted P. chrysosporium to alleviate oxidative damage by regulating lipid peroxidation and superoxide production. Meanwhile, NaHS and cysteine have also stimulated P. chrysosporium to produce more antioxidant enzymes (superoxide dismutase and catalase), which played significant roles in the defense system. In addition, NaHS and cysteine were used by P. chrysosporium as sulfide sources to promote the glutathione biosynthesis to relieve CdSe/ZnS QDs-induced oxidative stress. This work revealed that sulfide sources (NaHS and cysteine) exerted a strong positive effect in P. chrysosporium against the toxicity induced by CdSe/ZnS QDs. [ABSTRACT FROM AUTHOR]

The subject of study was the Safyanovskaya Med company's acidic underspoil water containing 0.17 g/liter of copper and 1.8 g/liter of zinc (pH 2.8–2.9). The goal was to study and develop a technology of cleaning water of impurities (copper, zinc, aluminum, iron, manganese), accompanied by extraction of copper and zinc in the form of commercial products. Copper extraction by cementation with metallic iron was studied. It was shown that this method could allow extracting 94–95% copper into a concentrate. The role of resolution processes of precipitated copper in cementation was established. To reduce the consumption of iron and to improve the quality of precipitated copper, it is proposed to carry out cementation in a washbox. The copper content in the concentrate was 27–28%, while the specific consumption of iron was 7.0–7.5 kg/kg of copper. During the studies of material composition of copper precipitate, the formation of cuprospinel, goethite, and bassanite phases and the precipitation of basic aluminum sulfates were detected. The extraction of zinc from the solution after copper removal was studied by precipitation with sodium sulfide. As a result, a concentrate was obtained with a zinc content of 49.6–50.9% with extraction of 99%. The process regularities for zinc concentrate dehydration were studied. By optimizing the crystallization conditions of the precipitate, a minimum final cake moisture content of 40–42% was reached. A process flow diagram for acidic underspoil water, including copper cementation and the precipitation of zinc sulfide, was developed. According to this diagram, the mother solution from zinc precipitation should be treated with lime until the pH reaches 10–10.5, followed by slurry settling. As a result, clean water of the following composition is obtained, mg/liter: 0.05 zinc, 0.01 copper, 0.02 aluminum, < 0.02 iron, 0.05 manganese. These values correspond to the quality of drinking water according to GOST R 51232-98. [ABSTRACT FROM AUTHOR]

While it is widely recognized that hydrogen sulfide (H 2 S) promotes plant stress tolerance, the precise processes through which H 2 S modulates this process remains unclear. The processes by which H 2 S promotes phosphorus deficiency (PD) and salinity stress (SS) tolerance, simulated individually or together, were examined in this study. The adverse impacts on plant biomass, total chlorophyll and chlorophyll fluorescence were more pronounced with joint occurrence of PD and SS than with individual application. Malondialdehyde (MDA), hydrogen peroxide (H 2 O 2), and electrolyte leakage (EL) levels in plant leaves were higher in plants exposed to joint stresses than in plants grown under an individual stress. When plants were exposed to a single stress as opposed to both stressors, sodium hydrosulfide (NaHS) treatment more efficiently decreased EL, MDA, and H 2 O 2 concentrations. Superoxide dismutase, peroxidase, glutathione reductase and ascorbate peroxidase activities were increased by SS alone or in conjunction with PD, whereas catalase activity decreased significantly. The favorable impact of NaHS on all the evaluated attributes was reversed by supplementation with 0.2 mM hypotaurine (HT), a H 2 S scavenger. Overall, the unfavorable effects caused to NaHS-supplied plants by a single stress were less severe compared with those caused by the combined administration of both stressors. • Salinity stress (SS) and phosphorus deficiency (PD) lowered plant growth and led to oxidative stress. • The detrimental effect of combined application of SS and PD was more marked on plant growth than their individual application. • NaHS, a donor of H 2 S, reduced oxidative stress and altered antioxidant enzymes' activities under SS or PD. • NaHS reduced Na+ and increased K+ contents under SS or SS + PD. • Hypotaurine, a H 2 S scavenger, reversed the positive effect of NaHS on plant tolerance to SS and PD. [ABSTRACT FROM AUTHOR]

• Consequence of Pb stress and NaHS growth regulator on morphological and anatomical features of mamodica charantia. • Antioxidants were checked. • Application of NaHS under the exposure to Pb stress significantly improved physica and biochemical structures of M. charantia. • Melatonin and other oxidants were alleviated in stress environment. Lead (Pb) is a toxic heavy metal that contaminates soil and water resources after its discharge from different industries. This research study was held to check the consequence of Pb stress and NaHS growth regulator on physicochemical features of Mamodica charantia. A pot experiment was conducted to determine the effect of NaHS (1 Mm and 1.5 Mm) for the screening of M. charantia exposed to severe Pb (500 ppm,1000 ppm and 2000 ppm) stress. Our results depicted that maximum growth of plants was recorded at 1.5 mM concentration, while inhibition was observed in the plants of M. charantia at highest concentration of lead chloride (2000 ppm). Significant positive change in agronomical structures of bitter melon like leaf, root, shoot, branches, root length and shoot length recorded at high concentration of NaHS growth regulator (1.5 mM). In case of lead stress study, plants show reduction in growth and development due to production of ROS species. ROS species reduced the concentration of divalent cations such Zn2+, Mn2+, Mg2+, Ca2+, and Fe2+ by restricting the flow of water. Leaves of M. charantia had lessen carotenoid and chlorophylls and enhanced activity of chlorophyllase in leaves. Biological content of antioxidants (CAT and POD), Protein and Proline were found maximum in NaHS treated plants while minimum in stressed plants. Nutrient content of root and shoot (K, Na and Ca) and morphological characteristics also behaved differently on different concentration of NaHS and Pb stress. Here, we concluded that the application of NaHS under the exposure to Pb stress significantly improved physiological and biochemical structures of M. charantia. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective(s): Prostaglandins have been shown to mediate the gastro-protective effect of sodium hydrosulfide (NaHS) but effect of NaHS on mRNA expression of prostaglandin E2 receptors (EP1, 3-4; EPs) has not been investigated. Therefore, this study designed to evaluate the effect of NaHS on mRNA expression of EPs receptors in response to mucosal acidification and distention-induced gastric acid secretion in rats. Materials and Methods: Fasted rats were randomly assigned into 4 groups (n=6/group). They were control, and NaHS-treated groups. To evaluate the effect of NaHS on mucosal mRNA expression of EPs receptors, the gastric mucosa exposed to stimulated gastric acid output and mucosal acidification. The pylorus sphincter catheterized for instillation of isotonic neutral saline or acidic solution. Ninety min after beginning the experiments, animals sacrificed and the gastric mucosa collected to determine the pH, mucus secretion and to quantify the mRNA expression of EPs receptors by quantitative real-time PCR. Results: present results showed that a) NaHS increased the mucus secretion, mRNA expression of EP3 and EP4 receptors in response to distention-induced expression; b) The mRNA expression of EP1 receptors increased while EP4 mRNA receptors decreased in response to mucosal acidification in NaHS-pretreated rats; and c) NaHS increased pH of gastric contents both in response to distention-induced gastric acid secretion and mucosal acidification. Conclusion: NaHS behaves in a different manner. It effectively only increased the pH of gastric contents to reinforce the gastric mucosa against a highly acidic solution but modulated both acid and mucus secretion when the rate of acid increase in the stomach was slower.

Temperature extremes represent an important limiting factor to plant growth and productivity. Low concentration of hydrogen sulfide (H2S) has been proven to function in physiological responses to various stresses. The present study evaluated the effect of foliar application of wheat seedlings with a H2S donor, sodium hydrosulfide (NaHS), on the response to acute heat stress. The results showed that pretreatment with NaHS could promote heat tolerance of wheat seedlings in a dose-dependent manner. Again, it was verified that H2S, rather than other sulfur-containing components or sodion derived from NaHS solution, should contribute to the positive role in promoting wheat seedlings against heat stress. To further study antioxidant mechanisms of NaHS-induced heat tolerance, superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6) and ascorbate peroxidase (APX, EC 1.11.1.11) activities, and H2S, hydrogen peroxide (H2O2), malonaldehyde (MDA), and soluble sugar contents in wheat seedlings were determined. The results showed that, under heat stress, the activities of SOD, CAT, and APX, H2S, H2O2, MDA, and soluble sugar contents in NaHS-pretreated seedlings and its control all increased. Meanwhile, NaHS-pretreated seedlings showed higher antioxidant enzymes activities and gene expression levels as well as the H2S and soluble sugar levels, and lower H2O2, MDA contents induced by heat stress. While little effect was detected in antioxidant enzymes activities and soluble substances contents in pretreated wheat seedlings compared with its control under normal culture conditions (data not shown). All of our results suggested that exogenous NaHS could alleviate oxidative damage and improve heat tolerance by regulating the antioxidant system in wheat seedlings under heat stress.

Hydrogen sulfide (H 2 S) has been identified as a novel gasotransmitter and a substantial antioxidant that can activate various cellular targets to regulate physiological and pathological processes in mammals. However, under physiological conditions, it remains unclear whether it is involved in regulating cardiomyocyte (CM) proliferation during postnatal development in mice. This study mainly aimed to evaluate the role of H 2 S in postnatal CM proliferation and its regulating molecular mechanisms. We found that sodium hydrosulfide (NaHS, the most widely used H 2 S donor, 50-200 μM) increased neonatal mouse primary CM proliferation in a dose-dependent manner in vitro. Consistently, exogenous administration of H 2 S also promoted CM proliferation and increased the total number of CMs at postnatal 7 and 14 days in vivo. Moreover, we observed that the protein expression of SIRT1 was significantly upregulated after NaHS treatment. Inhibition of SIRT1 with EX-527 or si-SIRT1 decreased CM proliferation, while enhancement of the activation of SIRT1 with SRT1720 promoted CM proliferation. Meanwhile, pharmacological and genetic blocking of SIRT1 repressed the effect of NaHS on CM proliferation. Taken together, these results reveal that H 2 S plays a promotional role in proliferation of CMs in vivo and in vitro and SIRT1 is required for H 2 S-mediated CM proliferation, which indicates that H 2 S may be a potential modulator for heart development in postnatal time window.

Studies suggest that hydrogen sulfide (H 2 S) plays a relevant and beneficial role in the pathophysiology of pulmonary allergic diseases, such as asthma. These diseases may be triggered by changes in airway epithelium caused by repeated exposure to environmental allergens. This study aimed to investigate whether H 2 S protects against bronchial epithelium apoptosis in allergic inflammation in mice. The effects of H 2 S on the production of Th2 cytokines and on the infiltration of pulmonary inflammatory cells were also studied. Female BALB/c mice previously sensitized with ovalbumin (OVA) were treated with H 2 S donor (sodium hydrosulfide [NaHS]) 30 min prior to OVA challenge. After euthanasia (48 h post challenge), the right lung was homogenized to study apoptosis protein expression and to analyze cytokine levels in lung tissue. The left lobe was fixed in formalin for morphological analysis of lung tissue and verification of apoptosis in situ by the TUNEL assay. Histological results showed that NaHS reduced the airway inflammatory infiltrate and prevented an increase in the IL-4, IL-5 and IL-25 levels caused by OVA challenge. Activation of caspase 3 and FasL in response to the allergen was also fully prevented by NaHS treatment. TUNEL staining showed that the challenge from OVA significantly increased the rate of apoptosis in the bronchiolar epithelium, and that this incremental apoptosis was abolished by NaHS treatment. In conclusion, our results showed that H 2 S donor has a protective effect against airway epithelium damage caused by an allergic reaction, and represents a potential agent in treating allergic lung disorders, such as asthma. • NaHS-treatment reduced lung IL-4, IL-5 and IL-25 increase induced by OVA-challenge. • Caspase 3/Fas-L increase in response to allergen were prevented by NaHS-treatment. • NaHS abolished apoptosis increase in bronchiolar epithelium induced by OVA-challenge. • H 2 S has a protective effect against lung damage caused by allergic reaction. [ABSTRACT FROM AUTHOR]

Erythrocytes change their micromechanical properties associated with membrane viscoelasticity when they perform the transport function. There is some evidence that this is due to the influence of signaling molecules, including such gasotransmitters as nitrogen oxide (NO) and hydrogen sulfide (H2S). The aim of this study was to investigate the changes in microrheology of human erythrocytes under the influence of donors and stimulants of endogenous formation of gasotransmitters. The erythrocyte deformability, assessed by the elongation index of erythrocytes (EIE), and aggregation parameters, the indices of aggregation of erythrocytes (IAE), of washed cells were recorded after their incubation with sodium nitroprusside (SNP); sodium hydrosulfide (NaHS), the donor of H2S; 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-l-one (ODQ), an inhibitor of soluble guanylate cyclase; L-arginine and N-nitroarginine methyl ester (L-NAME), a substrate and an inhibitor of NO synthase, respectively; and glibenclamide (GBC), the blocker of ATP-sensitive potassium channels. In addition, the resealed ghosts of erythrocytes were prepared, incubated with the above compounds, and the change in their deformability was evaluated. EIE increased by 8–11% (p < 0.01) and IAE decreased by 11–26% (p < 0.01) after the incubation of erythrocytes with SNP and NaHS, respectively. L-arginine and SNP exerted similar microrheological effects, which were eliminated by L-NAME or ODQ. GBC caused an increase in EIE by 8% (p < 0.05); the effects of GBC and NaHS were not additive. Incubation of the erythrocyte ghosts with SNP, L-arginine and NaHS was accompanied by a moderate but significant increase in membrane elasticity (p < 0.05). The obtained results indicate that the donors and stimulators of gasotransmitters NO and H2S moderately increase deformability of erythrocytes and markedly reduce their aggregability. The experiments on the erythrocyte ghosts suggest the existence of a direct effect of gasotransmitters on the viscoelastic properties of the membrane of these cells, which is independent of cGMP. [ABSTRACT FROM AUTHOR]

Abstract Hydrogen sulfide (H 2 S) is a gaseous molecule and is endogenously produced in the brain by cystathionine beta-synthase, 3-mercaptopyruvate-sulfurtransferase, cysteine aminotransferase and cystathionine γ-lyase. Physiologically, H 2 S acts as a neuromodulator and regulates synaptic activity of neurons and glia to promote the development of long-term potentiation. A decrease in H 2 S levels in the brain and plasma has been directly correlated with the degree of severity of Alzheimer disease in patients. A large number of studies have shown a decrease in the H 2 S levels in experimental models of cognitive dysfunction and exogenous administration of sodium hydrosulfide (NaHS), a H 2 S donor, has been shown to prevent the development of memory deficits. The beneficial effects of H 2 S in different models has been ascribed to decrease in neuroinflammation, up-regulation of antioxidant defense, decrease in endoplasmic reticulum (ER) stress, inhibition of phosphatidylinositol 3-kinase (PI3-K)/Akt signaling, inhibition of mitogen activated protein (MAP) kinases, decrease in glutamate and normalization of NMDA receptors, inhibition of matrix metalloproteinases (MMPs), up-regulation of silent information regulator 1 (Sirt 1) and preservation of mitochondrial function. The present review describes the role of H 2 S in different models of cognitive deficits and human subjects along with possible mechanisms. [ABSTRACT FROM AUTHOR]

Abstract Background Acute kidney injury is the most serious complication of crush syndrome. Hydrogen sulfide (H 2 S) is an endogenously produced gaseous signaling molecule. It is involved in homeostatic functions, such as blood pressure control, apoptosis, oxidative stress, and inflammation. In this study, effects of H 2 S on kidney injury were investigated in a rat model of crush syndrome. Methods Rats were divided into six groups (n = 8): Sham (steril saline ip), crush (sterile saline ip), crush + NaHS (sodium hydrosulfide, an H 2 S donor) (100 μmol/kg ip). All these groups were also separated as 3 and 24 h after decompression. Crush injury was induced by 6 h of direct compression to both hindlimbs of anesthetized rats with blocks weighing 3.6 kg each sides, followed by 3 or 24 h of decompression. Kidney injury molecule-1, neutrophil gelatinase–associated lipocalin, tumor-necrotizing factor-α, transforming growth factor-β, tissue total oxidant status, and total antioxidant status levels were measured in kidney homogenates 3 and 24 h after decompression. Serum creatine kinase, blood urea nitrogen, and creatinine levels were also measured. Apoptosis was assessed by TUNEL method. Bcl-2 was assessed by immunohistochemistry. Glomerular and tubular structures were also examined histopathologically. Results NaHS reduced kidney injury molecule-1, neutrophil gelatinase–associated lipocalin, tumor-necrotizing factor-α, transforming growth factor-β, total oxidant status levels, and increased total antioxidant status levels in kidney 3 and 24 h after decompression. Serum urea, creatinine, and creatine kinase levels also reduced with NaHS. NaHS decreased renal damage and apoptosis in crush-related acute kidney injury. Conclusions These results suggest that H 2 S could reduce crush-related acute kidney injury via anti-inflammatory, antioxidant, and antiapoptotic effects. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is an incurable disease caused by mutations in the X-linked DMD gene that encodes a structural muscle protein, dystrophin. This, in turn, leads to progressive degeneration of the skeletal muscles and the heart. Hydrogen sulfide (H 2 S), the pleiotropic agent with antioxidant, anti-inflammatory, and pro-angiogenic activities, could be considered a promising therapeutic factor for DMD. In this work, we studied the effect of daily intraperitoneal administration of the H 2 S donor, sodium hydrosulfide (NaHS, 100 μmol/kg/day for 5 weeks) on skeletal muscle (gastrocnemius, diaphragm and tibialis anterior) pathology in dystrophin-deficient mdx mice, characterized by decreased expression of H 2 S-generating enzymes. NaHS reduced the level of muscle damage markers in plasma (creatine kinase, lactate dehydrogenase and osteopontin). It lowered oxidative stress by affecting the GSH/GSSG ratio, up-regulating the level of cytoprotective heme oxygenase-1 (HO-1) and down-regulating the NF-κB pathway. In the gastrocnemius muscle, it also increased angiogenic vascular endothelial growth factor (Vegf) and its receptor (Kdr) expression, accompanied by the elevated number of α-SMA/CD31/lectin-positive blood vessels. The expression of fibrotic regulators, like Tgfβ , Col1a1 and Fn1 was decreased by NaHS in the tibialis anterior, while the level of autophagy markers (AMPKα signalling and Atg genes), was mostly affected in the gastrocnemius. Histological and molecular analysis showed no effect of H 2 S donor on regeneration and the muscle fiber type composition. Overall, the H 2 S donor modified the gene expression and protein level of molecules associated with the pathophysiology of DMD, contributing to the regulation of oxidative stress, inflammation, autophagy, and angiogenesis. [Display omitted] • The expression of H 2 S-generating enzymes is decreased in dystrophic mdx mice. • Markers of dystrophic conditions (CK, LDH, OPN) are improved after treatment with an H 2 S donor. • H 2 S donor exerts anti-inflammatory and anti-oxidative effects. • NaHS restores the expression of key angiogenic mediators in mdx animals and the number of blood vessels. • H 2 S has the potential to alleviate the hallmarks of Duchenne muscular dystrophy. [ABSTRACT FROM AUTHOR]

The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X 7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X 7 receptors.

Therapeutic strategies for neurological deficits and for promoting nerve regeneration after peripheral nerve injuries have received much focus in clinical research. Advances in basic research in recent years have increased our understanding of the anatomy of peripheral nerves and the importance of the microenvironment. Various new intervention methods have been developed, but with varying effectiveness. In the present study, we selected 911 papers on different repair methods for peripheral nerve injury from the Web of Science and indexed in the Science Citation Index from 2010 to 2014. We quantitatively examine new repair methods and strategies using bibliometrics, and we discuss the present state of knowledge and the problems and prospects of various repair methods, including nerve transfer, neural transplantation, tissue engineering and genetic engineering. Our findings should help in the study and development of repair methods for peripheral nerve injury.

With advances in biomedical methods, tissue-engineered materials have developed rapidly as an alternative to nerve autografts for the repair of peripheral nerve injuries. However, the materials selected for use in the repair of peripheral nerve injuries, in particular multiple injuries and large-gap defects, must be chosen carefully. Various methods and materials for protecting the healthy tissue and repairing peripheral nerve injuries have been described, and each method or material has advantages and disadvantages. Recently, a large amount of research has been focused on tissue-engineered materials for the repair of peripheral nerve injuries. Using the keywords "pe-ripheral nerve injury", "autotransplant", "nerve graft", and "biomaterial", we retrieved publications using tissue-engineered materials for the repair of peripheral nerve injuries appearing in the Web of Science from 2010 to 2014. The country with the most total publications was the USA. The institutions that were the most productive in this field include Hannover Medical School (Germany), Washington University (USA), and Nantong University (China). The total number of publications using tissue-engineered materials for the repair of peripheral nerve injuries grad-ually increased over time, as did the number of Chinese publications, suggesting that China has made many scientific contributions to this field of research.

Increasing evidence indicates that sialic acid plays an important role during nerve regeneration. Sialic acids can be modified in vitro as well as in vivo using metabolic oligosaccharide engineering of the N-acyl side chain. N-Propionylmannosamine (ManNProp) increases neurite outgrowth and accelerates the reestablishment of functional synapses in vitro. We investigated the influence of systemic ManNProp application using a specific in vivo mouse model. Using mice expressing axonal fluorescent proteins, we quantified the extension of regenerating axons, the number of regenerating axons, the number of arborising axons and the number of branches per axon 5 days after injury. Sciatic nerves from non-expressing mice were grafted into those expressing yellow fluorescent protein. We began a twice-daily intraperitoneal application of either peracetylated ManNProp (200 mg/kg) or saline solution 5 days before injury, and continued it until nerve harvest (5 days after transection). ManNProp significantly increased the mean distance of axonal regeneration (2.49 mm vs. 1.53 mm; P < 0.005) and the number of arborizing axons (21% vs. 16% P = 0.008) 5 days after sciatic nerve grafting. ManNProp did not affect the number of regenerating axons or the number of branches per arborizing axon. The biochemical glycoengineering of the N-acyl side chain of sialic acid might be a promising approach for improving peripheral nerve regeneration.

The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better regeneration was found with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel grafts than with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells grafts and the autologous nerve grafts.