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In recent years hydrogen sulfide (H2S) has demonstrated vasculoprotective effects against cell death, which suggests its promising therapeutic potential for numerous types of disease. Additionally, a protective effect of exogenous H2S in HG‑induced injuries in HUVECs was demonstrated, suggesting a potential protective effect for diabetic vascular complications. The present study aimed to investigate the mechanism accounting for the cytoprotective role of exogenous H2S against high glucose [HG (40 mM glucose)]‑induced injury and inflammation in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to HG for 24 h to establish an in vitro model of HG‑induced cytotoxicity. The cells were pretreated with sodium hydrosulfide (NaHS), a donor of H2S, or inhibitors of necroptosis and p38 MAPK prior to the exposure to HG. Cell viability, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), IL‑1β, IL‑6, IL‑8, TNF‑α, phosphorylated‑(p)38 and receptor‑interacting protein 3 (RIP3) expression levels were detected using the indicated methods, including Cell Counting Kit 8, fluorescence detection, western blotting, immunofluorescence assay and ELISAs. The results demonstrated that necroptosis and the p38 MAPK signaling pathway mediated HG‑induced injury and inflammation. Notably, NaHS was discovered to significantly ameliorate p38 MAPK/necroptosis‑mediated injury and inflammation in response to HG, as evidenced by an increase in cell viability, a decrease in ROS generation and loss of MMP, as well as the reduction in the secretion of proinflammatory cytokines. In addition, the upregulated expression of RIP3 induced by HG was repressed by treatment with SB203580, while the HG‑induced upregulation of p‑p38 expression levels were significantly downregulated following the treatment of Nec‑1 and RIP3‑siRNA. In conclusion, the findings of the present study indicated that NaHS may protect HUVECs against HG‑induced injury and inflammation by inhibiting necroptosis via the p38 MAPK signaling pathway, which may represent a promising drug for the therapy of diabetic vascular complications.

Diabetes mellitus (DM) facilitates atrial fibrosis and increases the risk of atrial fibrillation (AF). The underlying mechanism of DM in causing AF remains mostly unknown and potential therapeutic targets for DM‑induced AF are rarely reported. Hydrogen sulfide (H2S) has drawn considerable attention in recent years for its potential as a cardiovascular protector. Thus, the aim of the present study was to investigate the effect of H2S on DM‑induced AF and the mechanism of action. Sprague‑Dawley rats were divided into four groups, including the control group, the DM group, the H2S group and the DM+H2S group. The DM group and the DM+H2S group were administered streptozotocin to induce DM, whereas the other two groups were given citrate buffer as a control. The H2S group and the DM+H2S group were administered with an intraperitoneal injection of sodium hydrosulfide (precursor of H2S). AF inducibility, AF duration, atrial fibrosis and vital protein expression of oxidative stress were compared among the four groups. The DM group showed significantly higher AF incidence rates and duration (P

Hydrogen sulfide (H2S) is a gas signaling molecule that has multiple influences on physiological and pathological processes in the mammalian body, including vasodilation, neurotransmission, inflammation, hypoxia sensing and bone remodeling. Our previous studies suggested that H2S might be involved in the periodontal tissue remodeling during the orthodontic tooth movement (OTM) via increasing periodontal ligament cell differentiation, tissue mineralization, bone formation and collagen synthesis. The aim of the present study was to investigate the effects of H2S on alveolar bone remodeling that is associated with tooth movement. Experiments were performed in an OTM mouse model. Sodium hydrosulfide (NaHS), which is a donor of H2S and DL-propargylglycine (PAG) and a cystathionine-γ-lyase (CSE) inhibitor, which could also decrease H2S expression, were administered intraperitoneally and respectively. A total of 60 male C57BL6/J mice were divided into 4 groups; Control, NaHS, PAG and combination (PAG+NaHS). The rate of OTM and the bone mineral density (BMD) of alveolar bone were scanned and measured by micro-computed tomography (micro-CT). The number of osteoclasts and expression of the tumor necrosis factor ligand superfamily member-11 (RANKL), alkaline phosphatase (ALP), osteocalcin (OCN) and osteoprotegerin (OPG) in alveolar bone were accessed to evaluate the osteoclastic activity and osteogenesis with histochemistry of tartrate-resistant acid phosphatase staining, immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. In the alveolar bone, NaHS increased the OTM and decreased the BMD, respectively. PAG significantly decrease OTM and increased the BMD. NaHS combined with PAG rescued the PAG-induced changes in the OTM and the BMD. Additionally, the number of osteoclasts, the expression of RANKL, ALP, OCN and the ratio of RANKL/OPG were significantly up-regulated in the NaHS group. In contrast, PAG down-regulated the number of osteoclasts, the expression of RANKL, ALP, OCN and the ratio of RANKL/OPG. These findings suggested that H2S might facilitate the OTM by enhancing alveolar bone remodeling as a result of an increased osteoclastic activity and osteogenesis.

The aim of the present study was to investigate the effects of hydrogen sulfide (H2S) on the activity and expression of inducible nitric oxide synthase (iNOS) in the myocardial tissue of type 1 diabetic rats. Rats were divided randomly into four groups: Normal control (NC), diabetes mellitus (DM), DM+DL‑Proparglygylcine (DM+PAG) and DM+sodium hydrosulfide (DM+NaHS) groups. Type 1 diabetes was induced in the respective groups by a single intraperitoneal (i.p.) injection of streptozotocin. Rats in the DM+PAG and DM+NaHS groups were injected with PAG and NaHS (i.p.) once a day, respectively. The level of fasting blood glucose (FBG), the heart‑weight to body‑weight (HW/BW) ratio and the ventricular hemodynamic parameters were measured. The activities of serum total NOS (tNOS), iNOS, lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase MB isozyme (CK‑MB), and the content of nitric oxide (NO) were detected. The contents of myocardial malondialdehyde (MDA) and NO, and the activities of superoxide dismutase (SOD), tNOS and iNOS were determined. The myocardial tissue was examined for histological and ultrastructural alterations. The expression level of iNOS at the transcriptional and translational levels in the myocardial tissue was estimated. The level of FBG was increased in the DM group compared with the NC group, verifying the diabetic condition of the rats. The function of the left ventricle, the myocardial histological alterations and ultrastructures were damaged in the DM group. The DM group additionally demonstrated an increase in the serum NO content and tNOS, iNOS, LDH, CK and CK‑MB activities. The myocardial MDA, NO content and tNOS levels were additionally increased in this group. The iNOS activity was increased significantly whereas the myocardial SOD activity was decreased. The increase in the iNOS activity was supported by an enhanced expression level of myocardial iNOS mRNA and protein in the DM group. In the DM+PAG group, in the absence of H2S, the dysfunction of the left ventricle and the oxidative stress injury were increased compared with the DM group. The activity and the expression of tNOS and iNOS were increased significantly. However, the rats in the DM+PAG group demonstrated the opposite effects. In conclusion, H2S exhibits a protective effect on the myocardium in type 1 diabetic rats, which may be associated with the suppression of iNOS activity and expression, a decrease in the NO content and the inhibition of oxidative stress injury.

The inhibitory effects of hydrogen sulfide (H2S) on angiotensin II (AngII)-stimulated human umbilical vein endothelial cell (HUVEC) dysfunction remain to be elucidated. Endoplasmic reticulum (ER) stress has been detected in endothelial dysfunction (ED). The present study aimed to determine whether H2S may exert an inhibitory effect on AngII‑induced ER stress. Using HUVECs as a model system, the present study used western blotting to detect protein expression, intracellular reactive oxygen species (ROS) levels were determined by oxidative conversion of cell permeable DCFH‑DA to fluorescent dichlorofluorescein, CCK‑8 assay was used to investigate the cell viability, methylene blue was used to investigate the CSE activity, TUNEL was used to investigate the cells apoptosis. The present study demonstrated that AngII not only upregulated the expression levels of inducible nitric oxide synthase (iNOS), stimulated ROS production and increased cell apoptosis, but also downregulated the expression levels of phosphorylated‑endothelial nitric oxide synthase, decreased the expression and activity of cystathionine‑c‑lyase (CSE) and decreased cell viability. Furthermore, hydrogen peroxide (H2O2; an exogenous ROS) downregulated the expression and activity of CSE, and had similar effects as AngII, whereas the inhibitory effects of AngII were completely suppressed by N-acetyl-L-cysteine (a ROS scavenger). In addition, AngII induced the expression of glucose‑regulated protein 78 (GRPP78) and C/EBP homologous protein (CHOP), which are markers of ER stress. Conversely, the stimulatory effects of AngII were completely inhibited by sodium hydrosulfide (NaHS; a H2S donor). Treatment with NaHS attenuated ROS production, inhibited CHOP and GRP78 expression, and decreased cell apoptosis. The present study indicated that AngII induced ED via the activation of ER stress in HUVECs. In addition, the effects of AngII on ER stress could be suppressed by H2S.

Hydrogen sulfide (H2S) has been demonstrated to have various effects on mitochondrial function. The aim of the present study was to investigate the effects of H2S on mitochondrial fission and the potential underlying mechanisms of these effects. Transmission electron microscopy analysis demonstrated that sodium hydrosulfide (NaHS, a donor of H2S) inhibited mitochondrial fission in a dose‑ and time‑dependent manner. Treating neuro‑2a (N2a) mouse neuroblastoma cells with 400 µM NaHS for 16 h significantly increased the % of elongated mitochondria and reduced the number of mitochondria per cell compared with untreated cells. In addition, the viability and ATP generation of N2a cells that were treated with various concentrations of NaHS was examined. The results demonstrated that treatment with 400 and 600 µM NaHS increased cell viability and ATP generation compared with untreated cells. To further understand the effects of H2S on mitochondrial morphology, the protein and mRNA expression levels of dynamin 1 like (Dnm1l, also known as Drp1) were examined, and the results demonstrated that NaHS dose‑dependently reduced Drp1 mRNA and protein levels, consistent with the mitochondrial morphology changes. To determine whether H2S affects mitochondrial morphology through Drp1 expression, Drp1 was overexpressed in N2a cells using a lentivirus encoding the Drp1 cDNA. It was observed that Drp1 overexpression reversed the effects of NaHS. Furthermore, NaHS promoted the phosphorylation of extracellular signal‑regulated kinase (ERK) 1/2, and the effects of NaHS on Drp1 expression were abolished by an ERK1/2 inhibitor (PD98059). The results of the present study indicate that the H2S‑induced decrease in Drp1 mRNA and protein levels and mitochondrial fission may involve the ERK1/2 signaling pathway. The present study suggests that H2S may be used in the future as a potential therapeutic for diseases that may be mediated by abnormal mitochondria fragmentation, such as Alzheimer's disease.

Aberrant lipid metabolism contributes to the development of type 2 diabetes mellitus. The mechanisms by which hydrogen sulfide (H2S), an endogenous gasotransmitter, regulates lipid metabolism remain unclear. The aim of the present study was to investigate if the protective effects of H2S during high glucose (HG)-induced lipid accumulation in 3T3-L1 adipocytes may be mediated by AMP-activated protein kinase (AMPK). Triglyceride (TG) content and the production of H2S were determined using adipogenesis colorimetric assay kits and H2S synthesis methods. The levels of monocyte chemoattractant protein-1 and adiponectin were evaluated by ELISA. Total AMPK and phosphorylated AMPK levels were assessed by western blot analysis. HG increased the cellular level of TG and decreased H2S production in 3T3-L1 adipocytes. The H2S donor, sodium hydrosulfide (NaHS) protected against the HG-induced accumulation of TG in 3T3-L1 adipocytes. Furthermore, NaHS suppressed HG-induced TG accumulation by activating AMPK. Collectively, the findings of the present study suggested that HG induced lipid accumulation in 3T3-L1 adipocytes, and AMPK activation may underlie the lipid-lowering effects of H2S.

The effects of hydrogen sulfide (H2S) and the nuclear factor κB (NF-κB) signaling pathway in angiotensin II (AngII)-induced endothelin-1 (ET-1) expression and subsequent cytotoxicity remain unclear. The present study aimed to investigate the hypothesis that H2S protects human umbilical vein endothelial cells (HUVECs) against AngII‑stimulated ET‑1 generation and subsequent cytotoxicity‑induced endoplasmic reticulum stress via the NF‑κB signaling pathway. The results of the present study demonstrated that AngII significantly upregulated the expression levels of ET‑1, glucose‑regulated protein 78, CCAAT‑enhancer‑binding protein homologous protein, phosphorylated (p)‑p65 and inducible nitric oxide synthase; stimulated nitric oxide production; suppressed the expression and activity of cystathionine-γ-lyase (CSE), a H2S synthetase; and decreased cell viability. Conversely, BQ788 (an ET‑1 receptor antagonist) exhibited an inhibitory effect on the AngII‑mediated suppression of CSE expression and activity in HUVECs. The effects of AngII were abrogated by sodium hydrosulfide (NaHS, an H2S donor), BQ788 or pyrrolidinedithiocarbamic acid (PDTC, an inhibitor of NF‑κB). Furthermore, pretreatment with NaHS or PDTC attenuated AngII‑induced apoptosis and cleaved caspase-12 generation. The pretreatment of HUVECs with BQ788 prior to AngII exposure mimicked the inhibitory effect of NaHS on the expression of p‑p65 induced by AngII. In conclusion, the present study provides evidence that exogenous H-2S attenuates AngII‑induced inflammation and cytotoxicity via inhibition of the ET‑1/NF‑κB signaling pathway in HUVECs.

Korean bamboo salt (BS) is known to have therapeutic effects in the treatment of diseases, including viral disease, dental plaque, diabetes, circulatory organ disorders, cancer and inflammatory disorders. However, the effect of BS on immune functions remains to be elucidated. The present study was designed to determine the immune‑enhancing effect of BS and its component, hydrogen sulfide, using RAW264.7 macrophages and a forced swimming test (FST) animal model. BS and sodium hydrosulfide (NaSH), a hydrogen sulfide donor, significantly increased the levels of tumor necrosis factor (TNF)‑α through the activation of nuclear factor‑κB in the RAW 264.7 cells. In an in vivo experiment, BS and NaSH were administered orally once a day for 28 days. After the 28 days, the immobility times in the FST were significantly decreased in the BS and NaSH‑fed groups, compared with the control group. In addition, BS and NaSH induced significant increases in the levels of interferon‑γ, interleukin‑2 and TNF‑α, compared with the control group. Taken together, these results indicated that BS and NaSH may improve immune function.

Doxorubicin (DOX) is a widely used chemotherapeutic agent, which can give rise to severe cardiotoxicity, limiting its clinical use. Preliminary evidence suggests that hydrogen sulfide (H2S) may exert protective effects on DOX‑induced cardiotoxicity. Therefore, the aim of the present study was to investigate whether peroxiredoxin III is involved in the cardioprotection of H2S against DOX‑induced cardiotoxicity. The results demonstrated that DOX not only markedly induced injuries, including cytotoxicity and apoptosis, it also increased the expression levels of peroxiredoxin III. Notably, pretreatment with sodium hydrosulfide significantly attenuated the DOX‑induced decrease in cell viability and increase in apoptosis, and also reversed the increased expression levels of peroxiredoxin III in H9c2 cardiomyocytes. In addition, pretreatment of the H9c2 cells with N‑acetyl‑L‑cysteine, a scavenger of reactive oxygen species, prior to exposure to DOX markedly decreased the expression levels of peroxiredoxin III. In conclusion, the results of the present study suggested that exogenous H2S attenuates DOX‑induced cardiotoxicity by inhibiting the expression of peroxiredoxin III in H9c2 cells. In the present study, the apoptosis of H9c2 cardiomyocytes was assessed using an methyl thiazolyl tetrazolium assay and Hoechst staining. The levels of Prx III and cystathionine-γ-lyase were examined by western blotting.

The present study aimed to investigate the effects of endogenous hydrogen sulfide (H2S) on the expression levels of angiotensin II type 1 receptor (AGTR1) in a rat model of carbon tetrachloride (CCl4)-induced hepatic fibrosis. A total of 56 Wistar rats were randomly divided into four groups: Normal control group, model group, sodium hydrosulfide (NaHS) group, and DL-propargylglycine (PAG) group. Hepatic fibrosis was induced by CCl4. The rats in the PAG group were intraperitoneally injected with PAG, an inhibitor of cystathionine-γ-lyase (CSE). The rats in the NaHS group were intraperitoneally injected with NaHS. An equal volume of saline solution was intraperitoneally injected into both the control and model groups. All rats were sacrificed at week three or four following treatment. The serum levels of hyaluronidase (HA), laminin protein (LN), procollagen III (PcIII), and collagen IV (cIV) were detected using ELISA. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and albumin (ALB) were detected using an automatic biochemical analyzer. The liver mRNA expression levels of CSE were detected by reverse transcription-quantitative polymerase chain reaction. The liver expression levels of AGTR1 and the plasma expression levels of H2S were detected using western blot analyses. The results indicated that the severity of hepatic fibrosis, the serum expression levels of HA, LN, PcIII, cIV, ALT, and AST, the liver expression levels of CSE and AGTR1, and the plasma expression levels of H2S were significantly higher in the PAG group, as compared with the model group (P

Sodium hydrosulfide (NaHS) is an exogenous hydrogen sulfide (H2S)-releasing molecule and has antitumor potential against a wide variety of human cancer types. The effect of exogenous H2S on the invasion of breast cancer and the possible underlying mechanisms remain unknown. The present study aimed to investigate the in vitro effects of H2S on transforming growth factor-β1 (TGF-β1)-induced human breast cancer cells and the associated mechanisms. MCF-7 cells were incubated with TGF-β1 to induce epithelial-mesenchymal transition (EMT) and an MTT assay was performed to detect cell viability. Flow cytometry, using propidium iodide (PI) staining, was used to determine the stages of the cell cycle. Apoptosis was detected with Annexin V-fluorescein isothiocyanate and PI double staining. Western blotting was performed to detect the protein expression of cystathionine γ-lyase (CSE, an endogenous H2S producer), phospho-p38 (a signaling protein associated with apoptosis), and SNAI1 (Snail, associated with the induction of EMT). A Boyden chamber invasion assay was performed to detect tumor invasion. The results demonstrated that when NaHS was administered to TGF-β1-treated MCF-7 cells, the cells exhibited decreased proliferation, G0/G1 phase cell cycle arrest and increased apoptosis. NaHS treatment following TGF-β1 administration also resulted in decreased cell invasion and decreased EMT, which was indicated by decreased Snail protein expression. In addition, incubation with NaHS increased endogenous CSE protein expression and decreased p38 mitogen-activated protein kinase phosphorylation in MCF-7 cells stimulated by TGF-β1. Furthermore, the inhibition of endogenous CSE by DL-propargylglycine increased EMT in the MCF-7 cells treated with NaHS and TGF-β1. In conclusion, the present study provides insights into a novel anticancer effect of H2S on breast cancer cells through activation of the CSE/H2S pathway and decreased expression of phospho-p38.

It was previously confirmed that hydrogen sulfide (H2S) has a neuroprotective effect, preventing homocysteine‑induced neurotoxicity. However, the exact molecular mechanisms underlying this protective effect remain to be fully elucidated. Endoplasmic reticulum (ER) stress contributes to homocysteine‑induced neurotoxicity. Silent mating type information regulator 2 homolog 1 (SIRT‑1) can attenuate ER stress, exerting its neuroprotective effect. Therefore, the present study aimed to investigate whether H2S protects PC12 cells against homocysteine‑induced ER stress and whether SIRT‑1 mediates this protective effect of H2S. Western blotting was used to detect the expression of SIRT‑1, glucose‑regulated protein 78 (GRP78), and cleaved caspase‑12 in PC12 cells. It was observed that sodium hydrosulfide (NaHS), an exogenous H2S donor, significantly attenuated the homocysteine‑induced ER stress responses, including increases in the protein expression levels of GRP78 and cleaved caspase‑12. Simultaneously, NaHS upregulated the expression of SIRT‑1 and reversed the homocysteine‑induced downregulation of SIRT‑1 in PC12 cells. Sirtinol, a specific inhibitor of SIRT‑1, eliminated the protective effects of H2S in homocysteine‑induced ER stress. These data indicated that H2S prevented homocysteine‑induced ER stress via enhancing the expression of SIRT‑1. These findings offer novel insight into the protective mechanisms of H2S against homocysteine‑induced neurotoxicity.

Angiotensin II (Ang II) has been reported as key in inducing endothelial cell injury, and endothelial cells may produce nitric oxide (NO) to protect themselves. However, the underlying mechanism remains elusive. Human umbilical vein endothelial cells (HUVECs) were divided into five treatment groups as follows: Normal control, Ang II, Ang II + sodium hydrosulfide [NaHS; hydrogen sulfide (H2S) donor], Ang II + Akt inhibitors + NaHS, and Ang II + endothelial nitric oxide synthases (eNOS) inhibitors + NaHS. Subsequently, cell viability, apoptosis, migration, proliferation and adhesion ability were determined. In addition, tubular structure formation was observed, and the NO and phosphorylation levels of Akt and eNOS were evaluated. Compared with the normal control group, Ang II treatment reduced the viability of HUVECs and increased the level of cell apoptosis (P

Hydrogen sulfide (H2S) has been recently found to be an endogenous signaling gasotransmitter. Cardiac hypertrophy often develops in the course of heart failure. It is unknown whether or not endogenous H2S protects cardiac hypertrophy. This study was conducted to examine the effects of H2S on cardiac hypertrophy and fibrosis induced by abdominal aortic coarctation and to explore its mechanisms. Male Sprague-Dawley rats were randomly divided into five groups: normal, sham, abdominal aortic coarctation (AAC), AAC treated with enalapril and AAC treated with H2S. One week after surgery, enalapril and sodium hydrosulfide (NaHS)-treated rats were fed for 28 consecutive days and sacrificed. After that, the left ventricle mass index (LVMI), cardiomyocyte size and areas, collagen volume fraction (CVF) of the rats were measured. In the AAC rats, the LVMI, the cardiomyocyte size and areas, and the CVF were all markedly increased while in the H2S groups they were significantly reduced. H2S decreased the levels of Ang-II in the heart, but not in plasma. In addition, H2S also improved the expression of connexin 43 (Cx43). Our results suggest that H2S can significantly suppress cardiac hypertrophy and fibrosis induced by overloaded pressure, possibly by inhibiting the activity of intracardiac Ang-II and by modifying expression of Cx43.

Myocardial fibrosis is the predominant pathological characteristic of diabetic myocardial damage. Previous studies have indicated that hydrogen sulfide (H2S) has beneficial effects in the treatment of various cardiovascular diseases. However, there is little research investigating the effect of H2S on myocardial fibrosis in diabetes. The present study aimed to investigate the effects of H2S on the progression of myocardial fibrosis induced by diabetes. Diabetes was induced in rats by intraperitoneal injection of streptozotocin. Sodium hydrosulfide (NaHS) was used as an exogenous donor of H2S. After 8 weeks, expression levels of cystathionine-γ-lyase were determined by western blot analysis and morphological changes in the myocardium were assessed by hematoxylin and eosin staining and Masson staining. The hydroxyproline content and fibrosis markers were determined by a basic hydrolysis method and western blot analysis, respectively. Autophagosomes were observed under transmission electron microscopy. Expression levels of autophagy-associated proteins and their upstream signaling molecules were also evaluated by western blotting. The results of the current study indicated that diabetes induced marked myocardial fibrosis, enhanced myocardial autophagy and suppressed the phosphatidylinositol-4,5-bisphosphate 3-kinase/RAC-α serine/threonine-protein kinase (PI3K/AKT1) signaling pathway. By contrast, following treatment with NaHS, myocardial fibrosis was ameliorated, myocardial autophagy was decreased and the PI3K/AKT1 pathway suppression was reversed. The results of the present study demonstrated that the protective effect of H2S against diabetes-induced myocardial fibrosis may be associated with the attenuation of autophagy via the upregulation of the PI3K/AKT1 signaling pathway.

Doxorubicin (DOX) is a potent and currently available antitumor therapeutic agent; however, its clinical application is limited by the occurrence of cardiotoxicity. Preliminary evidence indicates that hydrogen sulfide (H2S) may exert protective effects against DOX cardiotoxicity. Therefore, the aim of the present study was to investigate whether calreticulin (CRT) is involved in the cardioprotection of H2S against DOX‑induced cardiotoxicity. DOX was observed to markedly induce injuries, including cytotoxicity and apoptosis, and also enhance the expression level of CRT. Notably, pretreatment of H9c2 cells with sodium hydrosulfide (a donor of H2S) significantly attenuated the decreased cell viability, the increased apoptosis rate and the increased expression level of CRT in H9c2 cells. In addition, pretreatment of H9c2 cells with N‑acetyl‑L‑cysteine, a scavenger of reactive oxygen species (ROS) prior to exposure to DOX, markedly decreased the expression of CRT. These results indicate that exogenous H2S attenuates DOX‑induced cardiotoxicity by inhibiting CRT expression in H9c2 cardiac cells.

Hydrogen sulfide (H2S) is a naturally occurring gaseous transmitter, which is important in normal physiology and disease. In the present study, the involvement of H2S in the regulation of the immune response induced by burn injury was investigated in mice. Adult male C57BL/6 mice were subjected to burn injuries and treated with vehicle (0.9% sodium chloride, NaCl; 100 ml/kg body weight; subcutaneously, s.c.) or the H2S donor (sodium hydrosulfide, NaHS; 2 mg/kg body weight; s.c.). Compared with the controls, mice which received burn injuries exhibited a significant decrease in plasma H2S levels. Moreover, the levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑8 significantly increased, while IL‑10 levels were decreased, compared with that of the controls in the plasma of mice subjected to burn injuries. Myeloperoxidase (MPO) activity in the liver tissue of injured mice was also markedly higher compared with that of the control group. However, the administration of NaHS significantly decreased the levels of TNF‑α, IL‑6 and IL‑8 but increased the levels of IL‑10 in the plasma of mice subjected to burn injuries. In addition, the MPO activity was decreased by NaHS. These results suggested that H2S regulates the inflammatory response induced by burn injury by modulating the levels of TNF‑α, IL‑6, IL‑8 and IL‑10. Thus, it was proposed that the administration of the H2S donor, NaHS, may be a useful therapy against the exaggerated immune response that is associated with burn injury.

Peripheral artery disease (PAD) may lead to a poor quality of life. Although percutaneous transluminal angioplasty (PTA) is widely used for the treatment of PAD, restenosis remains a major drawback. Hydrogen sulfide (H2S) plays potential roles in many physiological processes, such as vasodilatation and inhibition of smooth muscle cell proliferation. However, little is known regarding its role in arterial restenosis. In this study, we induced atherosclerotic-like lesions in rabbits, and we treated the rabbits with balloon angioplasty (BA) in a similar manner as PTA performed in the clinic. The rabbits were treated with sodium hydrosulfide (NaHS, a donor of H2S) or DL-propargylglycine (PPG, an inhibitor of H2S synthase). Treatment with NaHS significantly inhibited arterial restenosis following BA by reducing the intimal area and the intima/media ratio, while PPG treatment had a tendency to result in more severe restenosis. NaHS treatment significantly reduced smooth muscle cell (SMC) proliferation and elevated SMC apoptosis in the neointima. In contrast, PPG induced a significant increase in SMC proliferation. In conclusion, H2S attenuates the progression of neointimal hyperplasia and inhibits restenosis after BA. This discovery may lead to potential novel therapies, which can improve the prognosis of PAD patients.