Recent advances in the application of gasotransmitters in spinal cord injury.

Spinal Cord Injury (SCI) is a condition characterized by complete or incomplete motor and sensory impairment, as well as dysfunction of the autonomic nervous system, caused by factors such as trauma, tumors, or inflammation. Current treatment methods primarily include traditional approaches like spinal canal decompression and internal fixation surgery, steroid pulse therapy, as well as newer techniques such as stem cell transplantation and brain-spinal cord interfaces. However, the above methods have limited efficacy in promoting axonal and neuronal regeneration. The challenge in medical research today lies in promoting spinal cord neuron regeneration and regulating the disrupted microenvironment of the spinal cord. Studies have shown that gas molecular therapy is increasingly used in medical research, with gasotransmitters such as hydrogen sulfide, nitric oxide, carbon monoxide, oxygen, and hydrogen exhibiting neuroprotective effects in central nervous system diseases. The gas molecular protect against neuronal death and reshape the microenvironment of spinal cord injuries by regulating oxidative, inflammatory and apoptotic processes. At present, gas therapy mainly relies on inhalation for systemic administration, which cannot effectively enrich and release gas in the spinal cord injury area, making it difficult to achieve the expected effects. With the rapid development of nanotechnology, the use of nanocarriers to achieve targeted enrichment and precise control release of gas at Sites of injury has become one of the emerging research directions in SCI. It has shown promising therapeutic effects in preclinical studies and is expected to bring new hope and opportunities for the treatment of SCI. In this review, we will briefly outline the therapeutic effects and research progress of gasotransmitters and nanogas in the treatment of SCI.

Targeting hydrogen sulfide and nitric oxide to repair cardiovascular injury after trauma.

The systemic cardiovascular effects of major trauma, especially neurotrauma, contribute to death and permanent disability in trauma patients and treatments are needed to improve outcomes. In some trauma patients, dysfunction of the autonomic nervous system produces a state of adrenergic overstimulation, causing either a sustained elevation in catecholamines (sympathetic storm) or oscillating bursts of paroxysmal sympathetic hyperactivity. Trauma can also activate innate immune responses that release cytokines and damage-associated molecular patterns into the circulation. This combination of altered autonomic nervous system function and widespread systemic inflammation produces secondary cardiovascular injury, including hypertension, damage to cardiac tissue, vascular endothelial dysfunction, coagulopathy and multiorgan failure. The gasotransmitters nitric oxide (NO) and hydrogen sulfide (H2S) are small gaseous molecules with potent effects on vascular tone regulation. Exogenous NO (inhaled) has potential therapeutic benefit in cardio-cerebrovascular diseases, but limited data suggests potential efficacy in traumatic brain injury (TBI). H2S is a modulator of NO signaling and autonomic nervous system function that has also been used as a drug for cardio-cerebrovascular diseases. The inhaled gases NO and H2S are potential treatments to restore cardio-cerebrovascular function in the post-trauma period.

Design, Synthesis and Evaluation of Novel Molecular Hybrids between Antiglaucoma Drugs and H2S Donors.

Glaucoma is a group of eye diseases consisting of optic nerve damage with corresponding loss of field vision and blindness. Hydrogen sulfide (H2S) is a gaseous neurotransmitter implicated in various pathophysiological processes. It is involved in the pathological mechanism of glaucomatous neuropathy and exerts promising effects in the treatment of this disease. In this work, we designed and synthetized new molecular hybrids between antiglaucoma drugs and H2S donors to combine the pharmacological effect of both moieties, providing a heightened therapy. Brinzolamide, betaxolol and brimonidine were linked to different H2S donors. The H2S-releasing properties of the new compounds were evaluated in a phosphate buffer solution by the amperometric approach, and evaluated in human primary corneal epithelial cells (HCEs) by spectrofluorometric measurements. Experimental data showed that compounds 1c, 1d and 3d were the hybrids with the best properties, characterized by a significant and long-lasting production of the gasotransmitter both in the aqueous solution (in the presence of L-cysteine) and in the intracellular environment. Because, to date, the donation of H2S by antiglaucoma H2S donor hybrids using non-immortalized corneal cells has never been reported, these results pave the way to further investigation of the potential efficacy of the newly synthesized compounds.

Gases in Sepsis: Novel Mediators and Therapeutic Targets.

Sepsis, a potentially lethal condition resulting from failure to control the initial infection, is associated with a dysregulated host defense response to pathogens and their toxins. Sepsis remains a leading cause of morbidity, mortality and disability worldwide. The pathophysiology of sepsis is very complicated and is not yet fully understood. Worse still, the development of effective therapeutic agents is still an unmet need and a great challenge. Gases, including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), are small-molecule biological mediators that are endogenously produced, mainly by enzyme-catalyzed reactions. Accumulating evidence suggests that these gaseous mediators are widely involved in the pathophysiology of sepsis. Many sepsis-associated alterations, such as the elimination of invasive pathogens, the resolution of disorganized inflammation and the preservation of the function of multiple organs and systems, are shaped by them. Increasing attention has been paid to developing therapeutic approaches targeting these molecules for sepsis/septic shock, taking advantage of the multiple actions played by NO, CO and H2S. Several preliminary studies have identified promising therapeutic strategies for gaseous-mediator-based treatments for sepsis. In this review article, we summarize the state-of-the-art knowledge on the pathophysiology of sepsis; the metabolism and physiological function of NO, CO and H2S; the crosstalk among these gaseous mediators; and their crucial effects on the development and progression of sepsis. In addition, we also briefly discuss the prospect of developing therapeutic interventions targeting these gaseous mediators for sepsis.

Hydrogen sulfide attenuates induction and prevents progress of the 6-hydroxydopamine-induced Parkinsonism in rat through activation of ATP-sensitive potassium channels and suppression of ER stress.

PURPOSE: Studies argue in favor of hydrogen sulfide (H2S) as the next potent therapeutic agent for neurodegenerative diseases. In present study, we investigated the effect of long term treatment with NaHS (as donor of H2S) on induction and progress of the 6-hydroxydopamine (6-OHDA) -induced Parkinsonism in rat. METHODS: The 6-OHDA was injected into medial forebrain bundle of right hemisphere by stereotaxic surgery. Behavioral tests and treatments were carried out to eight weeks after the toxin. Immunohistochemistry and western blotting were carried out to evaluate the survival of tyrosine hydroxylase (TH) -positive neurons in substantia nigra (SN) and also expression of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), the markers of endoplasmic reticulum (ER) stress, in striatum and SN. RESULTS: Eight weeks assessment of the behavioral symptoms showed that NaHS especially at dose of 100 µmol/kg attenuates remarkably induction of the Parkinsonism and prevents its progress. NaHS also increased the survival of TH- positive neurons and suppressed 6-OHDA- induced overexpression of GRP78 and CHOP. Blockade of ATP-sensitive potassium (K-ATP) channels with glibenclamide (Glib) prevented markedly the effect of NaHS on both the induction phase and survival of TH- positive neurons. But Glib did not affect the preventing effect of NaHS on the progress phase and its suppressing effect on the overexpression of ER stress markers. CONCLUSION: H2S attenuates induction of the 6-OHDA- induced Parkinsonism and also increases the survival of dopaminergic neurons through activation of K-ATP channels. H2S also prevents progress of the Parkinsonism probably through suppression of ER stress.

Role of Hydrogen Sulfide in Myocardial Ischemia-Reperfusion Injury.

ABSTRACT: Hydrogen sulfide (H2S), generally known as a new gas signal molecule after nitric oxide and carbon monoxide, has been found as an important endogenous gasotransmitter in the last few decades, and it plays a significant role in the cardiovascular system both pathologically and physiologically. In recent years, there is growing evidence that H2S provides myocardial protection against myocardial ischemia-reperfusion injury (MIRI), which resulted in an ongoing focus on the possible mechanisms of action accounting for the H2S cardioprotective effect. At present, lots of mechanisms of action have been verified through in vitro and in vivo models of I/R injury, such as S-sulfhydrated modification, antiapoptosis, effects on microRNA, bidirectional effect on autophagy, antioxidant stress, or interaction with NO and CO. With advances in understanding of the molecular pathogenesis of MIRI and pharmacology studies, the design, the development, and the pharmacological characterization of H2S donor drugs have made great important progress. This review summarizes the latest research progress on the role of H2S in MIRI, systematically explains the molecular mechanism of H2S affecting MIRI, and provides a new idea for the formulation of a myocardial protection strategy in the future.

Gasotransmitters for the Therapeutic Prevention of Hypertension and Kidney Disease.

Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), three major gasotransmitters, are involved in pleiotropic biofunctions. Research on their roles in hypertension and kidney disease has greatly expanded recently. The developing kidney can be programmed by various adverse in utero conditions by so-called renal programming, giving rise to hypertension and kidney disease in adulthood. Accordingly, early gasotransmitter-based interventions may have therapeutic potential to revoke programming processes, subsequently preventing hypertension and kidney disease of developmental origins. In this review, we describe the current knowledge of NO, CO, and H2S implicated in pregnancy, including in physiological and pathophysiological processes, highlighting their key roles in hypertension and kidney disease. We summarize current evidence of gasotransmitter-based interventions for prevention of hypertension and kidney disease in animal models. Continued study is required to assess the interplay among the gasotransmitters NO, CO, and H2S and renal programming, as well as a greater focus on further clinical translation.

Maternal disease and gasotransmitters.

The three known gasotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide are involved in key processes throughout pregnancy. Gasotransmitters are known to impact on smooth muscle tone, regulation of immune responses, and oxidative state of cells and their component molecules. Failure of the systems that tightly regulate gasotransmitter production and downstream effects are thought to contribute to common maternal diseases such as preeclampsia and preterm birth. Normal pregnancy-related changes in uterine blood flow depend heavily on gasotransmitter signaling. In preeclampsia, endothelial dysfunction is a major contributor to aberrant gasotransmitter signaling, resulting in hypertension after 20 weeks gestation. Maintenance of pregnancy to term also requires gasotransmitter-mediated uterine quiescence. As the appropriate signals for parturition occur, regulation of gasotransmitter signaling must work in concert with those endocrine signals in order for appropriate labor and delivery timing. Like preeclampsia, preterm birth may have origins in abnormal gasotransmitter signaling. We review the evidence for the involvement of gasotransmitters in preeclampsia and preterm birth, as well as mechanistic and molecular signaling targets.

Hydrogen Sulfide as Potential Regulatory Gasotransmitter in Arthritic Diseases.

The social and economic impact of chronic inflammatory diseases, such as arthritis, explains the growing interest of the research in this field. The antioxidant and anti-inflammatory properties of the endogenous gasotransmitter hydrogen sulfide (H2S) were recently demonstrated in the context of different inflammatory diseases. In particular, H2S is able to suppress the production of pro-inflammatory mediations by lymphocytes and innate immunity cells. Considering these biological effects of H2S, a potential role in the treatment of inflammatory arthritis, such as rheumatoid arthritis (RA), can be postulated. However, despite the growing interest in H2S, more evidence is needed to understand the pathophysiology and the potential of H2S as a therapeutic agent. Within this review, we provide an overview on H2S biological effects, on its role in immune-mediated inflammatory diseases, on H2S releasing drugs, and on systems of tissue repair and regeneration that are currently under investigation for potential therapeutic applications in arthritic diseases.

Atherosclerosis and the Hydrogen Sulfide Signaling Pathway - Therapeutic Approaches to Disease Prevention.

Hydrogen sulfide (H2S) is now admitted as a third gasotransmitter together with nitric oxide (NO) and carbon monoxide (CO), albeit it was originally considered as a foul and poisonous gas. Endogenous H2S production in mammalian cells is counting on the three enzymes acting on cysteine. Involvement of H2S in various physiological and pathological processes has been extensively studied in the last fifteen years. Mounting evidence suggests that H2S is able to protect against atherosclerosis development and progression. Exogenous H2S supplement has salutary effects on atherogenesis, and reduction of the endogenous H2S level accelerates atherosclerosis. The anti-atherosclerotic mechanisms of H2S have been descried in different aspects, including endothelium preservation, antioxidative action, anti-inflammatory responses, vasorelaxation, regulation of ion channels, etc. However, further investigation is still needed to help us gain more insights into the fundamental underlying mechanisms, and that will allow us to design better therapeutic applications of H2S in the treatment of atherosclerosis.

Hydrogen Sulfide Ameliorates Homocysteine-Induced Cognitive Dysfunction by Inhibition of Reactive Aldehydes Involving Upregulation of ALDH2.

Background: Homocysteine, a risk factor for Alzheimer's disease, induces cognitive dysfunction. Reactive aldehydes play an important role in cognitive dysfunction. Aldehyde-dehydrogenase 2 detoxifies reactive aldehydes. Hydrogen sulfide, a novel neuromodulator, has neuroprotective effects and regulates learning and memory. Our previous work confirmed that the disturbance of hydrogen sulfide synthesis is invovled in homocysteine-induced defects in learning and memory. Therefore, the present work was to explore whether hydrogen sulfide ameliorates homocysteine-generated cognitive dysfunction and to investigate whether its underlying mechanism is related to attenuating accumulation of reactive aldehydes by upregulation of aldehyde-dehydrogenase 2. Methods: The cognitive function of rats was assessed by the Morris water maze test and the novel object recognition test. The levels of malondialdehyde, 4-hydroxynonenal, and glutathione as well as the activity of aldehyde-dehydrogenase 2 were determined by enzyme linked immunosorbent assay; the expression of aldehyde-dehydrogenase 2 was detected by western blot. Results: The behavior experiments, Morris water maze test and novel objects recognition test, showed that homocysteine induced deficiency in learning and memory in rats, and this deficiency was reversed by treatment of NaHS (a donor of hydrogen sulfide). We demonstrated that NaHS inhibited homocysteine-induced increases in generations of MDA and 4-HNE in the hippocampus of rats and that hydrogen sulfide reversed homocysteine-induced decreases in the level of glutathione as well as the activity and expression of aldehyde-dehydrogenase 2 in the hippocampus of rats. Conclusion: Hydrogen sulfide ameliorates homocysteine-induced impairment in cognitive function by decreasing accumulation of reactive aldehydes as a result of upregulations of glutathione and aldehyde-dehydrogenase 2.

Hydrogen sulfide prevents renal ischemia-reperfusion injury in CLAWN miniature swine.

BACKGROUND: Hydrogen sulfide (H2S) has recently been reported to demonstrate both antiinflammatory and cytoprotective effects; however, its efficacy has not been well documented in large animal models. In this study, we examined whether the administration of H2S offers cytoprotective effects on renal ischemia-reperfusion injury (IRI) in a preclinical miniature swine model. METHODS: Major histocompatibility complex-inbred, CLAWN miniature swine (n = 9) underwent a right nephrectomy, followed by induction of a 120-min period of warm ischemia via placement of clamps on the left renal artery and vein. Group 1 (n = 3) underwent renal ischemia without H2S administration. Groups 2 (n = 3) and 3 (n = 3) received Na2S (prodrug of H2S) 10 min before reperfusion of the ischemic kidneys followed by a 30-min of Na2S postreperfusion intravenously (group 2) or selective administration of Na2S via the left renal artery (group 3). IRI was assessed by kidney biopsies, levels of inflammatory cytokines in sera and kidney tissue. RESULTS: Animals in group 1 had significantly higher serum creatinine levels compared with animals in groups 2 and 3 (P < 0.01). Histology showed severe tubular damage with TUNEL-positive cells in group 1 on postoperative day 2 compared with mild damage in group 2 and minimal damage in group 3. Furthermore, levels of inflammatory cytokines in both serum (interleukin-6 [IL-6], tumor necrosis factor-α, and high-mobility group box 1) and renal tissue (IL-1 and IL-6) in group 3 were markedly lower than in group 2, suggesting beneficial effects of selective Na2S administration. CONCLUSIONS: Na2S administration, especially via an organ selective approach, appears to potentially offer cytoprotective and antiinflammatory effects following renal IRI.

Hydrogen Sulfide Is an Antiviral and Antiinflammatory Endogenous Gasotransmitter in the Airways. Role in Respiratory Syncytial Virus Infection.

Hydrogen sulfide (H2S) is an endogenous gaseous transmitter whose role in the pathophysiology of several lung diseases has been increasingly appreciated. Our recent studies in vitro have shown, we believe for the first time, that H2S has an important antiviral and antiinflammatory activity in respiratory syncytial virus (RSV) infection, the leading cause of bronchiolitis and viral pneumonia in children. Our objective was to evaluate the therapeutic potential of GYY4137, a novel slow-releasing H2S donor, for the prevention and treatment of RSV-induced lung disease, as well as to investigate the role of endogenous H2S in a mouse model of RSV infection. Ten- to 12-week-old BALB/c mice treated with GYY4137, or C57BL/6J mice genetically deficient in the cystathionine γ-lyase enzyme, the major H2S-generating enzyme in the lung, were infected with RSV and assessed for viral replication, clinical disease, airway hyperresponsiveness, and inflammatory responses. Our results show that intranasal delivery of GYY4137 to RSV-infected mice significantly reduced viral replication and markedly improved clinical disease parameters and pulmonary dysfunction compared with the results in vehicle-treated control mice. The protective effect of the H2S donor was associated with a significant reduction of viral-induced proinflammatory mediators and lung cellular infiltrates. Furthermore, cystathionine γ-lyase-deficient mice showed significantly enhanced RSV-induced lung disease and viral replication compared with wild-type animals. Overall, our results indicate that H2S exerts a novel antiviral and antiinflammatory activity in the context of RSV infection and represent a potential novel pharmacological approach for ameliorating virus-induced lung disease.

Hydrogen Sulfide Promotes Learning and Memory and Suppresses Proinflammatory Cytokines in Repetitive Febrile Seizures.

OBJECTIVE: Hydrogen sulfide (H2S), as a novel gasotransmitter, plays important roles in a number of physiological and pathological processes. Its effectiveness has been demonstrated in different types of brain disorders but not in repetitive febrile seizure (febrile status epilepticus; FSE) models. This study aims to test whether a donor of H2S sodium sulfhydrate (NaHS) is also effective for FSE in rats. METHODS: FSE was induced in rat pups on postnatal day 10 in water at 45.0 ± 0.1°C for 10 consecutive days with or without preadministration of NaHS. Following evaluation of the latency and duration of hyperthermic seizures, impairment in learning and memory was measured by the Morris water maze test. Moreover, alterations of the microglial response and the production of proinflammatory cytokines IL-1ß and TNF-α were calculated in the hippocampus. RESULTS: We found that NaHS significantly increased the latency and decreased the duration of hyperthermic seizures. Furthermore, NaHS-treated pups showed less impairment in learning and memory. In addition, NaHS inhibited FSE-induced microglial responses and suppressed the production of IL-1ß and TNF-α in the hippocampus. CONCLUSION: NaHS appears to be effective for the treatment of FSE in infants and children, in part due to its anti-inflammatory action.

Hydrogen Sulfide Inhalation Improves Neurological Outcome via NF-κB-Mediated Inflammatory Pathway in a Rat Model of Cardiac Arrest and Resuscitation.

BACKGROUND/AIMS: The effects of H2S on cerebral inflammatory reaction after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) remain poorly understood. In this study, we investigated the effects of exogenous 40 ppm and 80 ppm H2S gas on inflammatory reaction and neurological outcome after CA/CPR. METHODS: CA was induced by ventricular fibrillation and followed by CPR. Forty or 80 ppm H2S was inhaled for 1 h immediately following CPR. The levels of IL-1ß, IL-6 and TNF-α, the myeloperoxidase (MPO) activity, the expression of iNOS and ICAM-1, and the phosphorylation and translocation of NF-κB were evaluated at 24 h after CA/ CPR. The tape removal test, survival rate and hippocampal neuronal counts were investigated at 14 d after CA/CPR. RESULTS: CA/CPR induced significant increases in IL-1ß, IL-6, TNF-α and MPO activity. The phosphorylation and translocation of NF-κB, and the expression of iNOS and ICAM-1 were increased significantly. Inhalation of 40 or 80 ppm H2S gas decreased these inflammatory cytokines. Furthermore, 40 or 80 ppm H2S inhibited the activation of NF-κB and the downstream proinflammatory mediators iNOS and ICAM-1. H2S inhalation also improved neurological function, 14-d survival rate, and reduced hippocampal neuronal loss. CONCLUSION: These results indicated that inhalation of H2S protected against brain injury after CA/CPR. The mechanisms underlying protective effects of H2S were associated with the inhibition of CA/ CPR-induced inflammation reactions by reducing IL-1ß, IL-6 and TNF-α, and concomitantly inhibiting the activation and infiltration of neutrophils. The beneficial effects of H2S might be mediated by downregulation of NF-κB and the downstream proinflammatory signaling pathway.

Effects of Hydrogen Sulfide on Modulation of Theta-Gamma Coupling in Hippocampus in Vascular Dementia Rats.

Our previous study showed that hydrogen sulfide (H2S) could alleviate the cognitive deficits in vascular dementia (VD) rats associated with the improvement of synaptic plasticity. Neural oscillations are reported to interact with each other through either identical-frequency or cross-frequency coupling. This study examined whether impaired neural couplings could be alleviated by H2S in the hippocampal CA3-CA1 of VD rats and explored its possible mechanism. A VD rat model was established by two-vessel occlusion. Sodium hydrosulfide (NaHS), a kind of H2S donor, was administered intraperitoneally (5.6 mg/kg/day) for 3 weeks. Local field potentials were simultaneously collected in the hippocampal CA3 and CA1. The effects of NaHS on the modulation of theta-gamma coupling were evaluated by using the measurements of both phase-phase coupling and phase-amplitude coupling, while several other approaches including behavior, electrophysiology, western blot, immunofluorescence staining were also employed. The results showed that NaHS significantly prevented spatial learning and memory impairments (p < 0.01). NaHS considerably alleviated the impairment of neural coupling in VD rats in an identical-frequency rhythm and between cross-frequency bands. Moreover, the expression of cystathionine-ß-synthase (CBS) was markedly attenuated in VD rats. NaHS elevated the expression of CBS to maintain the intrinsic balance of H2S. Interestingly, it was observed that NaHS increased the protein expression of N-methyl-D-aspartic acid receptor 2A (NMDAR2A) in VD rats. In conclusion, the data suggest that NaHS played the neuroprotective role partly via modulating the expression of NMDAR2A in order to alleviate the impairments of neural couplings in VD rats.

The therapeutic potential of carbon monoxide for inflammatory bowel disease.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, are chronic, relapsing and remitting inflammatory disorders of the intestinal tract. Because the precise pathogenesis of IBD remains unclear, it is important to investigate the pathogenesis of IBD and to evaluate new anti-inflammatory strategies. Recent accumulating evidence has suggested that carbon monoxide (CO) may act as an endogenous defensive gaseous molecule to reduce inflammation and tissue injury in various organ injury models, including intestinal inflammation. Furthermore, exogenous CO administration at low concentrations is protective against intestinal inflammation. These data suggest that CO may be a novel therapeutic molecule in patients with IBD. In this review, we present what is currently known regarding the therapeutic potential of CO in intestinal inflammation.

Discoveries of hydrogen sulfide as a novel cardiovascular therapeutic.

Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule that elicits a number of cytoprotective effects in mammalian species. H2S was originally considered toxic at elevated levels, but 15 years ago the labile molecule was discovered in mammalian tissue and termed a gasotransmitter, thus opening the door for research aimed towards understanding its physiologic nature. Since then, novel findings have depicted the beneficial aspects of H2S therapy, such as vasodilation, antioxidant upregulation, inflammation inhibition, and activation of anti-apoptotic pathways. These cytoprotective alterations effectively treat multiple forms of cardiac injury at the preclinical level of research. The field has progressed towards instituting novel H2S donors that prove more effective at activating the subsequent cardioprotective enhancements over longer time periods. As more findings explore the efficacy of H2S, research focused on detection of sulfhydrated targets is on the rise. Understanding the molecular mechanisms that stem from H2S treatment may lead the field towards powerful therapeutics in the clinical setting. This review will discuss the cytoprotective and cardioprotective effects of H2S therapy, provide analysis on the molecular alterations that lead to these enhancements, and explore recently developed therapeutics that may bring this gasotransmitter into the clinic in the near future.

Protective effect of hydrogen sulfide on hyperbaric hyperoxia-induced lung injury in a rat model.

Hyperbaric oxygen therapy is one of the most widely used clinical interventions to counteract insufficient pulmonary oxygen delivery in patients with severe lung injury. However, prolonged exposure to hyperoxia leads to inflammation and acute lung injury. This study aimed to investigate the protective effect of hydrogen sulfide on hyperbaric hyperoxia-induced lung injury. Rats were intraperitoneally treated with sodium hydrosulphide (NaHS) at 28 µmol/kg immediately before hyperoxia exposure and then exposed to pure oxygen at 2.5 atmospheres absolute (atm abs) with continuous ventilation for six hours, Immediately after hyperoxia exposure, rats were sacrificed via anesthesia. The bronchoalveolar lavage fluid (BALF) was harvested for the detection of protein concentration and IL-1 content, and the lungs were collected for HE staining, TUNEL staining and detection of wet/dry weight ratio. Our results showed hyperbaric hyperoixa exposure could significantly damage the lung (HE staining), increase the protein and IL-13 in the BALF, elevate the wet/dry Weight ratio and raise the TUNEL positive cells. However, pre-treatment with hydrogen sulfide improved the lung morphology, reduced the TUNEL positive cells and attenuated the lung inflammation (reduction in IL-13 of BALF and HE staining). Taken together, our findings indicate that hydrogen sulfide pretreatment may exert protective effects on hyperbaric hyperoxia-induced lung injury.

Hydrogels for Gasotransmitter Delivery: Nitric Oxide, Carbon Monoxide, and Hydrogen Sulfide.

Gasotransmitters, gaseous signaling molecules including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2 S), maintain myriad physiological processes. Low levels of gasotransmitters are often associated with specific problems or diseases, so NO, CO, and H2 S hold potential in treating bacterial infections, chronic wounds, myocardial infarction, ischemia, and various other diseases. However, their clinical applications as therapeutic agents are limited due to their gaseous nature, short half-life, and broad physiological roles. One route toward the greater application of gasotransmitters in medicine is through localized delivery. Hydrogels are attractive biomedical materials for the controlled release of embedded therapeutics as they are typically biocompatible, possess high water content, have tunable mechanical properties, and are injectable in certain cases. Hydrogel-based gasotransmitter delivery systems began with NO, and hydrogels for CO and H2 S have appeared more recently. In this review, the biological importance of gasotransmitters is highlighted, and the fabrication of hydrogel materials is discussed, distinguishing between methods used to physically encapsulate small molecule gasotransmitter donor compounds or chemically tether them to a hydrogel scaffold. The release behavior and potential therapeutic applications of gasotransmitter-releasing hydrogels are also detailed. Finally, the authors envision the future of this field and describe challenges moving forward.