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Hydrogen sulfide (H2S), an endogenous gasotransmitter, plays an important role in apoptosis. Exudative diathesis (ED) disease is associated with dietary selenium (Se) deficiency in broilers. The liver is one of the target organs of Se deficiency; however, little is known about the effect of H2S on apoptosis via mitochondrial pathways in the livers of broilers with ED disease. In the present study, we aimed to investigate the correlation between endogenous H2S and mitochondrial-mediated apoptosis in the livers of broilers with ED disease, as induced by Se deficiency. One hundred twenty healthy, 1-day-old broilers were randomly assigned to one of two groups (60 each) based on diet: Basal diet (control group, 0.2 mg/kg Se) or a low-Se diet (−Se group, 0.033 mg/kg Se). At day 20, 15 broilers of a similar weight were sacrificed from the control group, while the same number of broilers were euthanatized from the −Se group when displaying typical symptoms of ED between days 18 and 25. The livers were collected, and apoptosis was measured using a TUNEL assay. Additionally, H2S concentration, the expression of H2S synthases of cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST), as well as mitochondrial apoptosis-related genes of Bcl-2, Bax, Bak, Cyt-C, Caspase-9, Caspase-3, and p53, were examined in livers. The results indicated that Se deficiency could induce apoptosis in the livers of broilers. Swelling, fractures, and vacuolization were visible in the mitochondrial cristae in the livers of the −Se group. The expression of H2S synthase-related genes and H2S concentration was significantly enhanced (P < 0.05) in the livers of the −Se group compared to controls. Moreover, a low-Se diet downregulated (P < 0.05) the level of Bcl-2 and upregulated (P < 0.05) the levels of Bax, Bak, Cyt-C, Caspase-9, Caspase-3, and p53. These results suggest that an H2S increase in the livers of ED broilers, which was induced by Se deficiency, is related to apoptosis mediated by mitochondrial pathways.

Objectives: To investigate the antioxidative properties of sulfurous drinking water after a standard hydropinic treatment (500 ml day-1 for 2 weeks). Subjects/Methods: Forty apparently healthy adults, 18 men and 22 women, age 41-55 years old. The antioxidant profile and the oxidative condition were evaluated in healthy subjects supplemented for 2 weeks with (study group) or without (controls) sulfurous mineral water both before (T0) and after (T1) treatment. Results: At T1, a significant decrease (P<0.05) in both lipid and protein oxidation products, namely malondialdehyde, carbonyls and AOPP, was found in plasma samples from subjects drinking sulfurous water with respect to controls. Concomitantly, a significant increment (P<0.05) of the total antioxidant capacity of plasma as well as of total plasmatic thiol levels was evidenced. Tocopherols, carotenoids and retinol remained almost unchanged before and after treatment in both groups. Conclusions: The improved body redox status in healthy volunteers undergoing a cycle of hydropinic therapy suggests major benefits from sulfurous water consumption in reducing biomolecule oxidation, possibly furnishing valid protection against oxidative damage commonly associated with aging and age-related degenerative diseases.

Manganese-based nanomaterials have piqued great interest in cancer nanotheranostics, owing to their excellent physicochemical properties. Here we report a facile wet-chemical synthesis of size-controllable, biodegradable, and metastable γ-phase manganese sulfide nanotheranostics, which is employed for tumor pH-responsive traceable gas therapy primed chemodynamic therapy (CDT), using bovine serum albumin (BSA) as a biological template (The final product was denoted as MnS@BSA). The as-prepared MnS@BSA can be degraded in response to the mildly acidic tumor microenvironment, releasing hydrogen sulfide (H S) for gas therapy and manganese ions for magnetic resonance imaging (MRI) and CDT. experiments validated the pH-responsiveness of MnS@BSA at pH 6.8 and both H S gas and •OH radicals were detected during its degradation. experiments showed efficiently tumor turn-on -weighted MRI, significantly suppressed tumor growth and greatly prolonged survival of tumor-bearing mice following intravenous administration of MnS@BSA. Our findings indicated that MnS@BSA nanotheranostics hold great potential for traceable H S gas therapy primed CDT of cancer.

Hydrogen sulfide (H₂S) is a unique gasotransmitter, with regulatory roles in the cardiovascular, nervous, and immune systems. Some of the vascular actions of H₂S (stimulation of angiogenesis, relaxation of vascular smooth muscle) resemble those of nitric oxide (NO). Although it was generally assumed that H₂S and NO exert their effects via separate pathways, the results of the current study show that H₂S and NO are mutually required to elicit angiogenesis and vasodilatation. Exposure of endothelial cells to H₂S increases intracellular cyclic guanosine 5'-monophosphate (cGMP) in a NO-dependent manner, and activated protein kinase G (PKG) and its downstream effector, the vasodilator-stimulated phosphoprotein (VASP). Inhibition of endothelial isoform of NO synthase (eNOS) or PKG-I abolishes the H₂S-stimulated angiogenic response, and attenuated H₂S-stimulated vasorelaxation, demonstrating the requirement of NO in vascular H₂S signaling. Conversely, silencing of the H₂S-producing enzyme cystathionme-γ-lyase abolishes NO-stimulated cGMP accumulation and angiogenesis and attenuates the acetylcholine-induced vasorelaxation, indicating a partial requirement of H₂S in the vascular activity of NO. The actions of H₂S and NO converge at cGMP; though H₂S does not directly activate soluble guanylyl cyclase, it maintains a tonic inhibitory effect on PDE5, thereby delaying the degradation of cGMP. H₂S also activates PI3K/Akt, and increases eNOS phosphorylation at its activating site S1177. The cooperative action of the two gasotransmitters on increasing and maintaining intracellular cGMP is essential for PKG activation and angiogenesis and vasorelaxation. H₂S-induced wound healing and microvessel growth in matrigel plugs is suppressed by pharmacological inhibition or genetic ablation of eNOS. Thus, NO and H₂S are mutually required for the physiological control of vascular function.

We investigated the physiological and biochemical mechanisms by which H 2 S mitigates the cadmium stress in rice. Results revealed that cadmium exposure resulted in growth inhibition and biomass reduction, which is correlated with the increased uptake of cadmium and depletion of the photosynthetic pigments, leaf water contents, essential minerals, water-soluble proteins and enzymatic and non-enzymatic antioxidants. Excessive cadmium also potentiated its toxicity by inducing oxidative stress, as evidenced by increased levels of superoxide, hydrogen peroxide, methylglyoxal and malondialdehyde. However, elevating endogenous H 2 S level improved physiological and biochemical attributes, which was clearly observed in the growth and phenotypes of H 2 S-treated rice plants under cadmium stress. H 2 S reduced cadmium-induced oxidative stress, particularly by enhancing redox status and the activities of reactive oxygen species and methylglyoxal detoxifying enzymes. Notably, H 2 S maintained cadmium and mineral homeostases in roots and leaves of cadmium-stressed plants. By contrast, adding H 2 S-scavenger hypotaurine abolished the beneficial effect of H 2 S, further strengthening the clear role of H 2 S in alleviating cadmium toxicity in rice. Collectively, our findings provide an insight into H 2 S-induced protective mechanisms of rice exposed to cadmium stress, thus proposing H 2 S as a potential candidate for managing toxicity of cadmium and perhaps other heavy metals, in rice and other crops.

Diabetic kidney disease develops in approximately 40% of diabetic patients and is a major cause of chronic kidney diseases (CKD) and end stage kidney disease (ESKD) worldwide. Hydrogen sulfide (H2S), the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO), is synthesized in nearly all organs, including the kidney. Though studies on H2S regulation of renal physiology and pathophysiology are still in its infancy, emerging evidence shows that H2S production by renal cells is reduced under disease states and H2S donors ameliorate kidney injury. Specifically, aberrant H2S level is implicated in various renal pathological conditions including diabetic nephropathy. This review presents the roles of H2S in diabetic renal disease and the underlying mechanisms for the protective effects of H2S against diabetic renal damage. H2S may serve as fundamental strategies to treat diabetic kidney disease. These H2S treatment modalities include precursors for H2S synthesis, H2S donors, and natural plant-derived compounds. Despite accumulating evidence from experimental studies suggests the potential role of the H2S signaling pathway in the treatment of diabetic nephropathy, these results need further clinical translation. Expanding understanding of H2S in the kidney may be vital to translate H2S to be a novel therapy for diabetic renal disease.

Key Points Hydrogen sulphide (H 2 S), together with nitric oxide and carbon monoxide, belongs to a family of labile biological mediators called gasotransmitters. H 2 S has long been known as a toxic gas emanating from sewers and as a by-product of industrial processes; however, the biological processes of sulphide and its metabolism and fate in biological systems is now beginning to be understood. H 2 S is synthesized endogenously in numerous mammalian tissues by two enzymes responsible for metabolizing L -cysteine — cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGS). CBS is the predominant H 2 S-generating enzyme in the brain and nervous system. CSE is mainly expressed in the liver and in the vascular and non-vascular smooth muscle. Other sources of H 2 S include enterobacterial flora and inorganic sources. H 2 S exerts numerous biological effects on various biological targets, leading to responses that range from cytotoxic effects (due to free radical and oxidant generation) to cytoprotective (antinecrotic or anti-apoptotic) actions. In particular, H 2 S has been specifically shown to exert a pharmacological effect on potassium-opened ATP (K ATP ) channels. These opposing effects have been demonstrated in various animal models. Inhibition of sulphide in animal models of haemorrhagic shock has been demonstrated to accelerate the recovery of mean arterial pressure. H 2 S can also induce a suspended-animated-like state in mice — whether this can be achieved in larger animals remains to be seen. Protection from lethal hypoxic insult, myocardial injury and inflammation has also been shown. The options that could be explored to utilize this knowledge for therapeutic purposes are discussed. Two main pathways are considered viable: the development of inhibitors of CBS or CSE, and the development of H 2 S or H 2 S-releasing compounds. In this rapidly emerging field, there are still many unknowns — including the relationship of H 2 S with the other two gasotransmitters — however, further studies are likely to yield a number of therapeutic possibilities, and early stage drug candidates are already in development. Hydrogen sulphide (H 2 S) is increasingly being recognized as an important signalling molecule in the cardiovascular and nervous systems. This article overviews the physiology and biochemistry of H 2 S, summarizes the effects of H 2 S inhibitors or H 2 S donors in animal models of disease and discusses the likely options and paths for the therapeutic exploitation of H 2 S. Hydrogen sulphide (H 2 S) is increasingly being recognized as an important signalling molecule in the cardiovascular and nervous systems. The production of H 2 S from L -cysteine is catalysed primarily by two enzymes, cystathionine γ-lyase and cystathionine β-synthase. Evidence is accumulating to demonstrate that inhibitors of H 2 S production or therapeutic H 2 S donor compounds exert significant effects in various animal models of inflammation, reperfusion injury and circulatory shock. H 2 S can also induce a reversible state of hypothermia and suspended-animation-like state in rodents. This article overviews the physiology and biochemistry of H 2 S, summarizes the effects of H 2 S inhibitors or H 2 S donors in animal models of disease and outlines the potential options for the therapeutic exploitation of H 2 S.

Previous studies have demonstrated that hydrogen sulfide (H ₂S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO). H ₂S therapy also has been shown to augment NO bioavailability and signaling. The purpose of this study was to investigate the impact of H ₂S deficiency on endothelial NO synthase (eNOS) function, NO production, and ischemia/reperfusion (I/R) injury. We found that mice lacking the H ₂S-producing enzyme cystathionine γ-lyase (CSE) exhibit elevated oxidative stress, dysfunctional eNOS, diminished NO levels, and exacerbated myocardial and hepatic I/R injury. In CSE KO mice, acute H ₂S therapy restored eNOS function and NO bioavailability and attenuated I/R injury. In addition, we found that H ₂S therapy fails to protect against I/R in eNOS phosphomutant mice (S1179A). Our results suggest that H ₂S-mediated cytoprotective signaling in the setting of I/R injury is dependent in large part on eNOS activation and NO generation.

• Hydrogen sulphide (H₂S) has been proposed as the third gasotransmitter. In animal cells, H₂S has been implicated in several physiological processes. H₂S is endogenously synthesized in both animals and plants by enzymes with l‐Cys desulphydrase activity in the conversion of l‐Cys to H₂S, pyruvate and ammonia. • The participation of H₂S in both stomatal movement regulation and abscisic acid (ABA)‐dependent induction of stomatal closure was studied in epidermal strips of three plant species (Vicia faba, Arabidopsis thaliana and Impatiens walleriana). The effect of H₂S on stomatal movement was contrasted with leaf relative water content (RWC) measurements of whole plants subjected to water stress. • In this work we report that exogenous H₂S induces stomatal closure and this effect is impaired by the ATP‐binding cassette (ABC) transporter inhibitor glibenclamide; scavenging H₂S or inhibition of the enzyme responsible for endogenous H₂S synthesis partially blocks ABA‐dependent stomatal closure; and H₂S treatment increases RWC and protects plants against drought stress. • Our results indicate that H₂S induces stomatal closure and participates in ABA‐dependent signalling, possibly through the regulation of ABC transporters in guard cells.

Although many types of ancient bacteria and archea rely on hydrogen sulfide (H2S) for their energy production, eukaryotes generate ATP in an oxygen-dependent fashion. We hypothesize that endogenous H2S remains a regulator of energy production in mammalian cells under stress conditions, which enables the body to cope with energy demand when oxygen supply is insufficient. Cystathionine γ-lyase (CSE) is a major H2S-producing enzyme in the cardiovascular system that uses cysteine as the main substrate. Here we show that CSE is localized only in the cytosol, not in mitochondria, of vascular smooth-muscle cells (SMCs) under resting conditions, revealed by Western blot analysis and confocal microscopy of SMCs transfected with GFP-tagged CSE plasmid. After SMCs were exposed to A23187, thapsigargin, or tunicamycin, intracellular calcium level was increased, and CSE translocated from the cytosol to mitochondria. CSE was coimmunoprecipitated with translocase of the outer membrane 20 (Tom20) in mitochondrial membrane. Tom20 siRNA significantly inhibited mitochondrial translocation of CSE and mitochondrial H2S production. The cysteine level inside mitochondria is approximately three times that in the cytosol. Translocation of CSE to mitochondria metabolized cysteine, produced H2S inside mitochondria, and increased ATP production. Inhibition of CSE activity reversed A23187-stimulated mitochondrial ATP production. H2S improved mitochondrial ATP production in SMCs with hypoxia, which alone decreased ATP production. These results suggest that translocation of CSE to mitochondria on specific stress stimulations is a unique mechanism to promote H2S production inside mitochondria, which subsequently sustains mitochondrial ATP production under hypoxic conditions.