Sulfide Salts Research Articles

Use of a Near Infrared Probe to Assess Intracellular Hydrogen Sulfide Production

Abstract Hydrogen sulfide (H2S) is a ubiquitous gas and has been recently identified as the third biological gasotransmitter, along with the more well studied nitric oxide (NO) and carbon monoxide (CO). Intensive studies on its potential as a therapeutic agent for cardiovascular, inflammatory, infectious, and neuropathological diseases have been undertaken. Numerous studies have shown that H2S can regulate PI3K/AKT, NF-κB and MAPK signaling pathways, suppressing LPS-induced inflammation. However, its use in the clinical setting and mechanistic studies are limited in part due to the lack of effective H2S detection methods. In the current study, we investigated a compound as a potential near infrared (NIR-HS) probe to measure intracellular H2S. After being synthesized and purified using chromatography, NIR-HS probe was added to a cell-free environments in the presence of hydrogen sulfide salts (Na2S and NaHS) or a H2S-slow-releasing donor (GYY4137) to determine its ability in detecting H2S. We further demonstrated that the NIR-HS probe can detect endogenous H2S in different cell lines. Detected by using the NIR-HS probe, knocking down and overexpressing the endogenous H2S synthases (CBS, CTH, and MPST) altered the production of H2S, respectively. Further studies are needed to demonstrate its use in large scale and in vivo environment to further demonstrate its effectiveness in detecting H2S.

Achieving partial nitrification by harnessing basic hydrolysis of sulphide salts amid high dissolved oxygen conditions

Attempts are going on to incorporate sulphur into the carbon and nitrogen removal processes at a biological wastewater treatment plant by external dosing or its intrinsic presence. A possible form of dosing sulphide at the field scale is the external dosing as the sodium salt of sulphide which under basic hydrolysis increases the pH. We demonstrated that the sodium salt dosage of sulphide can also be useful in achieving partial nitrification (PN). The results showed that 15 mgS/L of the sodium salt of sulphide was sufficient to establish PN in the low-strength synthetic and real wastewater under adequate dissolved oxygen concentrations (1.3 ± 0.4 mg/L during discharge phase of SBR cycle to 5.3 ± 0.2 mg/L during aeration phase of SBR cycle). PN was achieved only during the operational phases when the pH rise due to the basic hydrolysis of sodium sulphide was not controlled. The dosage of sulphide as its sodium salt has dual advantages as an inhibitor to nitrite oxidising bacteria (NOB). The activity of NOBs was 10–20 mgN/gVSS/d during the operational phases when PN was effective. The long-term operation showed a nitrite accumulation ratio of 70 ± 19% with an effluent ammonia concentration of 19 ± 4 mgN/L and nitrite concentrations of 18 ± 4 mgN/L. At the genus level, the NOB communities Nitrospira and Nitrobacter diminished in the long-term phases of stable PN with real wastewater. NOB communities evolved again when sulphide dosage was stopped indicating this strategy needs to be adopted continuously to achieve PN not time-based. The study demonstrated a strategy to achieve the feasibility of sulfide-driven PN systems and has a potential application in nitrogen removal from domestic wastewater.

A growth chamber for chronic exposure of mammalian cells to H2S

H2S is a redox-active signaling molecule that exerts an array of cellular and physiological effects. While intracellular H2S concentrations are estimated to be in the low nanomolar range, intestinal luminal concentrations can be significantly higher due to microbial metabolism. Studies assessing H2S effects are typically conducted with a bolus treatment with sulfide salts or slow releasing sulfide donors, which are limited by the volatility of H2S, and by potential off-target effects of the donor molecules. To address these limitations, we describe the design and performance of a mammalian cell culture incubator for sustained exposure to 20–500 ppm H2S (corresponding to a dissolved sulfide concentrations of ∼4–120 μM in the cell culture medium). We report that colorectal adenocarcinoma HT29 cells tolerate prolonged exposure to H2S with no effect on cell viability after 24 h although ≥50 ppm H2S (∼10 μM) restricts cell proliferation. Even the lowest concentration of H2S used in this study (i.e. ∼4 μM) significantly enhanced glucose consumption and lactate production, revealing a much lower threshold for impacting cellular energy metabolism and activating aerobic glycolysis than has been previously appreciated from studies with bolus H2S treatment regimens.

Electrical properties of zinc sulfide and silver sulfide as binary salts in gel polymer electrolytes for quantum Dot-Sensitized solar cells

Gel polymer electrolytes (GPEs) with methyl cellulose (MC) polymer host have been prepared by solution casting. Succinonitrile (SN) is the plasticizer. ZnS and Ag2S are the sulfide salts added. The ZnS:Ag2S weight ratio has been varied. The crystallinity of MC:SN:co-ZnS-Ag2S:S has been investigated using X-ray Diffraction (XRD). The use of two cations from two different salts has decreased crystallinity of the GPEs and the. The MC:SN:(ZnS:Ag2S = 80:20):S GPE exhibited the lowest degree of crystallinity of 21.18 %. Ionic conductivity and dielectric studies have been studied using electrochemical impedance spectroscopy (EIS). MC:SN:(ZnS:Ag2S = 80:20):S electrolyte demonstrated the highest ionic conductivity at room temperature. The value is 6.93 × 10-2S.cm−1. The activation energy is 0.23 eV. The cell FTO/ZnOFe2O4/CdS/MC:SN:(ZnS:Ag2S = 80:20):S/GPE/Pt/FTO has been assembled and characterized. The efficiency obtained is 0.58 % with short current density (Jsc) of 2.15 mA.cm−2, open circuit voltage (Voc) of 0.48 V and fill factor (FF) of 0.56.

Utilization of lead–zinc mine tailings as cement substitutes in concrete construction: Effect of sulfide content

Production of acid mine drainage and emission of heavy metals from tailings, especially sulfide tailings, to the environment is one of the serious challenges in the management of mine tailings. The use of cementation process and replacement of cement with mine tailings in the manufacture of concrete is one of the practical approaches to the management of mine tailings. In this study, two different lead-zinc mine tailings (T1 with 0.4% and T2 with 19% sulfide content) were separately used as a cement substitution in concrete construction. Toxicity characteristic leaching procedure (TCLP), acid generation potential, compressive strength tests, and mercury intrusion porosimetry (MIP) were conducted on the constructed concrete samples. The TCLP test results revealed that with increasing the curing time of the samples, the leaching rate of toxic metals (arsenic, cadmium, chromium, cobalt, nickel, copper, zinc, and lead) in all samples was reduced to lower than the permissible criteria, indicating the good stabilization of heavy metals in concrete samples. The MIP test results also revealed that with increasing the curing days and subsequently the hydration process, the intruded mercury volume decreased, indicating that heavy metals were stabilized in concrete samples. The compressive strength test findings revealed that in constructed concrete containing 20% cement-replacing T1, with increasing the curing time of the sample from 28 to 90 days, the compressive strength increased from 16.9 to 19.8 MPa, and the leaching rate of heavy metals decreased from 39.64 to 23.65 μg/L,. In addition, in the sample with 20% T2, the compressive strength increased from 10.59 to 16.4 MPa, and the leaching rate of heavy metals decreased from 44.65 to 26.5 μg/L. Comparing the Scanning Electron Microscope (SEM) and Energy Dispersive X-ray analyzer (EDX) results, it was found that the Ca/Si ratio was lower in the samples prepared with mine tailings compared to the control, indicating insufficient amount of calcium available to form the main hydration product (C–S–H). Therefore, less C–S–H gel was formed in these samples. Also, according to the elemental distribution analysis, it was revealed that other heavy metals were scattered throughout the concrete matrix and stabilized in the concrete structure by forming new compounds. In general, it could be concluded that cement replacement with lead-zinc mine tailings up to 20% without the use of any improvement technique may be possible. Further, the formation of hydration products affected by high sulfide content and causes the production of sulfide salts that attack the concrete sample over time, thereby reducing cementitious properties and strength.

Hydrogen Sulfide Biology and Its Role in Cancer.

Hydrogen sulfide (H2S) is an endogenous biologically active gas produced in mammalian tissues. It plays a very critical role in many pathophysiological processes in the body. It can be endogenously produced through many enzymes analogous to the cysteine family, while the exogenous source may involve inorganic sulfide salts. H2S has recently been well investigated with regard to the onset of various carcinogenic diseases such as lung, breast, ovaries, colon cancer, and neurodegenerative disorders. H2S is considered an oncogenic gas, and a potential therapeutic target for treating and diagnosing cancers, due to its role in mediating the development of tumorigenesis. Here in this review, an in-detail up-to-date explanation of the potential role of H2S in different malignancies has been reported. The study summarizes the synthesis of H2S, its roles, signaling routes, expressions, and H2S release in various malignancies. Considering the critical importance of this active biological molecule, we believe this review in this esteemed journal will highlight the oncogenic role of H2S in the scientific community.

Stable Electrode/Electrolyte Interface for High-Voltage NCM 523 Cathode Constructed by Synergistic Positive and Passive Approaches.

Increasing the working voltage of lithium-ion batteries (LIBs) is an efficient way to increase energy density. However, high voltage triggers excessive electrolyte decomposition at the electrode-electrolyte interfaces, where the electrochemical performance such as cyclic stability and rate capability is seriously deteriorated. A new synergistic positive and passive approach is proposed in this work to construct a stable electrode-electrolyte interface at high voltage. As a positive approach, inorganic lithium sulfide salt (Li2S) is used as an electrolyte additive to build a stable cathode electrolyte interface (CEI) at the LiNi0.5Co0.2Mn0.3O2 (NCM523) cathode surface. In a passive way, acetonitrile (AN) is applied as a solvent additive to suppress oxidative decomposition of a carbonate electrolyte via preferential solvation with a lithium ion. Because of the synergistic interaction between the positive and passive approaches, the cyclic stabilities of NCM523/Li cells improved with a tiny amount of Li2S (0.01 mg mL-1) and AN (0.5 vol %). The capacity retention increased to 80.74% after 200 cycles compared to the cells with the blank electrolyte (67.98%) and AN-containing electrolyte (75.8%). What is more, the capacity retention of the NCM523/graphite full cell is increased from 65 to 81% with the addition of the same amount of Li2S and AN after 180 cycles. The mechanism is revealed on the basis of the theoretical calculations and various characterizations. The products derived from the preferential adsorption and oxidation of Li2S on the surface of NCM523 effectively increase the content of inorganic ingredients. However, the presence of AN prevents oxidation of the solvent. This study provides new principle guiding studies on a high-voltage lithium-ion battery with excellent electrochemical performance.

Excellent flexible Tin Oxide-metal sulfide nanocomposites grown by spin coating chemical route

Tin oxide /Metal sulfide nanocomposites were synthesized using two step solution route. In the first step SnO2 gel were obtained followed by the next step of addition of precursor of cadmium and sulfide salts. Films were grown on cellulose flexible substrate using spin coating method. All the samples were analyzed using structural, morphological and optical characterizations. In X ray diffractograms, tetragonal rutile structure is observed with shift in peak towards lower angle due to tensile strain. SEM micrographs show that the ring like structure converted into flake like structures. AFM micrographs also confirm the ring like or porous film converted into flake. Photoluminescence spectra exhibits the intensity of SnO2-CdS decreases as compared to SnO2. Optical transmittance confirms the formation of nanocomposite due to additional band was observed in nanocomposites.

Stable Sodium Metal Anode Enabled by an Interface Protection Layer Rich in Organic Sulfide Salt.

Sodium (Na) metal is considered as a promising anode candidate for large-scale energy storage systems because of its high theoretical capacity and low electrochemical redox potential. However, Na anode suffers from a few challenges, such as the dendrite growth and severe parasitic reactions with electrolytes, which greatly hinder its practical applications. In this work, we demonstrate that an organosulfur compound additive (tetramethylthiuram disulfide) provides a facile and promising approach to overcome the above challenges in carbonate-based electrolytes. This unique organosulfur additive can in situ form a stable interfacial protection layer rich in organic sulfide salts on the sodium metal surface during cycling, leading to a stable stripping/plating cycling. Additionally, a cycling Coulombic efficiency of 94.25% is achieved, and the full battery using Prussian Blue as a cathode delivers a reversible capacity of 86.2 mAh g-1 with a capacity retention of 80% after 600 cycles at 4 C.

Surface-treated Cu2ZnSnS4 nanoflakes as Pt-free inexpensive and effective counter electrode in DSSC

Inexpensive semiconducting counter electrode (CE) was fabricated from copper zinc tin sulfide (CZTS) nanoflakes (NFs) through simple non-vacuum-based techniques. The kesterite CZTS NFs were synthesized by hot injection method using oleic acid as solvent. CZTS CE was prepared through solid-state ligand exchange method using ammonium sulfide salt ((NH4)2S) as the displacement ligand. Thin-film CZTS CE (on FTO substrate) was developed through inexpensive layer-by-layer (LbL) approach, without any post-treatment such as toxic sulfurization process. Hence, the fabrication of CZTS CE through this approach is scalable. The CZTS thin film showed NFs like morphology with higher surface area and achieved good electrocatalytic activity towards the reduction of iodide electrolyte. Two DSSCs using different CEs (CZTS NFs and Pt) were fabricated in separate cell structures in our laboratory. DSSC with CZTS NFs as CE showed the power conversion efficiency of 2.95% which is comparable to the DSSC with Pt (3.11%).

Hydrogen sulfide donors: Therapeutic potential in anti-atherosclerosis.

Atherosclerosis (AS), an important cause of high mortality of cardiovascular disease, involves numerous pathophysiological processes, including endothelial cell damage, oxidative stress, inflammation, lipid deposition, vascular smooth muscle proliferation and migration, macrophage-derived foam cell formation, and platelet aggregation, and seriously endangers human health and safe of life. Hydrogen sulfide (H2S) was discovered as the third gaseous signaling molecule following nitric oxide (NO) and carbon monoxide (CO), and has been proposed to exert potentially significant effects in many physiological processes, especially in atherosclerosis. Compelling evidence suggests that malfunction of CSE/H2S pathway and downregulation of endogenous H2S level contribute to the pathogenesis of atherosclerosis, whereas exogenous supplementation of H2S can ameliorate many of atherogenic processes. The current knowledge on the anti-atherogenic role of H2S comes from the use of H2S donors and CSE or CBS inhibitors, or another more accurate genetic technology, including gene knockout and gene therapy studies. Among them H2S releasing donors have vast therapeutic potential in anti-atherosclerosis and are promising as one of the clinical strategies for atherosclerosis treatment. Based on the recent studies on therapeutic effects and mechanisms of H2S donors, this review focuses on the most recent advances of therapeutic potential of H2S donors in anti-atherosclerosis, especially synthetic organic donors, because sulfide salts can release H2S rapidly and lead to various adverse effects. In addition, the future of this domain is prospected.

A green process for phosphorus recovery from spent LiFePO4 batteries by transformation of delithiated LiFePO4 crystal into NaFeS2

Recovery of high-content and valuable elements including phosphorus (P) is critical for recycling of spent LiFePO4 battery, but P recovery is challengeable due to the poor solubility of lithium phosphate and iron phosphate. This study compared two strategies to recover P by adopting sulfide salt to induce P dissolution, i.e., recovery of P directly from LiFePO4, and step-by-step recovery of Li then P. The results revealed that the second strategy was more efficient because of the higher recovering efficiency and selectivity. Accordingly, an acid-free process to recover P was successfully demonstrated. Li-recovery efficiency of 97.5 % was reached at a leaching time of 65 min, and nearly 100 % P-recovery efficiency was reached at 5 h. Mechanism analysis revealed that the transforming of delithiated LiFePO4 crystal to NaFeS2 was mainly responsible for P dissolution. Thermodynamic analysis and density functional theory calculation further proved the transformation reaction, and a stepwise-transformation mechanism was proposed. In addition, P was reclaimed in the form of soluble phosphate salts. The process is especially appealing due to its environmental and economic benefits for recycling spent LiFePO4 batteries.

Biological Effects of Morpholin-4-Ium 4 Methoxyphenyl (Morpholino) Phosphinodithioate and Other Phosphorothioate-Based Hydrogen Sulfide Donors.

Significance: Hydrogen sulfide (H2S) is regarded as the third gasotransmitter along with nitric oxide and carbon monoxide. Extensive studies have demonstrated a variety of biological roles for H2S in neurophysiology, cardiovascular disease, endocrine regulation, and other physiological and pathological processes. Recent Advances: Novel H2S donors have proved useful in understanding the biological functions of H2S, with morpholin-4-ium 4 methoxyphenyl (morpholino) phosphinodithioate (GYY4137) being one of the most common pharmacological tools used. One advantage of GYY4137 over sulfide salts is its ability to release H2S in a slow and sustained manner akin to endogenous H2S production, rather than the delivery of H2S as a single concentrated burst. Critical Issues: Here, we summarize recent progress made in the characterization of the biological activities and pharmacological effects of GYY4137 in a range of in vitro and in vivo systems. Recent developments in the structural modification of GYY4137 to generate new compounds and their biological effects are also discussed. Future Directions: Slow-releasing H2S donor, GYY4137, and other phosphorothioate-based H2S donors are potent tools to study the biological functions of H2S. Despite recent progress, more work needs to be performed on these new compounds to unravel the mechanisms behind H2S release and pace of its discharge, as well as to define the effects of by-products of donors after H2S liberation. This will not only lead to better in-depth understanding of the biological effects of H2S but will also shed light on the future development of a new class of therapeutic agents with potential to treat a wide range of human diseases.

Ligand exchange in $$\hbox {Cu}_{2}\hbox {ZnSnS}_{4}$$ nanoparticles and its effect on counter electrode performance in dye-sensitized solar cells

Ligand-exchanged $$\hbox {Cu}_{2}\hbox {ZnSnS}_{4}$$ (CZTS) nanoparticles (NPs) were successfully synthesized from colloidal NPs by replacing the long chain organic ligand from the surface of NPs via a bi-phasic method. It was found that ammonium sulphide salt $$((\hbox {NH}_{4})_{2}\hbox {S})$$ plays a key role in changing the surface of the NPs from hydrophobic to hydrophilic. The efficacy of the ligand exchange process over the surface of the CZTS NPs was analysed using X-ray diffraction, Fourier transform infrared spectroscopy, ultraviolet–visible spectroscopy and scanning electron microscopy with energy dispersive X-ray. The ligand-exchanged CZTS NP-based counter electrodes (CEs) were fabricated by drop casting the inorganic ligand (ammonium sulphide)-capped CZTS nanoink onto the conducting substrate. Our result indicates that dye-sensitized solar cells (DSSCs) with inexpensive CZTS NP-based CEs show 2.42% efficiency. The present result indicates that CZTS CEs will be helpful as an alternative CE to a Pt CE in DSSC application.

A trisulfur radical anion (S3˙-) involved sulfur insertion reaction of 1,3-enynes: sulfide sources control chemoselective synthesis of 2,3,5-trisubstituted thiophenes and 3-thienyl disulfides.

Cascade cyclization reactions of S3˙-in situ generated from S2- with 1,3-enynes for the chemoselective synthesis of 2,3,5-trisubstituted thiophenes and 3-thienyl disulfides controlled by sulfide salts are developed. These two protocols provide new, environment-friendly and simple strategies to construct 2,3,5-trisubstituted thiophenes and 3-thienyl disulfides via the formation of two and six C-S bonds, respectively.

Pt decorated MoS2 nanoflakes for ultrasensitive resistive humidity sensor

In this work, we report the fabrication of a low power, humidity sensor where platinum nanoparticles (NPs) decorated few-layered molybdenum disulphide (MoS2) nanoflakes have been used as the sensing layer. A mixed solvent was used to exfoliate the nanoflakes from the bulk powder. Then the Pt/MoS2 composites were prepared by reducing Pt NPs from chloroplatinic acid hexahydrate using a novel reduction technique using sulphide salt. The successful reduction and composite preparation were confirmed using various material characterization tools like scanning electron microscopy, atomic force microscopy, transmission electron microscopy, x-ray diffraction, x-ray photoelectron spectroscopy, Raman spectroscopy and UV–visible spectroscopy. The humidity sensors were prepared by drop-coating the Pt-decorated MoS2 on gold interdigitated electrodes and then exposed to various levels of relative humidity (RH). Composites with different weight ratios of Pt were tested and the best response was shown by the Pt/MoS2 (0.25:1) sample with a record high response of ∼4000 times at 85% RH. The response and recovery times were ∼92 s and ∼154 s respectively with repeatable behaviour. The sensor performance was found to be stable when tested over a few months. The underlying sensing mechanisms along with detailed characterization of the various composites have been discussed.

The Drug Developments of Hydrogen Sulfide on Cardiovascular Disease.

The recognition of hydrogen sulfide (H2S) has been evolved from a toxic gas to a physiological mediator, exhibiting properties similar to NO and CO. On the one hand, H2S is produced from L-cysteine by enzymes of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3MST) in combination with aspartate aminotransferase (AAT) (also called as cysteine aminotransferase, CAT); on the other hand, H2S is produced from D-cysteine by enzymes of D-amino acid oxidase (DAO). Besides sulfide salt, several sulfide-releasing compounds have been synthesized, including organosulfur compounds, Lawesson's reagent and analogs, and plant-derived natural products. Based on garlic extractions, we synthesized S-propargyl-L-cysteine (SPRC) and its analogs to contribute our endeavors on drug development of sulfide-containing compounds. A multitude of evidences has presented H2S is widely involved in the roles of physiological and pathological process, including hypertension, atherosclerosis, angiogenesis, and myocardial infarcts. This review summarizes current sulfide compounds, available H2S measurements, and potential molecular mechanisms involved in cardioprotections to help researchers develop further applications and therapeutically drugs.

TİYOSÜLFAT LİÇİ: YÜKLÜ LİÇ ÇÖZELTİLERİNDEN ALTIN KAZANIMI VE ENDÜSTRİYEL UYGULAMALAR – BÖLÜM II

Düşük çevresel etki, yüksek seçimlilik ve hızlı liç kinetiği gibi avantajlara sahip olmasının anı sıra tiyosülfat liçi; belirli refrakter cevherlerden altın kazanımında da yüksek performans östermektedir. Ancak, tiyosülfat liçinin ticarileşememesinin önündeki önemli engellerin başında karmaşık liç kimyası ve çözelti saflaştırma/metal kazanımı aşamasında yüksek etkinlikte uygun ir yöntem geliştirilememiş olması gelmektedir. Bu çalışmada, yüklü tiyosülfat çözeltilerinden altın kazanımı için önerilen mevcut yöntemler ve bu yöntemlerin avantaj/dezavantajları irdelenmiştir. Sülfür tuzlarıyla çöktürme ve sementasyon yöntemlerinin uygulandığı pilot ölçekli tesislerin akım şemaları uygulama koşulları ile beraber sunulmuştur. Tiyosülfat liçinin (liç içinde reçine (iyon değişimi) + elektro-kazanım) ticari/endüstriyel ilk ve tek uygulaması olan ve 2015 yılında Barrick Gold şirketi tarafından refrakter bir altın cevheri için geliştirilen prosesin özellikleri akım şeması ile birlikte açıklanmıştır. Prosesteki önemli teknik zorlukların başında reçineden metallerin sıyırma işlemi gelmektedir. Tiyosülfat liçinin endüstriyel olarak yaygınlaşabilmesi için daha etkin ve ekonomik çözelti saflaştırma/metal kazanımı tekniklerinin geliştirilmesi önem arz etmektedir.

228 - Evaluation of a Novel Mitochondria-targeted Peptide-based H2S Donor Compound (RTP-10) in Hyperglycaemia-induced Microvascular Endothelial Cell Dysfunction

An overproduction of mitochondrial reactive oxygen species (ROS) in endothelial cells, is a major contributor to vascular endothelial dysfunction (VED) and angiopathy in diabetes. Hyperglycaemia (HG) induces metabolic changes in mitochondria, notably superoxide production, membrane hyperpolarisation and loss of ATP synthesis. Supplementation of cells and diabetic animals with sources of hydrogen sulfide (H2S) such as crude sulfide salts (e.g. NaSH) or the slow-release compound GYY4137 have been shown to protect the vasculature from the detrimental effects of oxidative stress (e.g. in hypoxia/ischaemia-reperfusion injury, diabetic angiopathy, stroke etc). However, since the major intracellular effect of H2S is on mitochondria (e.g. stimulation of cellular bioenergetics) massive concentrations (e.g. >200 µM) or doses in vivo (e.g. up to 1 g/kg for GYY4137) are required for this vascular protection as these approaches do not target H2S to where it is needed, i.e. the mitochondria. Two previously mitochondria-targeted H2S (mtH2SD) donor organic compounds based around a triphenylphosphonium (TPP+) targeting scaffold, AP39 and AP123 have been described in the literature which contain anethole dithiolethione and thiohydroxybenzamide as the H2S generating moieties. These compounds have shown significant efficacy when used therapeutically in several animal models of mitochondrial dysfunction at very low doses (7-300 µg / kg). Since the TPP+-based scaffolds require an active mitochondrial ΔΨm to accumulate within mitochondria, (a possible limitation) we now describe an alternative approach to target H2S to mitochondria using a novel H2S donor derivative of D-Arg-L-Tyr-L-Lys-L-Phe-NH2 (RTP10). We therefore exposed murine b.End3 brain microvascular endothelial cells to hyperglycaemia (HG) for 7 days to induce mitochondrial ‘stress’ and then added RTP10 (0.1 nM to 1 µM) for 3 days. After this time, the reversal of HG-induced metabolic changes, specifically mitochondrial ΔΨm (JC-1), mitochondrial superoxide, (mitosox) and ATP synthesis (by luminescence) were measured. RTP10 caused a concentration-dependent increase in mitochondrial H2S levels as well as reversed HG-induced mitochondrial hyperpolarisation and oxidant production, and restored ATP synthesis. Our study further suggests that targeting H2S to mitochondria may be a useful therapeutic strategy for reversing oxidative stress-induced mitochondrial damage in diabetes and other vascular and metabolic pathologies.

Recent Development of Hydrogen Sulfide Releasing/Stimulating Reagents and Their Potential Applications in Cancer and Glycometabolic Disorders.

As an important endogenous gaseous signaling molecule, hydrogen sulfide (H2S) exerts various effects in the body. A variety of pathological changes, such as cancer, glycometabolic disorders, and diabetes, are associated with altered endogenous levels of H2S, especially decreased. Therefore, the supplement of H2S is of great significance for the treatment of diseases containing the above pathological changes. At present, many efforts have been made to increase the in vivo levels of H2S by administration of gaseous H2S, simple inorganic sulfide salts, sophisticated synthetic slow-releasing controllable H2S donors or materials, and using H2S stimulating agents. In this article, we reviewed the recent development of H2S releasing/stimulating reagents and their potential applications in two common pathological processes including cancer and glycometabolic disorders.