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Determination of Sulfide in Brain Tissue by Gas Dialysis/Ion Chromatography: Postmortem Studies and Two Case Reports
Abstract
An analytical method for the determination of sulfide in human and rat brain is described. It utilizes a continuous flow gas dialysis pretreatment and quantitation by ion chromatography with electrochemical detection. Rat brain sulfide levels were reliably measured after fatal intoxication by intraperitoneal injection of NaHS. By expeditious analysis of samples it was possible to demonstrate the presence of endogenous levels of sulfide in both rat and human brain as well as to measure elevated brain levels of sulfide after intoxication. In postmortem rat brain tissue, elevated sulfide levels could still be reliably demonstrated 96 h after death if the bodies had been refrigerated at 4 degrees C. Two case studies of human hydrogen sulfide inhalation fatalities are presented. The described method was able to measure significantly elevated sulfide levels in both cases.
... The studies of Goodwin et al. described a very similar analytical technique to the above described chromatography for the determination of sulfide in human and rat brain tissue with a detection range of 100 μM [41]. They used continuous flow gas dialysis as pre-treatment of the sample, followed by quantitation by ion chromatography with electrochemical detection. ...
... The studies of Goodwin et al. described a very similar analytical technique to the above described chromatography for the determination of sulfide in human and rat brain tissue with a detection range of 100 µM [41]. They used continuous flow gas dialysis as pre-treatment of the sample, followed by quantitation by ion chromatography with electrochemical detection. ...
... Therefore, it could be a promising technique for the post-mortem analysis of H 2 S concentrations in tissues from individuals who suffered from inhalation poisoning. Nevertheless, sample preparation is labor-intensive and quantification of H 2 S by this method requires specialized instrumentation [41]. ...
Hydrogen sulfide (H2S) is a gasotransmitter and the smallest signaling thiol metabolite with important roles in human health. The turnover of H2S in humans is mainly governed by enzymes of sulfur amino acid metabolism and also by the microbiome. As is the case with other small signaling molecules, disease-promoting effects of H2S largely depend on its concentration and compartmentalization. Genetic defects that impair the biogenesis and catabolism of H2S have been described; however, a gap in knowledge remains concerning physiological steady-state concentrations of H2S and their direct clinical implications. The small size and considerable reactivity of H2S renders its quantification in biological samples an experimental challenge. A compilation of methods currently employed to quantify H2S in biological specimens is provided in this review. Substantial discrepancy exists in the concentrations of H2S determined by different techniques. Available methodologies permit end-point measurement of H2S concentration, yet no definitive protocol exists for the continuous, real-time measurement of H2S produced by its enzymatic sources. We present a summary of available animal models, monogenic diseases that impair H2S metabolism in humans including structure-function relationships of pathogenic mutations, and discuss possible approaches to overcome current limitations of study.
... Hydrogen sulfide (H 2 S) has been known as a toxic gas for several centuries. The research on H 2 S mainly focused on understanding its toxicological profile until the late twentieth century when its pharmacological functions were discovered [1]. In the late 1980's and 1990's, pioneering work by several research groups led to the discovery of H 2 S as an endogenous gasotransmitter with pharmacological and physiological roles in the mammalian cells [1][2][3]. ...
... The research on H 2 S mainly focused on understanding its toxicological profile until the late twentieth century when its pharmacological functions were discovered [1]. In the late 1980's and 1990's, pioneering work by several research groups led to the discovery of H 2 S as an endogenous gasotransmitter with pharmacological and physiological roles in the mammalian cells [1][2][3]. Subsequent studies have also reported its roles in cytoprotection [4][5][6][7][8], neuroprotection [9,10], smooth muscle relaxation [11,12], vasorelaxation and regulation of blood pressure [12][13][14][15][16][17][18], anti-inflammation [5,[19][20][21][22][23][24], cellular respiration [25][26][27][28][29], etc. Owing to its critical role in mammalian pathophysiology, H 2 S has found applications in several conditions as a therapeutic molecule [30][31][32]. ...
Hydrogen sulfide (H 2 S) is a multifaceted gasotransmitter molecule which has potential applications in many pathological conditions including in lowering intraocular pressure and providing retinal neuroprotection. However, its unique physicochemical properties pose several challenges for developing its efficient and safe delivery method system. This study aims to overcome challenges related to H 2 S toxicity, gaseous nature, and narrow therapeutic concentrations range by developing polymeric microparticles to sustain the release of H 2 S for an extended period. Various formulation parameters and their interactions are quantitatively identified using Quality-by-Design (QbD) approach to optimize the microparticle-based H 2 S donor (HSD) delivery system. Microparticles were prepared using a solvent-evaporation coacervation process by using polycaprolactone (PCL), soy lecithin, dichloromethane, Na 2 S.9H 2 O, and silicone oil as polymer, surfactant, solvent, HSD, and dispersion medium, respectively. The microparticles were characterized for size, size distribution, entrapment efficiency, and H 2 S release profile. A Main Effects Screening (MES) and a Response Surface Design (RSD) model-based Box-Behnken Design (BBD) was developed to establish the relationship between critical process parameters (CPPs) and critical quality attributes (CQAs) qualitatively and quantitatively. The MES model identified polymer to drug ratio and dispersion medium quantity as significant CPPs among others, while the RSD model established their quantitative relationship. Finally, the target product performance was validated by comparing predicted and experimental outcomes. The QbD approach helped in achieving overall desired microparticle characteristics with fewer trials and provided a mathematical relationship between the CPPs and the CQAs useful for further manipulation and optimization of release profile up to at least 30 days.
Graphical Abstract
... The neurotoxic face of H 2 S is the "classical" one and often results in respiratory paralysis, probably caused by the inhibition of the brain stem neurons controlling respiration, as well as delirium, vertigo, comas, and even death. It has been and it still is considered a serious occupational hazard, and its toxicology has been extensively reviewed [38][39][40]. ...
... Between 1989 and 1990, when three independent groups [1,40,41] measured endogenous sulfide levels in animals and in the brain, their observations opened the possibility of considering H 2 S as a neuronal gas transmitter with de facto involvement in the brain's physiology and metabolism. In the CNS, H 2 S modulates the function of neurons in various brain regions, from the spinal cord to the cortical areas, facilitating, for example, long-term potentiation, or sustaining excitatory postsynaptic potentials [3]. ...
Ever since its presence was reported in the brain, the nature and role of hydrogen sulfide (H2S) in the Central Nervous System (CNS) have changed. Consequently, H2S has been elected as the third gas transmitter, along with carbon monoxide and nitric oxide, and a number of studies have focused on its neuromodulatory and protectant functions in physiological conditions. The research on H2S has highlighted its many facets in the periphery and in the CNS, and its role as a double-faced compound, switching from protective to toxic depending on its concentration. In this review, we will focus on the bell-shaped nature of H2S as an angiogenic factor and as a molecule released by glial cells (mainly astrocytes) and non-neuronal cells acting on the surrounding environment (paracrine) or on the releasing cells themselves (autocrine). Finally, we will discuss its role in Amyotrophic Lateral Sclerosis, a paradigm of a neurodegenerative disease.
... For this reason, the endogenous levels of free H 2 S with this method were over-estimated. Two other groups also measured H 2 S levels in the brains of humans and bovine with a similar method, which showed 50-160 µM [44,45]. ...
Hydrogen sulfide (H2S) and polysulfides (H2Sn, n ≥ 2) produced by enzymes play a role as signalling molecules regulating neurotransmission, vascular tone, cytoprotection, inflammation, oxygen sensing, and energy formation. H2Sn, which have additional sulfur atoms to H2S, and other S-sulfurated molecules such as cysteine persulfide and S-sulfurated cysteine residues of proteins, are produced by enzymes including 3-mercaptopyruvate sulfurtransferase (3MST). H2Sn are also generated by the chemical interaction of H2S with NO, or to a lesser extent with H2O2. S-sulfuration (S-sulfhydration) has been proposed as a mode of action of H2S and H2Sn to regulate the activity of target molecules. Recently, we found that H2S/H2S2 regulate the release of neurotransmitters, such as GABA, glutamate, and D-serine, a co-agonist of N-methyl-D-aspartate (NMDA) receptors. H2S facilitates the induction of hippocampal long-term potentiation, a synaptic model of memory formation, by enhancing the activity of NMDA receptors, while H2S2 achieves this by activating transient receptor potential ankyrin 1 (TRPA1) channels in astrocytes, potentially leading to the activation of nearby neurons. The recent findings show the other aspects of TRPA1 channels—that is, the regulation of the levels of sulfur-containing molecules and their metabolizing enzymes. Disturbance of the signalling by H2S/H2Sn has been demonstrated to be involved in various diseases, including cognitive and psychiatric diseases. The physiological and pathophysiological roles of these molecules will be discussed.
... Hydrogen sulfide (H 2 S) is a gaseous molecule that, for several decades, was considered highly toxic in higher concentrations because of its negative impacts on animals and plants. The first evidence regarding H 2 S in animal brain cells was provided by Goodwin et al. (1989). Thereafter, vast research was conducted on the potential biological roles of H 2 S in plants. ...
... In addition, chromatographic approaches for sulfide detection using flow gas dialysis coupled with electrochemical quantification by ion chromatography have been reported. 125,126 This method reports good recovery of sample (95−99%) and has been used to measure post-mortem sulfide levels in rat and human brain tissue, although the required gas dialysis pretreatment step increases the complexity of this approach. ...
Hydrogen sulfide (H2S) is an important biological mediator across all kingdoms of life and plays intertwined roles in various disciplines, ranging from geochemical cycles to industrial processes. A common need across these broad disciplines is the ability to detect and measure H2S in complex sample environments. This Perspective focuses on key advances and opportunities for H2S detection and quantification that are relevant to chemical biology. Specifically, we focus on methods for H2S detection and quantification most commonly used in biological samples, including activity-based H2S probes, the methylene blue assay, the monobromobimane assay, and H2S-sensitive electrode measurements. Our goal is to help simplify what at first may seem to be an overwhelming array of detection and measurement choices, to articulate the strengths and limitations of individual techniques, and to highlight key unmet needs and opportunities in the field.
... Hydrogen sulfide (H 2 S) is the third and most recently recognized member of the gasotransmitters family together with nitric oxide (NO) and carbon monoxide (CO). 1 H 2 S is endogenously synthesized by three different enzymes called cystathionine-gamma lyase (CSE), cystathioninebeta synthase (CBS), and 3-mercaptopyruvate sulfur transferase. 2 H 2 S production has been confirmed in the mouse brain cortex and in post-mortem material from the human brain stem 3,4 but the physiological role of the H 2 S producing enzymes in the mouse and human brain vasculature still remains to be fully understood. All three H 2 S-producing enzymes are expressed in the cardiovascular system, but CSE is the one mainly responsible for the majority of the endogenous H 2 S production in the vasculature. ...
Aim:
In extracerebral vascular beds cystathionine-gamma lyase (CSE) activity plays a vasodilatory role but the role of this hydrogen sulfide (H2 S) producing enzyme in the intracerebral arterioles remain poorly understood. We hypothesized a similar function in the intracerebral arterioles.
Methods:
Intracerebral arterioles were isolated from wild type C57BL/6J mouse (9-12 months old) brains and from human brain biopsies. The function (contractility and secondary dilatation) of the intracerebral arterioles was tested ex vivo by pressure myography using a perfusion set-up. Reverse transcription polymerase chain reaction was used for detecting CSE expression.
Results:
CSE is expressed in human and mouse intracerebral arterioles. CSE inhibition with L-propargylglycine (PAG) significantly dampened the K+ -induced vasoconstriction in intracerebral arterioles of both species (% of maximum contraction: in human control: 45.4 ± 2.7 versus PAG: 27 ± 5.2 and in mouse control: 50 ± 1.5 versus PAG: 33 ± 5.2) but did not affect the secondary dilatation. This effect of PAG was significantly reversed by the H2 S donor sodium hydrosulfide (NaSH) in human (PAG + NaSH: 38.8 ± 7.2) and mouse (PAG + NaSH: 41.7 ± 3.1) arterioles, respectively. The endothelial NO synthase (eNOS) inhibitor, Nω-Nitro-l-arginine methyl ester (L-NAME), and the inhibitor of soluble guanylate cyclase (sGC), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reversed the effect of PAG on the K+ -induced vasoconstriction in the mouse arterioles and attenuated the K+ -induced secondary dilatation significantly.
Conclusion:
CSE contributes to the K+ -induced vasoconstriction via a mechanism involving H2 S, eNOS, and sGC whereas the secondary dilatation is regulated by eNOS and sGC but not by CSE.
... Hydrogen sulfide (H 2 S) is the third gasotransmitter alongside nitric oxide (NO) and carbon monoxide (CO). [1][2][3][4][5][6] Since the detection of sulfide in brain tissues of rats in 1989, [7] H 2 S has been found to have many physiological functions, such as vasodilation, stimulation of cellular bioenergetics, antioxidation, anti-inflammation, and pro-angiogenesis. [1,[8][9][10][11][12] The biosynthesis of H 2 S has been characterized, including three enzymatic pathways involving cystathionine γ-lyase (CSE), cystathionine βsynthetase (CBS), and 3-mercaptopyruvate sulfurtransferase , as well as non-enzymatic pathways. ...
An expanding body of evidence suggests that specifically targeting hydrogen sulfide (H2S) might potentially benefit both tumor diagnosis and treatment, but there is still a lack of cancer‐targeted molecular tools for in vivo applications. Here, we report the first ligand‐directed H2S‐specific near‐infrared fluorescent sensor PSMA‐Cy7‐NBD and scavenger PSMA‐Py‐NBD that target the prostate‐specific membrane antigen (PSMA). PSMA‐Cy7‐NBD displays a 53‐fold off–on fluorescence response to H2S at 803 nm with high specificity. PSMA‐Py‐NBD can scavenge H2S fast (k2=30.8 M⁻¹ s⁻¹ at 25 °C) without interference from biothiols. Both tools are highly water‐soluble and can be transported selectively into PSMA‐expressing prostate cancer cells. Endogenous H2S levels in murine 22Rv1 tumor models can be imaged and downregulated by intravenous injection of PSMA‐Cy7‐NBD and PSMA‐Py‐NBD, respectively. These tools could potentially help to investigate H2S cancer biology and with related therapies.
... Disulfane (HSSH), trisulfane, (HSSSH) and their conjugate bases hydrodisulfide or disulfanide (HS 2 ‾) and hydrotrisulfide (HS 3 ‾), respectively, are the lower members of the family of polysulfanes (HSS n H, 1 ≤ n ≤ 34) [1][2][3], and have been recognized as endogenous diffusible species in different tissues [4][5][6][7][8][9]. These inorganic reactive sulfur species (RSS) appear as byproducts of the activity of the 3-mercaptopyruvate sulfuryl transferase, 3-MST, which canonically delivers hydrogen sulfide, H 2 S [10,11]. ...
The mechanism of the metal centered reduction of metmyoglobin (MbFeIII) by inorganic disulfide species has been studied by combined spectroscopic and kinetic analyses, under argon atmosphere. The process is kinetically characterized by biexponential time traces, for variable ratios of excess disulfide to protein, in the pH interval 6.6-8.0. Using UV-vis and resonance Raman spectroscopies, we observed that MbFeIII is converted into a low spin hexacoordinated ferric complex, tentatively assigned as MbFeIII(HSS-)/MbFeIII(SS2-), in an initial fast step. The complex is slowly converted into a pentacoordinated ferrous form, assigned as MbFeII according to the resonance Raman records. The reduction is a pH-dependent process, but independent of the initial disulfide concentration, suggesting the unimolecular decomposition of the intermediate complex following a reductive homolysis. We estimated the rate of the fast formation of the complex at pH 7.4 (kon = 3.7 × 103 M-1 s-1), and a pKa2 = 7.5 for the equilibrium MbFeIII(HSS-)/MbFeIII(SS2-). Also, we estimated the rate for the slow reduction at the same pH (kred = 10-2 s-1). A reaction mechanism compliant with the experimental results is proposed. This mechanistic study provides a differential kinetic signature for the reactions of disulfide compared to sulfide species on metmyoglobin, which may be considered in other hemeprotein systems.
... These investigators further revealed the presence of endogenous sulfides in normal brains without the inhalation of H 2 S, suggesting for the first time a normal physiologic role for H 2 S in the brain. Additionally, around that same time, elevated sulfide levels were observed in the brain of two fatal cases of H 2 S poisoning, further generating recognition and interest in the role of H 2 S in the brain [9]. Taken together, the detection of sulfides in the brain spurred detailed studies that ultimately forged a new field of research into this ancient signaling molecule [10]. ...
The gaseous signaling molecule hydrogen sulfide (H2S) critically modulates a plethora of physiological processes across evolutionary boundaries. These include responses to stress and other neuromodulatory effects that are typically dysregulated in aging, disease, and injury. H2S has a particularly prominent role in modulating neuronal health and survival under both normal and pathologic conditions. Although toxic and even fatal at very high concentrations, emerging evidence has also revealed a pronounced neuroprotective role for lower doses of endogenously generated or exogenously administered H2S. Unlike traditional neurotransmitters, H2S is a gas and, therefore, is unable to be stored in vesicles for targeted delivery. Instead, it exerts its physiologic effects through the persulfidation/sulfhydration of target proteins on reactive cysteine residues. Here, we review the latest discoveries on the neuroprotective roles of H2S in Alzheimer’s disease (AD) and traumatic brain injury, which is one the greatest risk factors for AD.
... In blood, the concentration of H 2 S has been reported to be ranging from 30-100 μM. [32][33][34] The H 2 S concentrations within brain tissue, the aorta and other homogenized samples from specific regions, in which H 2 S may play significant roles, are higher than that within the blood, indicating that H 2 S is an autocrine and paracrine messenger. [35][36][37] Due to its volatile nature, the stabilization of H 2 S concentrations within in vitro experimentation is difficult because the equilibrium will shift to the left in the absence of glutathione, "sulfane sulfur" Wang, Q.; et al. ...
Hydrogen sulfide (H2S) has been reported as an endogenous gasotransmitter that contributes to the modulation of a myriad of biological signalling pathways, which includes maintaining homeostasis in living organisms at physiological concentrations, controlling protein sulfhydration and persulfidation for signalling processes, mediating neurodegeneration, and regulating inflammation and innate immunity, etc. As a result, researchers are actively exploring effective approaches to evaluate the properties and the distribution of H2S in vivo. Furthermore, the regulation of the physiological conditions of H2S in vivo introduces the opportunity to further study the molecular mechanisms by which H2S regulates cellular functions. In recent years, many H2S-releasing compounds and biomaterials that can deliver H2S to various body systems have been developed to provide sustained and stable H2S delivery. Additionally, various designs of these H2S-releasing biomaterials have been proposed to aid in the normal conduction of physiological processes, such as cardioprotection and wound healing, by modulating different signalling pathways and cell functionalities. Using biomaterials as a platform to control the delivery of H2S introduces the opportunity to fine tune the physiological concentration of H2S in vivo, a key to many therapeutic applications. In this review, we highlight recent research works concerning the development and application of H2S-releasing biomaterials with a special emphasis to different release triggering conditions in in vivo studies. We believe that the further exploration of the molecular mechanisms underlying H2S donors and their function when incorporated with various biomaterials will potentially help us understand the pathophysiological mechanisms of different diseases and assist the development of H2S-based therapies.
... Furthermore, recent evidence suggested that cancer cells also produced large amounts of H 2 S, and their invasions were dependent on the contents of H 2 S [5]. According to recent publications, the sulfide concentration in blood is in the range of 10-100 μM [6]. Abnormal amounts of H 2 S may lead to many different diseases, such as Down's syndrome [7,8], Alzheimer's disease [9], diabetes [10], liver cirrhosis and hypertension. ...
A supramolecular host-guest [2]pseudo-rotaxane polymer containing blue-emissive (λem = 425 nm) anthracene-based di-topic donor guest (AN-G) and green-emissive (λem = 530 nm) napthalimide-based di-topic acceptor host (NP–H) after hydrogen sulfide (HS⁻ anion) detection in semi-aqueous media was developed in this study. Towards HS⁻ detection, the bi-fluorophoric [2]pseudo-rotaxane polymer possessed the best FRET process in the THF/Water solution (60% H2O, v/v), which was confirmed by TRPL measurements with the shortest lifetime of 1.1 ns and FRET efficiency of 81.7% in comparison with the longer lifetime of 6.0 ns for mono-fluorophoric [2]pseudo-rotaxane polymer analogue before detection of HS⁻. The 1:1 host–guest molar ratio and the formation of the [2]pseudo-rotaxane polymer can be further verified using ¹H NMR complexation and DOSY experiments. The effects of pH and temperature were also investigated to find that an efficient FRET process of the host-guest could occur at lower and neutral pH values (i.e., pH = 1–9) and in the normal temperature range of 25–40 °C. As the napthalimide can react with HS⁻ anion to induce green turn-on emission behavior, the napthalimide-based mono-fluorophoric guest could detect HS⁻ anion by turn-on photoluminescence with a corresponding limit of detection (LOD) value of 1.04 μM, which was also confirmed to possess a very high selectivity of HS⁻ detection compared with another 23 analytes, including 16 anionic species. In contrast, the optimum LOD value of 0.30 μM for bi-fluorophoric host-guest polymer as a FRET-ON sensor material towards HS⁻ detection was achieved due to the ratiometric emission of distinct color change from blue donor to green acceptor. Therefore, host-guest [2]pseudo-rotaxane polymer can be employed for the future bio-imaging applications of HS⁻ anion detection in living cells.
... Moderated concentrations of H 2 S (10-160 μM) stimulate electron transport and mitochondrial ATP production. By contrast, high concentrations (>320 μM) inhibit the cytochrome c oxidase irreversibly, preventing ATP synthesis and impairing oxygen transport in cardiomyocytes and colonocytes (Szabo et al., 2014;Ł owicka and Be ł towski, 2007), leading to cell death (Szabo et al., 2014;Goodwin et al., 1989). ...
Hydrogen sulfide (H2S) has been known for its toxicity. However, recent studies have focused on the mechanisms involved in endogenous production and function. To date, the H2S role in insulin signaling and glucose homeostasis is unclear. This uncertainty is even more evident in skeletal muscle, a physiological niche highly relevant for regulating glycemia in response to insulin. This study aimed to investigate the role of H2S on insulin signaling and glucose uptake in the L6 skeletal muscle cell line. We evaluated the endogenous synthesis with the fluorescent dye, 7-azido-4-methyl coumarin (7-AzMC). Glucose restriction-induced an increase in the endogenous levels of H2S, likely through stimulation of cystathionine γ-lyase activity, as its specific inhibitor, PAG (5 mM) prevented this increase, and mRNA levels of CSE decreased with glucose and amino acid restriction. Exogenous H2S reduced insulin-induced glucose uptake at 0.5 up to 24 h, an effect dissociated from the level of Akt phosphorylation. Our results show that glucose restriction induces endogenous production of H2S via CSE. In addition, H2S disrupts insulin-induced glucose uptake independent of the Akt pathway. These results suggest that H2S antagonism over insulin-induced glucose uptake could help maintain the plasmatic glucose levels in conditions that provoke hypoglycemia, which could serve as an H2S-regulated mechanism for maintaining glucose plasmatic levels through the inhibition of the skeletal muscle insulin-depended glucose uptake.
... [1,2] However, exposure to high level of sulfide can cause suffocation, loss of consciousness, and even irritation of mucous membranes. [3,4] Consequently, hydrogen sulfide detection has attracted consideration in daily life. However, the aberrant levels of H 2 S can result in many health problems, including diabetes, atherosclerosis, stroke, Alzheimer's disease, diabetes, and cirrhosis of the liver. ...
A naphthol-functionalized bis(salamo)-like chromogenic and fluorogenic probe (TBS) was designed and synthesized for efficient double-channel detection of hydrogen sulfide (H2S). The probe TBS was characterized through various spectroscopic techniques. From both visible light and 365 nm UV light, TBS could have naked-eye recognition of H2S with obvious color change. In comparison with some chemical probes, the probe TBS could selectively monitor H2S with detection limit as low as 0.71 μM, which could serve as a promising candidate for detecting H2S in real world sampling. Beyond that, the sensing mechanism toward H2S was fully validated by ¹H NMR, mass spectra (ESI-MS) as well as UV titration. Density-functional theory and time-dependent density-functional theory calculations were also carried out to further explain the photophysical behavior of the probe TBS with H2S. Finally, the probe TBS could be utilized as sulfide-targeted probe in a practical sample.
... It is the third gas signaling molecule found in living organisms after CO and NO (Kabil et al. 2014). H 2 S was first discovered in the rat brain in 1989, and its endogenous content was tested to reach 1. 6 μg·g −1 (Goodwin et al. 1989) can freely passthrough biofilms and participate in cell signal conduction (Zhao et al. 2020). It has obvious regulatory and protective effects on the central nervous system, blood vessels and kidneys of animals (Sparks et al. 2014;Raiamanickam and Jinsong 2011). ...
Hydrogen sulfide (H 2 S) is the third gas signal molecule after nitrogen dioxide and carbon monoxide. It participates in many important daily activities in plants and can promote plant seed germination, photosynthesis and organic matter accumulation , pore movement, side rooting and delaying plant aging. In recent years, studies have shown that H 2 S plays an important role in plant resistance to biological and abiotic stress. This article introduces the anabolic pathway of H 2 S in plants and the important functions of H 2 S in relieving plant stress from heavy metals, high salinity, low oxygen, drought, high and low temperature, and summarizes the research advances on the mechanism of resistance. At the same time, the interaction and the potential molecular mechanism between H 2 S and other signaling molecules are discussed, which should provide a theoretical reference for future in-depth research on the mechanism of action of H 2 S.
... It is the third gas signaling molecule found in living organisms after CO and NO (Kabil et al. 2014). H 2 S was first discovered in the rat brain in 1989, and its endogenous content was tested to reach 1. 6 μg·g −1 (Goodwin et al. 1989) can freely passthrough biofilms and participate in cell signal conduction (Zhao et al. 2020). It has obvious regulatory and protective effects on the central nervous system, blood vessels and kidneys of animals (Sparks et al. 2014;Raiamanickam and Jinsong 2011). ...
Hydrogen sulfide (H2S) is the third gas signal molecule after nitrogen dioxide and carbon monoxide. It participates in many
important daily activities in plants and can promote plant seed germination, photosynthesis and organic matter accumulation, pore movement, side rooting and delaying plant aging. In recent years, studies have shown that H2S plays an important
role in plant resistance to biological and abiotic stress. This article introduces the anabolic pathway of H2S in plants and
the important functions of H2S in relieving plant stress from heavy metals, high salinity, low oxygen, drought, high and
low temperature, and summarizes the research advances on the mechanism of resistance. At the same time, the interaction
and the potential molecular mechanism between H2S and other signaling molecules are discussed, which should provide a
theoretical reference for future in-depth research on the mechanism of action of H2S.
... 13 H 2 S has been regarded for a long time as a metabolic waste. 18,19 It was not until quite recently did researchers start to realize that H 2 S is an important endogenous gas signaling molecule, which plays important roles in a wide range of physiological and pathological conditions in various types of cells. 8 In this study, H 2 S was generated by NaHS, a dependable source to boost H 2 S concentrations. ...
Objective
Hydrogen sulfide (H2S) has been found to act as an important gasotransmitter to regulate cell activities. This study aimed to investigate the effect of H2S on autophagy of nucleus pulposus (NP) cells under hypoxia and possible mechanism.
Materials and Methods
NP cells were isolated from rat caudal discs. Cobalt chloride was used to mimic hypoxia, sodium hydrosulfide was used to emulate exogenous H2S and 3-methyladenine was used to block cell autophagy. Cell viability was assessed by phase contrast microscope and Cell Counting Kit-8 method. Moreover, expression of key autophagic proteins was analyzed via western blotting, and transmission electron microscopy was performed to detect autophagosomes.
Results
Hypoxia markedly impaired NP cell proliferation compared with control. Whereas H2S provided pro-proliferation and pro-autophagy effects on hypoxic NP cells. However, these beneficial impact of H2S on hypoxic NP cells were reversed by autophagy inhibitor.
Conclusions
Our results showed that H2S played a cytoprotective role in NP cells exposed to hypoxia in an autophagy-dependent manner.
... The gaseous molecule hydrogen sulphide (H 2 S) in higher concentrations was considered a toxin for decades due to its detrimental effect on plants and animals. Goodwin et al. (1989) provided the first report on the presence of H 2 S in animal brain tissues. Nonetheless, the first breakthrough in endogenous H 2 S was reported by Abe & Kimura (1996) as neuromodulator in the brain and, later, a H 2 S generating enzyme was identified (Zhao et al. 2001). ...
Hydrogen sulphide (H2S) is a gaseous molecule and originates endogenously in plants. It is considered a potential signalling agent in various physiological processes of plants. Numerous reports have examined the role of H2S in fruit ripening and in enhancing fruit quality traits. H2S coordinates the fruit antioxidant system, fruit ripening phytohormones, such as ethylene and abscisic acid, together with other ripening‐related signalling molecules, including nitric oxide and hydrogen peroxide. Although many studies have increased understanding of various aspects of this complex network, there is a gap in understanding crosstalk of H2S with key players of fruit ripening, postharvest senescence and fruit metabolism. This review focused on deciphering fruit H2S metabolism, signalling and its interaction with other ripening‐related signalling molecules during fruit ripening and postharvest storage. Moreover, we also discuss how H2S can be used as a tool for improving fruit quality and productivity and reducing postharvest loss of perishable fruits. Hydrogen sulphide modulates fruit antioxidant system and inhibits the ethylene biosynthesis and signaling to regulate fruit quality traits.
... It is also produced by microbes during microbial decomposition of organic waste under anaerobic conditions, such as in swamps and sewers (Salim et al. 2021). The initial concept of H 2 S as a toxic agent in biological systems was later refuted when it was discovered to be involved in signalling in brain cells of animals (Goodwin et al. 1989;Abe & Kimura, 1996). H 2 S emissions from leaves of several plant species were first observed by Wilson et al. (1978). ...
• Recent research focused on novel aspects of sulphur and sulphur-containing molecules in fundamental plant processes has highlighted the importance of these compounds. Currently, the focus has shifted to the efficacy of hydrogen sulphide (H2S) as signalling compounds that regulate different development and stress mitigation in plants.
• Accordingly, we used an in silico approach to study the differential expression patterns of H2S metabolic genes at different growth/development stages and their tissue-specific expression patterns under a range of abiotic stresses. Moreover, to understand the multilevel regulation of genes involved in H2S metabolism, we performed computation-based promoter analysis, alternative splice variant analysis, prediction of putative miRNA targets and co-expression network analysis.
• Gene expression analysis suggests that H2S biosynthesis is highly influenced by developmental and stress stimuli. The functional annotation of promoter structures reveales a wide range of plant hormone and stress responsive cis-regulatory elements (CREs) that regulate H2S metabolism. Co-expression analysis suggested that genes involved in H2S metabolism are also associated with different metabolic processes.
• In this data-mining study, the primary focus was to understand the genetic architecture governing pathways of H2S metabolism in different cell compartments under various developmental and stress signalling cascades. The present study will help to understand the genetic architecture of H2S metabolism via cysteine metabolism and the functional roles of these genes in development and stress tolerance mechanisms.
... Initially, it was mainly focused on its toxicology [2][3][4] and methods for separating it from gas mixtures [5]. The detection of endogenously produced H 2 S in the brain tissues of mammals in 1989 and the paper of Abe and Kimura suggesting that endogenous H 2 S plays a functional role in the regulation of neuronal function [6][7][8] redirected the research to the potential physiological and pathophysiological role of H 2 S. Currently, its therapeutic effects are recognized and exogenous H 2 S exerts cytoprotective and anticancer effects, promotes wound healing, inhibits platelet aggregation and protects against myocardial ischemia, among others [9,10]. However, the main challenge remains the effective exogenously delivery of H 2 S. The direct use of gas or sulphide salts has many drawbacks such as poor dose control leading to toxicity and difficulty in storing and handling gas at high pressures. ...
The search for H2S donors has been increasing due to the multiple therapeutic effects of the gas. However, the use of nanoporous materials has not been investigated despite their potential. Zeolites and activated carbons are known as good gas adsorbents and their modification with chitosan may increase the material biocompatibility and simultaneously its release time in aqueous solution, thus making them good H2S donors. Herein, we modified with chitosan a series of A zeolites (3A, 4A and 5A) with different pore sizes and an activated carbon obtained from glycerin. The amount of H2S adsorbed was evaluated by a volumetric method and their release capacity in aqueous solution was measured. These studies aimed to verify which of the materials had appropriate H2S adsorption/release properties to be considered a potential H2S donor. Additionally, cytotoxicity assays using HeLa cells were performed. Considering the obtained results, the chitosan composite with the A zeolite with the larger pore opening was the most promising material to be used as a H2S donor so a further cytotoxicity assay using H2S loaded was conducted and no toxicity was observed.
... Besides, H 2 S is also generated from D-cysteine by D-amino acid oxidase (DAO) (Wen et al., 2018). In the last several decades, the biological and pharmacological effects of H 2 S on various systems are gradually revealed after the measurement of brain H 2 S content in 1989 (Goodwin et al., 1989;Wang, 2002;Wang, 2012). Subsequently, H 2 S is emerging as an essential regulator in a diversity of physiological functions in the biological systems (Xie et al., 2016). ...
Cardiovascular diseases are the most common complications of diabetes, and diabetic cardiomyopathy is a major cause of people death in diabetes. Molecular, transcriptional, animal, and clinical studies have discovered numerous therapeutic targets or drugs for diabetic cardiomyopathy. Within this, hydrogen sulfide (H2S), an endogenous gasotransmitter alongside with nitric oxide (NO) and carbon monoxide (CO), is found to play a critical role in diabetic cardiomyopathy. Recently, the protective roles of H2S in diabetic cardiomyopathy have attracted enormous attention. In addition, H2S donors confer favorable effects in myocardial infarction, ischaemia-reperfusion injury, and heart failure under diabetic conditions. Further studies have disclosed that multiplex molecular mechanisms are responsible for the protective effects of H2S against diabetes-elicited cardiac injury, such as anti-oxidative, anti-apoptotic, anti-inflammatory, and anti-necrotic properties. In this review, we will summarize the current findings on H2S biology and pharmacology, especially focusing on the novel mechanisms of H2S-based protection against diabetic cardiomyopathy. Also, the potential roles of H2S in diabetes-aggravated ischaemia-reperfusion injury are discussed.
... Human and microbiota produce H 2 S through reverse trans-sulfuration and trans-sulfuration pathways, respectively, and use this gas molecule for their important physiological or biological functions. Basal levels of sulfide in rat and human brain tissues were detected about 30 years ago [13][14]. Clearly, thus detected sulfide was not the product of bacteria, neither the outcome of environmental intoxication. ...
Eukaryotes and microbiota produce H2S, using the same substrates and enzymes which constitute the reverse-trans-sulfuration and transsulfuration pathways. The homeostasis of gut microbiota impacts on the structural and functional integrity of gut epithelial barrier. Microbiota also serve as signalling sources to inform the host of the metabolism and functional changes. Microbiota dysbiosis negatively affect human health, contributing to diseases like obesity, diabetes, inflammatory bowel diseases, and asthma. Not by coincidence, these pathological conditions are also closely related to the abnormal metabolism and function of H2S signalling.H2S serves as a bacterial signal to the host and the host-produced H2S impacts on the population and size of microbiota. These bi-directional interactions become especially important for the digestion and utilization of sulfur amino acid in diet. Dietary restriction of sulfur amino acid increases the endogenous production of H2S by the host and consequently offers many health benefits. It, on the other hand, decreases the nutritional supply to the microbiota, which could be remedied by the co-application of prebiotics and probiotics. It is strategically sound to target the expression of H2S-producing enzymes in different organs to slow aging processes in our body and promote better health.
... It was not until the 1990s when endogenous and relatively high concentrations of hydrogen sulfide (H 2 S) were found in the brains of mice, humans, and cattle (1)(2)(3), that people's inherent perception of H 2 S as a toxic gas changed. Exogenous H 2 S is a strong neurotoxin with a sturdy stimulating effect on mucosa. ...
Hydrogen sulfide (H2S), as one of the three known gaseous signal transduction molecules in organisms, has attracted a surging amount of attention. H2S is involved in a variety of physiological and pathological processes in the body, such as dilating blood vessels (regulating blood pressure), protecting tissue from ischemia-reperfusion injury, anti-inflammation, carcinogenesis, or inhibition of cancer, as well as acting on the hypothalamus and pancreas to regulate hormonal metabolism. The change of H2S concentration is related to a variety of endocrine disorders, and the change of hormone concentration also affects the synthesis of H2S. Understanding the effect of biosynthesis and the concentration of H2S on the endocrine system is useful to develop drugs for the treatment of hypertension, diabetes, and other diseases.
... Hydrogen sul de (H 2 S) was thought as the third newest gaseous signal molecular, which was not only applied in animal and human physiological processes (such as dermatological diseases, cell behaviors, vascular system, neuronal disease, digestive systems, COVID-19 and so on) [5][6][7][8][9][10][11][12] , but also applied in agriculture 13 . A large number of studies in the eld of plants have shown that H 2 S can directly or indirectly involve in a wide range of plant physiological processes including stomatal movement 14 , photosynthesis 15 , seed germination 16 , root growth 17 , fruit ripening 18 , as well as plant senescence 19 . ...
The role of hydrogen sulfide (H 2 S) in regulating the pathogenic bacteria has been well documented. However, whether exogenous H 2 S addition inhibits the pathogens in soil is not understood, and whether H 2 S can suppress the plant disease caused by pathogen R. Solanacearum is not clear. In the present study, different concentrations of H 2 S donor NaHS were applied to the tobacco field to explore the interrelation among NaHS, tobacco baterial wilt, soil physicochemical properties and microbial community. In order to decipher the disease suppression mechanism from the perspective of soil microecology. Application of NaHS significantly reduced the disease incidence and disease index of TBW, increased soil pH, alkali-hydrolyzed nitrogen (AN), available phosphorus (AP), available phosphorus (AP) and organic matter (OM). NaHS addition also changed soil microbial community composition and structure. Furthermore, NaHS addition significantly reduced the abundance of Ralstonia and Fusarium , and increas pathogenic ed beneficial microorganisms S olirubrobacter , Rhodococcus , Rhizobium , Pseudomonas , Paenibacillus , Microvirga , Lysobacter , Haliangium , Granulicella , Flavobacterium , Bacillus , Trichoderma and Aspergillus at the genus level. Our findings suggested that exogenous application of NaHS significantly suppressed TBW caused by R. Solanacearum through regulated soil microecology. This study revealed the potential of NaHS in control of bacterial wilt.
Hydrogen sulfide (H2S) is a neuromodulator in the central nervous system. However, the physiological role of H2S in the nucleus ambiguus (NA) has rarely been reported. This research aimed to elucidate the role of H2S in the regulation of gastrointestinal motility in rats. Male 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 (PDTC, 4 nmol) + NaHS (4 nmol) group. Gastrointestinal motility curves before and after the injection were recorded using a latex balloon attached with a pressure transducer, which was introduced into the pylorus through gastric fundus. The results demonstrated that NaHS (4 and 8 nmol), an exogenous H2S donor, remarkably suppressed gastrointestinal motility in the NA of rats (P < 0.01). The suppressive effect of NaHS on gastrointestinal motility could be prevented by capsazepine, a transient receptor potential vanilloid 1 (TRPV1) antagonist, and PDTC, a NF-κB inhibitor. However, the same amount of PS did not induce significant changes in gastrointestinal motility (P > 0.05). Our findings indicate that NaHS within the NA can remarkably suppress gastrointestinal motility in rats, possibly through TRPV1 channels and NF-κB-dependent mechanism.
In this work, a hydrogel dressing for controlled release of hydrogen sulfide is developed for the repair of scalded wounds. It exhibits a responsive release of H 2 S based on ROS concentration, allowing precise modulation of the wound microenvironment.
Soon approaching its 50th anniversary, Journal of Analytical Toxicology (JAT) is an international scholarly publication specializing in analytical and forensic aspects of toxicology. Science Citation Index (SCI) and Journal Citation Reports (JCR), both of which are part of the Web-of-Science (WOS) database, were used to make a bibliometric evaluation of JAT articles. Between 1977 (volume 1) and 2023 (volume 47), a total of = n = 4,785 items were published in JAT; the top-ten most highly cited articles and the most prolific authors were identified. Changes in the journal impact factor (JIF) were studied between 1997 and 2022 and this metric varied from a low of 1.24 (2006) to a high of 3.36 (2020).The most recent JIF (2022) dropped to 2.5 and the corresponding 5-year JIF was 2.6. JAT’s most highly article (590 cites) was a working group (SWTOX) report dealing with methods recommended for the validation analytical methods used in forensic toxicology laboratories. JAT published 62 articles each of which were cited over 100 times and the H-index for JAT was 89. The most prolific author of JAT articles was credited with 119 items, the first in 1980 (volume 4) and the latest in 2023 (volume 47). JAT articles were cited 4,537 times in 2022 by all journals in the JCR database, although 520 of these were self-citations (11.5%). Bibliometric methods are increasingly used to evaluate the published work of individual scientists, university departments, entire universities, and whole countries. Highly cited articles are considered more influential and authoritative compared with papers that are seldom or never cited.
BODIPY derivatives have often been employed as fluorescent sensors to probe toxic ions in environment and living systems, such as sulfide ion (S2−). Whilst many structure modifications have been exploited on groups at the 3, 5, 8-positions, there are quite few examples on tailoring the 2,6-substituents for chemosensor investigations. Herein, we design and synthesize a 2,6-substituted BODIPY molecule, LM-BDP, to use as a fluorescent probe for detecting S2− in aqueous media. The electronic and crystal structures of the probe are studied by density functional theory (DFT) calculations and single-crystal X-ray diffraction analysis. Spectroscopy investigations are performed in a variety of conditions, showing that LM-BDP exhibits a noticeable color change from pink to dark red and a fluorescence shift from yellow to pink channel with decreased intensity upon addition of S2−. The selectivity and sensitivity measurements show that LM-BDP can only response to S2− with a detection limit of 0.29 μM in less than 100 s. The remarkable contrast in fluorescence images in test-stripe and RAW 264.7 cell experiments indicates that the probe is a proper candidate for the application in detecting exogenous S2−.
Since its discovery as a third unique gaseous signal molecule, hydrogen sulfide (H2S) has been extensively employed to resist stress and control pathogens. Nevertheless, whether H2S can prevent tobacco bacterial wilt is unknown yet. We evaluated the impacts of the H2S donor sodium hydrosulfide (NaHS) on the antibacterial activity, morphology, biofilm, and transcriptome of R. solanacearum to understand the effect and mechanism of NaHS on tobacco bacterial wilt. In vitro, NaHS significantly inhibited the growth of Ralstonia solanacearum and obviously altered its cell morphology. Additionally, NaHS significantly inhibited the biofilm formation and swarming motility of R. solanacearum, and reduced the population of R. solanacearum invading tobacco roots. In field experiments, the application of NaHS dramatically decreased the disease incidence and index of tobacco bacterial wilt, with a control efficiency of up to 89.49%. The application of NaHS also influenced the diversity and structure of the soil microbial community. Furthermore, NaHS markedly increased the relative abundances of beneficial microorganisms, which helps prevent tobacco bacterial wilt. These findings highlight NaHS's potential and efficacy as a powerful antibacterial agent for preventing tobacco bacterial wilt caused by R. solanacearum.
Hydrogen sulfide (H2S) is a unique signaling molecule that, along with carbon monoxide and nitric oxide, belongs to the gasotransmitters family. H2S is endogenously synthesized by enzymatic and non-enzymatic pathways. Three enzymatic pathways involving cystathionine-γ-lyase, cystathionine-β-synthetase, and 3-mercaptopyruvate sulfurtransferase are known as endogenous sources of H2S. This gaseous molecule has recently emerged as a regulator of many systems and physiological functions, including the cardiovascular system where it controls the vascular tone of small arteries. In this context, H2S leads to vasorelaxation by regulating the activity of vascular smooth muscle cells, endothelial cells, and perivascular nerves. Specifically, H2S modulates the functionality of different ion channels to inhibit the autonomic sympathetic outflow—by either central or peripheral mechanisms—or to stimulate perivascular sensory nerves. These mechanisms are particularly relevant for those pathological conditions associated with impaired neuromodulation of vascular tone. In this regard, exogenous H2S administration efficiently attenuates the increased activity of the sympathetic nervous system often seen in patients with certain pathologies. These effects of H2S on the autonomic sympathetic outflow will be the primary focus of this review. Thereafter, we will discuss the central and peripheral regulatory effects of H2S on vascular tone. Finally, we will provide the audience with a detailed summary of the current pathological implications of H2S modulation on the neural regulation of vascular tone.
It is crucial to monitor hydrogen sulfide (H2S) because H2S plays a vital role in the regulation of many physiology and pathology processes. Many evidences indicate that endogenous H2S is closely associated with many diseases such as inflammation and cancers. Herein, we reported a novel fluorescent probe BTDI to monitor the fluctuation of H2S based on the excited-state intramolecular proton transfer (ESIPT) mechanism both ex vivo and in vivo. The selectivity of BTDI for H2S is significantly higher than that for biothiols and other potential anions. After the probe responded to H2S, the nucleophilic addition reaction of the H2S with probe BTDI resulted the shifting of maximum emission peak from 630 nm to 542 nm and the fluorescent signals change from red to green emission along with a large Stokes shift (240 nm). Moreover, BTDI can be successfully applied to detect extracellular and endogenous H2S in living cells through fluorescent cell-imaging, which provides a promising tool for the specific recognition of H2S in complex biological systems.
Hydrogen sulfide (H2S) poisoning remains a significant source of occupational fatalities and is the second most common cause of toxic gas-induced deaths. It is a rapidly metabolized systemic toxicant targeting the mitochondria, among other organelles. Intoxication is mostly acute, but chronic or in-between exposure scenarios also occur. Some genetic defects in H2S metabolism lead to lethal chronic H2S poisoning. In acute exposures, the neural, respiratory, and cardiovascular systems are the primary target organs resulting in respiratory distress, convulsions, hypotension, and cardiac irregularities. Some survivors of acute poisoning develop long-term sequelae, particularly in the central nervous system. Currently, treatment for H2S poisoning is primarily supportive care as there are no FDA-approved drugs. Besides hyperbaric oxygen treatment, drugs in current use for the management of H2S poisoning are controversial. Novel potential drugs are under pre-clinical research development, most of which target binding the H2S. However, there is an acute need to discover new drugs to prevent and treat H2S poisoning, including reducing mortality and morbidity, preventing sequalae from acute exposures, and for treating cumulative pathology from chronic exposures. In this paper, we perform a comprehensive review of H2S poisoning including perspectives on past, present, and future.
Hydrogen sulfide (H 2 S) has been studied for over 250 years, and its role has expanded from that of a toxic gas to be the third important gasotransmitter. Historically, it has been challenging to accurately and reliably detect bioavailable sulfide in vivo or in vitro . We have studied and reported numerous aspects of the monobromobimane (MBB) method involving derivatization of bioavailable sulfide with excess MBB to produce sulfide‐dibimane (SDB). The resultant fluorescent SDB is measured by RP‐HPLC using fluorescence detector with the low limit of detection for SDB (2 nM) or by LC/MS allowing lower detection limits. This gold standard method can provide an acceptable measurement of bioavailable sulfide, which is a useful and powerful tool.
Hydrogen sulfide (H 2 S) and its oxidized products hydrogen polysulfides (H 2 S n , n ≥ 2) are signaling molecules regulating neurotransmission, vascular tone, cytoprotection, inflammation, oxygen sensing, energy formation, and so on. H 2 S is produced by cystathionine β‐synthase (CBS), cystathionine γ‐lyase (CSE), and 3‐mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase (CAT) from l ‐cysteine and 3MST together with d ‐amino acid oxidase (DAO) from d ‐cysteine. On the other hand, H 2 S n are produced by 3MST, sulfide‐quinone oxidoreductase (SQR), hemoglobin, neuroglobin, catalase, super oxide dismutase (SOD), and cysteine t‐RNA synthetase (CARS). These enzymes can also produce cysteine‐ and glutathione‐persulfide. The chemical interaction between H 2 S and NO also produces H 2 S n . H 2 S transmits signals by reducing cysteine disulfide as well as by S ‐sulfurating the S ‐nitrosylated and S ‐sulfenylated cysteine residues of target proteins to modify their activity, while H 2 S n S ‐sulfurates nonoxidized cysteine residues. H 2 S and H 2 S n interact with other signaling including NO, H 2 O 2 , and phosphorylation. This chapter focuses on the physiological roles of these molecules and the interaction with other signaling pathways.
Once considered solely to be a toxic molecule, it is now known that hydrogen sulfide (H 2 S) is also produced endogenously and participates in a multitude of physiological processes which include vasorelaxation, angiogenesis, response to stress, mitochondrial bioenergetics, and neuronal functions. H 2 S mediates most, if not all, of these functions through a post‐translational modification termed persulfidation/sulfhydration, which occurs on the –SH groups of reactive cysteine residues, converting them to persulfide or –SSH groups. H 2 S metabolism and sulfhydration are dysregulated during aging and neurodegeneration. In this chapter, we discuss the role of H 2 S in the brain, with a focus on Alzheimer's disease, the most common form of dementia worldwide and therapeutic opportunities pertaining to H 2 S metabolism.
Gasotransmitters have gained significant recognition attributed to their evident biological impacts, and is accepted as a promising and less-explored area with immense research scope. The three-member family comprising of nitric oxide, carbon monoxide and hydrogen sulphide as endogenous gaseous signaling molecules have been found to elicit a plethora of crucial biological functions, spawning a new research area. The sensing of these small molecules is vital to gain deeper insights into their functions, as they can act both as a friend or a foe in mammalian systems. The initial sections of the review present the physiological and pathophysiological roles of these endogenous gas transmitters and their synergistic interactions. Further, various detection approaches, especially the usage of fascinating features of 1,8-naphthalimide as fluorescent probe in the detection and monitoring of these small signaling molecules are highlighted. The current limitations and the future scope of improving the sensing of the three gasotransmitters are also discussed.
Oxygen and carbon dioxide are time honored gases that have direct bearing on almost all life forms, but over the past thirty years, and in large part due to the Nobel Prize Award in Medicine for the elucidation of nitric oxide (NO) as a bioactive gas, the research and medical communities now recognize other gases as critical for survival. In addition to NO, hydrogen sulfide (H2S) and carbon monoxide (CO) have emerged as a triumvirate or Trinacrium of gases with analogous importance and that serve important homeostatic functions. Perhaps, one of the most intriguing aspects of these gases is the functional interaction between them, which is intimately linked by the enzyme systems that produce them. Despite the need to better understand NO, H2S and CO biology, the notion that these are environmental pollutants remains ever present. For this reason, incorporating the concept of hormesis becomes imperative and must be included in discussions when considering developing new therapeutics that involve these gases. While there is now an enormous literature base for each of these gasotransmitters, we provide here an overview of their respective physiologic roles in the brain.
Glaucoma is an optic neuropathy disorder marked by progressive degeneration of the retinal ganglion cells (RGC). It is a leading cause of blindness worldwide, prevailing in around 2.2% of the global population. The hallmark of glaucoma, intraocular pressure (IOP), is governed by the aqueous humor dynamics which plays a crucial role in the pathophysiology of glaucoma. Glaucomatous eye has an IOP of more than 22 mmHg as compared to normotensive pressure of 10-21 mmHg. Currently used treatments focus on reducing the elevated IOP through use of classes of drugs that increase the aqueous humor outflow, decrease its production, or have multiple mechanisms. However, effective treatments should not only reduce IOP, but also offer neuroprotection and regeneration of RGCs. Hydrogen Sulfide (H2S), a gasotransmitter with several endogenous functions in mammalian tissues, is being investigated for its potential application in glaucoma. In addition to decreasing IOP by increasing aqueous humor outflow, it scavenges reactive oxygen species, upregulates the cellular antioxidant glutathione and protects RGCs from excitotoxicity. Despite the potential of H2S in glaucoma, its delivery to anterior and posterior region of the eye is a challenge due to its unique physicochemical properties. Firstly, development of any delivery system should not require an aqueous environment since H2S donors are susceptible to burst release of the gas in contact with water, causing potential toxicity and adverse effects owing to its inherent toxicity at higher concentrations. Secondly, the release of the gas from the donor needs to be sustained for a prolonged period of time for a dosing frequency as per the requirements of regulatory bodies. Lastly, the delivery system should provide adequate bioavailability throughout its period of application. Hence, an ideal delivery system should aim to tackle all the above challenges related to barriers of ocular delivery and physicochemical properties of H2S itself. This review discusses the therapeutic potential of H2S, its delivery challenges and strategies to overcome it.
Ever since the discovery of endogenous H2S and the identification of its cytoprotective properties, efforts have been made to develop strategies to use H2S as a therapeutic agent. The ability of H2S to regulate vascular tone, inflammation, oxidative stress, and apoptosis might be particularly useful in the therapeutic management of critical illness. However, neither the inhalation of gaseous H2S, nor the administration of inorganic H2S-releasing salts or slow-releasing H2S-donors are feasible for clinical use. Na2S2O3 is a clinically approved compound with a good safety profile and is able to release H2S, in particular under hypoxic conditions. Pre-clinical studies show promise for Na2S2O3 in the acute management of critical illness. A current clinical trial is investigating the therapeutic potential for Na2S2O3 in myocardial infarct. Pre-eclampsia and COVID-19 pneumonia might be relevant targets for future clinical trials.
Hydrogen sulfide (H2S) is associated with numerous psychological and pathological processes, and related closely with human health and diseases. The detection of H2S is a key to better understand its roles. In this paper, we developed a 4-phenylselenium coumarin (PhSeCou) as a rapid-response fluorescent probe for the selective and sensitive detection of H2S. The probe PhSeCou is a stable and almost non-fluorescentmolecule in a PBS buffer, and it can rapidly (< 60 s) sense H2S to give a strongly fluorescent product, Cou-H2S (Φf = 0.11, centred at 563 nm), thereby achieving to a sensitive detection at an ultra-low limit of detection (8.8 nM). The fluorescent probe displays a high selectivity for H2S over biothiols and other relevant analytes. What is more, through fluorescence cell-imaging, PhSeCou was successfully applied to detect exo- and endogenous H2S in living cells.
Hydrogen sulfide (H2S), is proposed as a cytoprotectant and gasotransmitter, involving in many physiological processes and regulating of some diseases. In physiological atmosphere, H2S is mainly existent in HS‐, which has a strong nucleophilicity and reducing potency. It also can precipitate with some metal ions forming metallic sulfides with high precipitation coefficient. In recent years, the researchers have a desire to develop methods to achieve real‐time detection of H2S in vivo, further understanding the physiology and pathology of H2S. In this minireview, we summarize recent progress for detecting of H2S in brain or cell and briefly expound the principle of methods with the comparison of the different methods between performance and temporal resolution.
Ruthenium(II) and iridium(III) coordination compounds display excellent structural, photophysical, and biological properties which make them highly promising as anticancer and bioimaging agents. When nanoparticles are functionalized with Ru(II) and Ir(III) complexes, enhanced performance and synergistic effects can be produced in the resultant nanosystems. This review begins by describing the three main strategies for the fabrication of Ru(II) and Ir(III) complex containing nanosystems. This is followed by a discussion of the ways in which Ru(II) and Ir(III) complexes and nanoparticles combine and interact to produce novel materials with efficacies exceeding the sum of their parts. The main body of the review then outlines the recent developments in Ru(II) and Ir(III) complex containing nanosystems for cancer treatment and bioimaging. To conclude, some of the future challenges and opportunities in this field are highlighted.
The physiological effects of the endogenously generated hydrogen sulfide (H2S) have been extensively studied in recent years. This review summarized the role of H2S in the origin of life and H2S metabolism in organisms from bacteria to vertebrates, examined the relationship between H2S and oxygen from an evolutionary perspective and emphasized the oxygen-dependent manner of H2S signaling in various physiological and pathological processes. H2S and oxygen are inextricably linked in various cellular functions. H2S is involved in aerobic respiration and stimulates oxidative phosphorylation and ATP production within the cell. Besides, H2S has protective effects on ischemia and reperfusion injury several organs by acting as an oxygen sensor. Also, emerging evidence suggests the role of H2S is in an oxygen-dependent manner. All these findings indicate the subtle relationship between H2S and oxygen and further explain why H2S, a toxic molecule thriving in an anoxia environment several billion years ago, still affects homeostasis today despite the very low content in the body.
The efficiency of energy transfer from guanine nucleotide to terbium ion (Tb³⁺) is affected by the phosphate group significantly. Compared with the biomolecules 5′-GMP (guanosine monophosphate), guanosine diphosphate (GDP) exhibits better sensitize ability to Tb³⁺ ions luminescence. Assisted with the carboxycoumarin ligand, we synthesized a more stable optical [email protected] polymer with the characteristic emission peaks located on 440 nm and 545 nm in this work. The [email protected] polymer is not only rich in metal binding sites, but also maintains a moderate ionic binding force, which helps metal ions to bind or leave it easily. Experiment result shows that [email protected] polymer has the appropriate binding force for Fe²⁺ ions, which can be destroyed by sulfur ions (S²⁻) as the formation of FeS precipitation. Based on this, [email protected] was designed as the ratio fluorescence probe for sulfur ions detection, where the fluorescence at 545 nm can be selectively quenched by Fe²⁺ ions, while that at 440 nm was unaffected, in the presence of S²⁻ ions, the quenched fluorescence can be recovered remarkably. With the increasing S²⁻ ions from 0.1–45 μM, the ratio of fluorescence intensity at 545 nm to 440 nm (F545/F440) is linear to S²⁻ concentration, and the detection limit of S²⁻ was calculated to be 0.073 μM. Contrast to those fluorescence probes with single wavelength emission, [email protected] displays a comparable sensitivity, the introduced self-adjust wavelength improved the detection accuracy efficiently. The above 98.1 % recovery rates of S²⁻ ions in the actual water sample demonstrated the practicability of [email protected] fluorescence probe.
We describe a method for the quantitative determination of cyanide and sulfide ions using specific ion electrodes in combination with Conway microdiffusion cells. The response of two types of electrodes to both ions in standard solutions is presented. The method is applicable to measurement of low to toxic concentrations of both ions in biologic specimens. Five autopsy cases with history of sudden death from noxious gases were studied using this technique, and high concentrations of sulfide ion (1,70 - 3.75 mg/L) were found in the blood samples.
The accuracy of the methylene blue colorimetric procedure for the determination of sulfide in environmental waters and waste waters is influenced by turbidity interferences even after application of recommended pretreatment techniques. The direct analysis of sulfide by ion chromatography (IC), without sample pretreatment, is complicated by field preservation of samples with zinc ion (or equivalent). A continuous-flow procedure has been developed that converts the acid-extractable sulfide to H/sub 2/S, which is separated from the sample matrix by a gas dialysis membrane and then trapped in a dilute sodium hydroxide solution. A 200-..mu..L portion of this solution is injected into the ion chromatograph for analysis with an electrochemical detector. Detection limits as low as 1.9 ng/mL have been obtained. Good agreement was found between the gas dialysis/IC and methylene blue methods for nonturbid standards. The addition of ascorbic acid as an antioxidant is required to obtain adequate recoveries from spiked tap and well waters.
Sulfur-deficient plant material may contain as little as 0.5 p.p.m. of sulfate sulfur. The soluble sulfate of soils giving rise to sulfur-deficient plants may be as low as 0.1 p.p.m. In studies of the sulfur nutrition of plants under conditions where growth is limited by their sulfur supply, often only small amounts of plant material are available for analysis. It was desirable to develop rapid and accurate methods for the determination of total sulfur and sulfate sulfur that would be relatively specific for sulfate sulfur in the presence of organic sulfur compounds. Sulfate is digested at 115° C. with a reducing mixture composed of hydriodic acid, formic acid, and red phosphorus. The resulting hydrogen sulfide is determined spectrophotometrically as methylene blue. From 1 to 300 micrograms of sulfate sulfur may be determined in 1 to 2 hours with a precision of 2 to 5% without interference in the presence of cystine, cysteine, glutathione, methionine, and taurine. Total sulfur may also be determined after the sample is ashed. The method permits rapid determination of sulfate sulfur or total sulfur in samples containing as little as 1 microgram of sulfur. It should prove of value in studies of sulfur metabolism in plant and animal biochemistry and physiology.
An improved procedure for the determination of sulfide using ion chromatography with electrochemical detection has been developed. Detection limits have been extended down to 0.1 ng/mL, with linear response up to 1000 ng/mL. Several factors affecting the response of the system to sulfide have been investigated, including condition of the columns, the arrangement of the columns, purity of reagents, composition of eluent, conditions of the working electrode, stability of sulfide solutions, mechanism of retention, and temperature of the systems. The two mains sources of error in the determination of sulfide are impurities in the eluent and adsorption of sulfide on the columns. Metal impurities in the eluent and on the column must be removed to achieve sensitivities below 20 ng/mL. To accomplish this, a new column cleaning procedure has been developed and a rearrangement in the positioning of the columns is recommended.
The nephrotoxic cysteine S-conjugate S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC) is metabolized by kidney homogenates and subcellular fractions to pyruvate and a reactive thiol, which is cytotoxic and partially decomposes to yield hydrogen sulfide and thiosulfate. Although hydrogen sulfide is a potent mitochondrial poison, the mitochondrial toxicity of CTFC is not attributable to hydrogen sulfide formation, as shown by different sites of inhibition of mitochondrial respiration by CTFC and hydrogen sulfide. The efficient mitochondrial oxidation of hydrogen sulfide apparently serves to protect mitochondria against the toxic effects of hydrogen sulfide generated from CTFC.
Ever since the role of the carotid bodies in controlling ventilation was elucidated by Heymans in 1932, researchers have puzzled over the seeming paradox presented by the action of hydrogen suifide gas on the nervous system. The dominant effect is depression of function, but the neural receptors of the carotids appear to be stimulated, resulting in hyperpnea at sublethal exposures. This paper examines the effect in light of the known cellular mechanisms of H,S poisoning, which inhibits the enzyme cytochrome oxidase, stopping oxidative metabolism. The argument is made that H,S affects the carotid sensors in the same manner as reduced oxygen tension, thus resulting in increased rate and depth of ventilation.
The workforce of Alberta, a province rich in fossil fuel, faces an increasing risk of exposure to hydrogen sulfide (H2S). Basic knowledge of the population exposed during the years 1969 to 1973 inclusive was accumulated to identify the immediate medical and management problems. Data were recorded from three sources of records: the Workers' Compensation Board of Alberta, the Alberta Hospital Services Commission and the provincial coroner's office. There were 221 cases of exposure to H2S. The overall mortality was 6%; 5% of victims were dead on arrival at hospital. Admission to hospital was required for 65% of the victims arriving at a hospital emergency room (78% of the 221). Acute problems were coma, dysequilibrium and respiratory insufficiency with pulmonary edema. Increased attention to cardiopulmonary resuscitation at the exposure site and during transportation to hospital is necessary to reduce the mortality from H2S exposure. No long-term adverse effects were apparent in the survivors.
Poisoning by hydrogen sulfide has been recognized as an occupational hazard for at least two centuries. The development of alternative sources of energy in North America may increase the incidence of this medical emergency in the future. Until recently, no specific antidote to sulfide was recognized. We have compared sulfide poisoning to cyanide poisoning and documented recent findings that indicate many similarities between the two. The therapeutic induction of methemoglobinemia, as by the intravenous administration of sodium nitrite, has both protective and antidotal effects against sulfide as well as against cyanide in laboratory animals. This procedure has been used successfully in at least one severe human case of sulfide poisoning. Industries at risk should be prepared to initiate this form of therapy in addition to the usual measures for cardiopulmonary resuscitation. No evidence exists to suggest that sulfide poisoning results in an impairment of the oxygen transport capability of blood. On the other hand, some victims of hydrogen sulfide poisoning exhibit frank cyanosis, suggesting that the respiratory tract obstruction is more common in this condition than is generally recognized. Suction of the upper tract and the administration of oxygen may be important ancillary procedures to the administration of sodium nitrite.
1. [ ³⁵ S]sulphate was used to obtain quantitative estimates of the transfer of sulphur between the blood, rumen and postruminal tract of four sheep given brome grass ( Bromus inermis ) pellets or lucerne ( Medicago sativa ) pellets at the rate of 33 or 66 g/h. Sodium sulphate (0–4 g S/d) was infused into the rumen or abomasum of sheep given brome grass during four periods of 19 d and was not infused into the sheep during a subsequent period in which lucerne was given. The flow of sulphide, sulphate, microbial S and non-microbial organic S from the abomasum was estimated using ¹⁰³ Ru and ⁵¹ Cr.
2. The concentration of inorganic sulphate in serum was increased to maximum values of 35–46 mg S/l by infusion of sulphate into the rumen or abomasum. The rate of irreversible loss of serum sulphate and rumen sulphide was positively related to the amount of sulphate infused.
3. Reabsorption of sulphate by the kidney reached a maximum of 0.69–1.1 mmol sulphate/l glomerular filtrate.
4. The transfer of sulphate from blood to the rumen was related to the concentration of inorganic sulphate in serum, attaining maximum values of 133 (±13) mg S/d for sheep given brome grass plus sulphate, and 127–159 mg S/d for sheep given lucerne.
5. Bacteria derived 0.52–0.67 of organic S from rumen sulphide in sheep given brome grass, and approximately 0.45 of bacterial organic S was derived from sulphide for sheep given lucerne. Protozoa derived approximately 0.90 of organic S from bacteria.
6. It was estimated that endogenous organic S contributed 300–340 mg S/d to the rumen, and that 0.24–0.45 of S digested in the rumen was derived from endogenous sources.
The acid-labile sulfide content of iron-sulfur proteins is commonly determined colorimetrically by reacting the released sulfide with N,N′-dimethyl-p-phenylenediamine and FeCl3, under acidic conditions, to form methylene blue. This reaction was found to be inhibited strongly when the iron-sulfur protein samples contained dithionite, which was frequently added during the purification of these proteins to prevent oxygen damage. The inhibitory substance(s) seems to be an anaerobic decomposition product(s) of dithionite. The use of concentrated protein solutions and small sample volumes was found to be the most effective way of overcoming this problem. This simple principle should also be useful when analyzing crude samples which may contain other low molecular weight, interfering substances.
The most commonly used method for labile sulfide determination in iron-sulfur proteins is the colorimetric procedure of Fogo and Popowsky (1) as modified by Lovenberg et al. (2). The sample is directly treated with a mixture of zinc acetate and sodium hydroxide, and then coupled with N,N′-dimethyl-p-phenylenediamine in the presence of ferric chloride to give methylene blue, which is then determined spectrophotometrically. The application of this method to the sulfide analysis of many iron-sulfur proteins has indicated that the amount of detectable labile sulfide is equivalent to the amount of iron present. However, lower results of labile sulfide content have been reported for some iron-sulfur proteins (3,4). Recently, Siegel et al. (5) reported that the total amount of released labile sulfide of NADPH-sulfide reductase depended upon the incubation time with the alkaline zinc reagent. We found that the original methylene blue method was also unsatisfactory for bovine adrenal ferredoxin and the reaction of the protein-bound sulfide with the alkaline zinc reagent was time1 dependent (6,7).In this communication is described an extension of the incubation with the alkaline zinc reagent in original methylene blue method which leads to a quantitative estimation of labile sulfide content in some iron-sulfur proteins.
1. Hydrogen sulphide inhaled, or sulphide or H 2 S injected in solution into the circulation, is carried for a time in the plasma in the form of an equilibrium mixture of sulphide and H 2 S. It only slowly penetrates into the red cells, where it is destroyed in reactions in which oxyhaemoglobin is reduced. The lethal dose of H 2 S will therefore vary according to the rate and site of its administration.
2. The physiological effects of hydrogen sulphide and other sulphides are similar to those of hydrocyanic acid, probably for the reason that both fix the iron in cytochrome A 3 , so reducing the oxygen intake of cells, and especially of nerve cells.
3. The most conspicuous actions of sulphides are on the nerve centres, which are first stimulated and then paralysed. The actions are reversible.
4. Because of the slow penetration of the red cells by H 2 S, or by the HS ion, the removal of sulphides from the plasma and their subsequent destruction is relatively slow, so that injections into the blood stream at sites from which the nerve centres are soon reached are more potent than those made at more remote places.
5. The reduction of oxyhaemoglobin resulting from the action of sulphides is reversible, and this is probably true also for the cytochrome A 3 . The action is therefore reversible, and the main treatment indicated is the application of artificial respiration.
A rapid and versatile method for the determination of sulphur in biological materials based on the stoicheiometric combination of mercury(II) and sulphur(II) with an acetone-dithizone indicator is described. Although slightly less sensitive than some other micro methods it has a wide range and is less subject to interference.
Heparinized rat blood containing sodium [35S]sulphide was perfused through isolated rat lungs, kidney or liver. The rate and extent of sulphide oxidation varied from one organ to another. In the isolated perfused lung system, [35S]sulphide was oxidized slowly to [35S]thiosulphate; only small amounts of [35S]sulphate were delectable, possibly due to the absence of sulphide oxidase. In the isolated perfused kidney system, [35S]sulphide was oxidized to [35S]sulphate with [35S]thiosulphate as a possible intermediate. In liver perfusion experiments [35S]sulphide was oxidized rapidly and almost exclusively to [35S]sulphate. The addition of unlabelled thiosulphate inhibited the formation of [35S]sulphate and caused the release of [35S]thiosulphate from the isolated liver. This suggests that thiosulphate is an intermediate in sulphide oxidation to sulphate. A mechanism for the rapid oxidation of sulphide to thiosulphate was shown to be present in rat liver mitochondria and, in the presence of glutathione, the thiosulphate was oxidized to sulphate. These results are discussed in relation to the contribution of lungs, kidney and liver to the oxidation of sulphide in vivo.
Post-mortem detection of sulfide in brain following H2S. Presented at the 11th Meeting of the International Association of Forensic Sciences
- L R Goodwin
- Mw Warenycia
- J Reiffenstein
- F P Dieken
- J D Taylor
L.R. Goodwin, MW. Warenycia, R,J. Reiffenstein, F.P. Dieken, and J.D. Taylor. Post-mortem detection of sulfide in brain following H2S. Presented at the 11th Meeting of the International Association of Forensic Sciences, Vancouver, B.C., 1987, paper TOXl-007.
An Introduction to Weather and Climate
- G T Trewartha
G.T. Trewartha. An Introduction to Weather and Climate. McGraw-Hill, New York, 1943. Manuscript received June 13, 1988; revision received August 23, 1988.