H2S Inhalation Research Articles

Chronic inhalation of H2S in low concentration induces immunotoxicity and inflammatory effects in lung tissue of rats

Hydrogen sulfide (H2S) is a typical odour compound mainly causing respiratory and central nervous system symptoms. However, the immunotoxicity of inhaled H2S and the underlying mechanisms remain largely unknown. In this study, a low-dose inhalation exposure to H2S was arranged to observe inflammatory response and immunotoxicity in lung tissue of rats. Low concentrations of H2S exposure affected the immune level of pulmonary tissue and peripheral blood. Significant pathological changes in lung tissue in the exposure group were observed. At low concentration, H2S not only induced the upregulation of AQP-4 and MMP-9 expression but also stimulated immune responses, initiating various anti-inflammatory and inflammatory factors, altering tissue homeostatic environments. The TNF and chemokine signaling pathway played an important role which can promote the deterioration of pulmonary inflammatory processes and lead to lung injury and fibrosis. Excessive immune response causes an inflammatory effect and blood-gas barrier damage. These data will be of value in evaluating future occupational health risks and providing technical support for the further development of reliable, sensitive, and easy-to-use screening indicators of exposure injury.

A dynamic approach to identify hazardous areas for H2S-containing natural gas release and explosion accidents on offshore platforms

Many efforts have been made to predict and mitigate the toxic impact and explosion impact. However, they are inadequate for the chain accident of toxic gas-containing flammable gas release and explosion since these two hazardous impacts can happen continuously. Accordingly, an integrated approach concerning chain accident consequence assessment is proposed, in which the human behavior is taken into account. The risk-based concept and grid-based concept are introduced in this approach to integrate the adverse impacts. The approach is applied to a hypothetical chain accident involving H2S-containing natural gas release and explosion on an offshore platform. The emergency evacuation is considered by establishing an emergency evacuation time model. A cumulative H2S inhalation dose along each evacuation trajectory is derived to evaluate the toxic impact by considering the temporal-spatial variation of both H2S profile and sufferers’ positions. The maximum explosion overpressures in the real-time position of the sufferers are extracted to predict the explosion impact. The proposed approach is systematic and efficient for practical engineering applications. It can help to develop safety measures and improve the contingency plan.

Mechanism determination on the interactive effects between host immunity and gut microbiome to resist consecutive hydrogen sulfide inhalation of laying hens

The study aims to investigate the underlying mechanism of the interactions between intestinal microbiota and host immunity-related parameters in response to H2S inhalation of layer hens. A total of 180 healthy 300-day-old Lohmann pink hens with similar body weight were randomly allotted into the control (CON) and the hydrogen sulfide (H2S) treatments for an 8-wk-long feeding procedure. Productive performances, antioxidant capacities, immunity-related parameters, blood metabolites, and cecal microbiota were measured to determine the physiological and gastrointestinal responses to H2S treatment. Results showed that feed intake, egg production, eggshell strength, Haugh unit, and relative yolk weight significantly declined under H2S treatment compared with CON (P < 0.05). Antioxidant and immunity-related parameters showed that glutathione peroxidase, IL-4, and TNF-α contents significantly decreased, whereas contents of IL-1β, IL-2, and IL-6 significantly increased after H2S treatment (P < 0.05). Further metabolic results showed H2S treatment upregulated 2-mercaptobenzothiazole, D-glucopyranuronic acid, deoxyuridine, cholic acid, and mimosine, etc., which mainly enriched into the pyrimidine metabolism, beta-alanine metabolism, valine, leucine, and isoleucine biosynthesis, and pantothenate and CoA biosynthesis pathways. Meanwhile, aceturic acid, 9-oxodecenoic acid, palmitoleic acid, lauric acid, linoleic acid, oleic acid, and valeric acid mainly contributed to the downregulated metabolites, and enriched into the biosynthesis of unsaturated fatty acids, amino sugar and nucleotide sugar metabolism, tryptophan metabolism and linoleic metabolism. Moreover, H2S treatment significantly proliferated the relative abundances of Faecalibacterium, Ruminococcaceae, and Streptococcus, while decreased Prevotella, Lactobacillus, Bifidobacterium, Clostridium, and Campylobacter (P < 0.05). The altered bacteria were functionally enriched in the carbohydrate metabolism, amino acid metabolism, and metabolism of cofactors and vitamins pathways. H2S treatment also significantly downregulated the expression of ZO-1, Claudin 4, and Claudin 7 (P < 0.05). In summary, intestinal microbial communities altered significantly to make proper adaptations in interacting with the host immune systems through the immunity-related metabolites secretion, and epithelial tight-junction-related genes expressions, purposely to regulate the productive performance under hydrogen sulfide inhalation.

H2S Alleviates Propofol-Induced Impaired Learning and Memory by Promoting Nuclear Translocation of Nrf2 and Inhibiting Apoptosis and Pyroptosis in Hippocampal Neurons.

Repeated exposure to propofol can affect their learning and memory functions, but the mechanism remains unclear. The current study aimed to investigate the mechanism underlying the effect of hydrogen sulfide (H2S) on the alleviation of propofol-induced learning and memory impairment, mediated by promoting nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibiting apoptosis and pyroptosis in hippocampal neurons. Rats used in this study were successively exposed to 200 mg/kg propofol for 8 consecutive weeks, followed by inhalation of 10, 40 or 80 ppm H2S. Subsequently, the effects of different concentrations of H2S on learning and memory were assessed using the water maze assay. Additionally, the effects of H2S on cell apoptosis and pyroptosis and nuclear translocation of Nrf2 in hippocampal neurons were also determined. Furthermore, NaHS (200 μmol/L) was used as an in vitro donor for H2S, and rescue experiments were carried out following Nrf2 knockdown in H19-7 cells. Moreover, Nrf2 function was inhibited following treatment with an intraperitoneal injection of ML385 (30 mg/kg) in the rats. The effects of H2S on reactive oxygen species (ROS) generation, cell apoptosis, and pyroptosis in propofol-treated and Nrf2-deficient H19-7 cells were also investigated. Exposure to propofol for 8 weeks affected the ability of the rats to find underwater platforms (p < 0.01). Further, the exposure induced cell apoptosis and NLR family pyrin domain containing 3 (NLRP3)-related pyroptosis (p < 0.01). Although inhalation of 10 ppm H2S did not attenuate the aforementioned effects (p > 0.05), exposure to 40 and 80 ppm H2S significantly alleviated propofol-induced injury in the hippocampal neurons (p < 0.01). However, the protective effect of 80 ppm H2S was more obvious as compared to that of the other two doses (p < 0.01). In addition, Nrf2 knockdown aggravated the propofol-induced cell pyroptosis and apoptosis as well as reversed the protective effect of H2S against these processes (p < 0.01). In vivo experiments in this study demonstrated that Nrf2 inhibition abrogated the protective effects of H2S inhalation against learning and memory impairment as well as propofol-induced cell apoptosis and pyroptosis in rats (p < 0.01). H2S could attenuate propofol-induced damage in hippocampal neurons by promoting the nuclear translocation of Nrf2 and inhibiting cell apoptosis and pyroptosis.

Therapeutic applications of hydrogen sulfide and novel donors for cerebral ischemic stroke: a narrative review.

Ischemic stroke happens when the blood supply to the brain is obstructed and it is associated with numerous complex mechanisms, such as activated apoptosis genes, oxidative stress and reaction of inflammation, which finally result in neurological deficits. Several gases have been proved to have neuroprotective roles, even the classic gases that are thought to be toxic such as hydrogen sulfide (H2S). H2S is the third identified endogenous gas signaling molecule following carbon monoxide and nitric oxide. H2S plays a significant role in stroke. Inhalation of H2S can attenuate cerebral infarct volume and promote neurological function in a rat model of middle cerebral artery occlusion to reduce ischemic stroke-induced injury in vivo and in vitro as a result. Therefore, H2S can be clinically used to reduce ischemic stroke-induced injury. This review introduces the toxic mechanisms and effects of H2S on cerebral ischemic stroke

Inhalative as well as Intravenous Administration of H2S Provides Neuroprotection after Ischemia and Reperfusion Injury in the Rats' Retina.

Background: Neuronal ischemia-reperfusion injury (IRI), such as it can occur in glaucoma or strokes, is associated with neuronal cell death and irreversible loss of function of the affected tissue. Hydrogen sulfide (H2S) is considered a potentially neuroprotective substance, but the most effective route of application and the underlying mechanism remain to be determined. Methods: Ischemia-reperfusion injury was induced in rats by a temporary increase in intraocular pressure (1 h). H2S was then applied by inhalation (80 ppm at 0, 1.5, and 3 h after reperfusion) or by intravenous administration of the slow-releasing H2S donor GYY 4137. After 24 h, the retinas were harvested for Western blotting, qPCR, and immunohistochemical staining. Retinal ganglion cell survival was evaluated 7 days after ischemia. Results: Both inhalative and intravenously delivered H2S reduced retinal ganglion cell death with a better result from inhalative application. H2S inhalation for 1.5 h, as well as GYY 4137 treatment, increased p38 phosphorylation. Both forms of application enhanced the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and inhalation showed a significant increase at all three time points. H2S treatment also reduced apoptotic and inflammatory markers, such as caspase-3, intracellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase (iNOS). The protective effect of H2S was partly abolished by the ERK1/2 inhibitor PD98059. Inhalative H2S also reduced the heat shock response including heme oxygenase (HO-1) and heat shock protein 70 (HSP-70) and the expression of radical scavengers such as superoxide dismutases (SOD1, SOD2) and catalase. Conclusion: Hydrogen sulfide acts, at least in part, via the mitogen-activated protein kinase (MAPK) ERK1/2 to reduce apoptosis and inflammation. Both inhalative H2S and intravenous GYY 4137 administrations can improve neuronal cell survival.

H2S in Critical Illness-A New Horizon for Sodium Thiosulfate?

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.

Liver Transplantation After Organ Donation Due to Hydrogen Sulfide Intoxication: Report of the First Case.

The discrepancy of patients on the waiting list and the availability of organs suitable for transplantation continues to represent a relevant problem in transplantation medicine. Regarding liver transplantation, the increasing use of organs from donors with so-called extended criteria meanwhile has become daily practice in many countries.1 Consequently, every potential donor reported is carefully evaluated for suitability for organ donation. When a liver from a young brain-dead donor after hydrogen sulfide (H2S) intoxication was offered for a high-urgency listed patient, research of the literature did not provide any help for decision making in organ allocation. Herewith, we want to share our experience following the successful use of this donor liver for transplantation. A 60-y-old female patient with acute liver failure caused by an autoimmune hepatitis was transferred to our center and eventually listed for high-urgency liver transplantation following biopsy-proven diagnosis and rapid worsening of the clinical condition despite thorough intensive medical treatment (see Figure 1). Within 5 h after approval of high-urgency status, we were offered a liver from a 19-y-old female brain-dead donor following H2S intoxication in suicidal intent. Apart from depression, the donor was in excellent general condition before intoxication and had no other known illnesses. Despite recently promoted organ protective effects in experimental studies,2 inhalation of H2S in higher concentrations is highly toxic and eventually led to cardiac arrest in this patient.3 Following a short period of resuscitation, the donor was admitted to an intensive care unit and eventually diagnosed brain dead. Within 24 h, severe lung edema and subsequently respiratory failure developed as signs of multiorgan failure. Regarding the liver, apart from an initial peak of transaminases (peak AST and ALT levels of 357 and 438 U/L, respectively), the laboratory findings were all unremarkable. Because of the severe condition of our recipient with severe hepatic encephalopathy, we thus accepted the organ after intense interdisciplinary discussion despite the lack of any data on successful use of organs for transplant under these conditions. Upon arrival of the organ at our center, histological work-up of the liver by frozen section was performed despite excellent macroscopic appearance, which did not reveal any signs of acute liver injury or chronic alterations‚ such as steatosis or fibrosis (see Figure 2). Subsequent liver transplantation was completely uneventful. The patient’s clinical condition improved rapidly, with discharge at day 15 after transplantation (see Figure 1). During follow-up of 6 mo, no irregularities were observed, with excellent graft function and medical condition of the recipient at last visit. In conclusion, to our knowledge‚ this is the first report of a liver transplant from a brain-dead donor after hydrogen sulfide intoxication. Based on this single-case experience, potential donors after hydrogen sulfide intoxication should be carefully evaluated and considered for organ donation. Particularly evaluation of potential grafts applying normothermic machine perfusion might represent another valuable option in case of less urgent conditions of the recipients.4FIGURE 1.: Course of laboratory parameters (AST, ALT [both U/L], bilirubin [µmol/L], and INR) of the recipient before and after LTx, with time points of liver biopsy, PE and steroid therapy‚ and day of transplantation indicated by gray bars. ALT, alanine aminotransferase; AST, aspartate aminotransferase; INR, international normalized ratio; LTx, liver transplantation; PE, plasmapheresis.FIGURE 2.: Histopathology of liver wedge biopsy: hematoxylin and eosin staining shows no steatosis, fibrosis, or cirrhosis ([A] ×40 magnification and [B] ×100 magnification), and Elastica van Gieson staining highlights absence of fibrosis within the liver parenchyma ([C] ×40 magnification and [D] ×100 magnification).

A Sulfonyl Azide-Based Sulfide Scavenger Rescues Mice from Lethal Hydrogen Sulfide Intoxication.

Exposure to hydrogen sulfide (H2S) can cause neurotoxicity and cardiopulmonary arrest. Resuscitating victims of sulfide intoxication is extremely difficult, and survivors often exhibit persistent neurological deficits. However, no specific antidote is available for sulfide intoxication. The objective of this study was to examine whether administration of a sulfonyl azide-based sulfide-specific scavenger, SS20, would rescue mice in models of H2S intoxication: ongoing exposure and post-cardiopulmonary arrest. In the ongoing exposure model, SS20 (1250 µmol/kg) or vehicle was administered to awake CD-1 mice intraperitoneally at 10 min after breathing 790 ppm of H2S followed by another 30 min of H2S inhalation. Effects of SS20 on survival were assessed. In the post-cardiopulmonary arrest model, cardiopulmonary arrest was induced by an intraperitoneal administration of sodium sulfide nonahydrate (125 mg/kg) in anesthetized mice. After 1 min of cardiopulmonary arrest, mice were resuscitated with intravenous administration of SS20 (250 µmol/kg) or vehicle. Effects of SS20 on survival, neurological outcomes, and plasma H2S levels were evaluated. Administration of SS20 during ongoing H2S inhalation improved 24-h survival (6/6 [100%] in SS20 vs 1/6 [17%] in vehicle; p = .0043). Post-arrest administration of SS20 improved 7-day survival (4/10 [40%] in SS20 vs 0/10 [0%] in vehicle; p = .0038) and neurological outcomes after resuscitation. SS20 decreased plasma H2S levels to pre-arrest baseline immediately after reperfusion and shortened the time to return of spontaneous circulation and respiration. These results suggest that SS20 is an effective antidote against lethal H2S intoxication, even when administered after cardiopulmonary arrest.

Assessment of H2S and BTEX concentrations in ambient air using passive sampling method and the health risks.

Wastewater treatment plants (WWTPs) may be a source of nuisance in neighbouring places due to hydrogen sulphide (H2S) and BTEX (benzene, toluene, ethylbenzene, and xylenes) emissions. In this study, samples were collected from WWTP workplace ambient air and outdoor ambient air around one of the largest WWTPs in Istanbul with a capacity of 250,000 m3/day to evaluate the effects of H2S and BTEX emissions. Samples were collected in three seasons for 15-day durations: winter (November 2015), spring (May 2015), and summer (August 2016). Average concentrations of H2S and BTEX were determined as 1.1 and 56.2µg/m3, respectively. Average concentrations BTEX components were 4.9, 20.7, 6.4, and 24.2µg/m3, respectively. Health risk assessment for plant workers and local residents was performed for H2S and BTEX inhalation exposure using the method by USEPA. Results show that H2S and BTEX emissions do not have harmful effects on human health.

H2S as a Therapeutic Adjuvant Against COVID-19: Why and How?

H2S as a Therapeutic Adjuvant Against COVID-19: Why and How?

INTRATRACHEAL SALINE BOLUS INCREASES SURVIVABILITY IN RABBITS EXPOSED TO LETHAL DOSE OF INHALED HYDROGEN SULFIDE

SESSION TITLE: Pharmacotherapeutics Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Hydrogen Sulfide (H2S) is a highly toxic, flammable, and colorless gas. In addition to industrial accident risks, H2S has been identified as a potential terrorist chemical and military threat agent for use in mass-casualty events, with no effective antidotes. In this study, we investigate the effects of a small volume of intratracheal (IT) slow-drip saline versus IT fast bolus saline treatment to prolong survival in H2S exposure in an animal model for potential treatments during mass-casualty crises. METHODS: The effects of IT saline in H2S exposure were tested on 49 New Zealand white male rabbits. Animals were anesthetized and intubated, but not ventilated. H2S gas (2000 ppm) was delivered along with a 1.5% isoflurane in air mixture (2.25 liters/min)for 30 minutes.Three groups were compared: no saline into endotracheal tube control(n=16), IT slow saline drip (n=17) and fast IT saline bolus group (n=16). Animals in IT slow drip saline group received 3cc of saline in 3 minutes, while fast saline bolus group animals received it in less than 20 seconds. Both treatment groups were compared to the control group. Systemic blood pressure and heart rate were continuously monitored.The changes in tissue oxy and deoxy hemoglobin concentrations were measured non-invasively over the brain region using continuous wave near infrared spectroscopy. Animals were deemed survivors at 60 minutes from the start of toxic exposure. Animals were sacrificed when systolic blood pressure dropped below 20 mmHg. RESULTS: The average weight for all animals(n=49) in this study was 3.88 ± 0.35 kg, mean ± SD. The survival rate of the fast saline, slow saline, and the control groups were 56.25%, and,23.53%, and 25%.Log-rank (Mantel-Cox) test showed that the survivability in the treatment groups and control groups are significantly different (p=0.0417). Slow saline group versus fast saline group difference was also significant (p=0.0140). The slow saline group compared to control group results were not different (p=0.7031). CONCLUSIONS: The rapid administration of a small volume of saline bolus given via IT route was effective in prolonging survival in lethal H2S exposure when given rapidly. These findings appear likely due to the rapid bolus stimulating cough and breathing responses in apneic animals, in contrast to the slow dripping of a similar amount of saline.While the stimulation of breathing leads to inhalation of more H2S in this model, improvement in hypoxemia in these animals appears to be of greater importance than the risk of additional H2S exposure.Thus, we propose that the hypoxemia from H2S-induced respiratory depression is a major contributor to mortality compared to the metabolic inhibition of cytochromes from H2S in this scenario. CLINICAL IMPLICATIONS: This has potential implications for the treatment victims of H2S exposure who cannot be removed from the exposure site as this commonly occurs in mass-casualty events. DISCLOSURES: No relevant relationships by vikhyat bebarta, source=Web Response No relevant relationships by Gerry Boss, source=Web Response No relevant relationships by Matthew Brenner, source=Web Response No relevant relationships by Tanya Burney, source=Web Response No relevant relationships by Adriano Chan, source=Web Response No relevant relationships by Melina Doosty, source=Web Response No relevant relationships by Philippe Haouzi, source=Web Response No relevant relationships by Tara Hendry-Hofer, source=Web Response No relevant relationships by Jangwoen Lee, source=Web Response No relevant relationships by Sari Mahon, source=Web Response No relevant relationships by David Mukai, source=Web Response No relevant relationships by George Philipopoulos, source=Web Response

Air emissions and health risk assessment around abattoir facility

The study assessed the impacts of abattoir activities on ambient air quality and health risk associated with exposure to PM2.5 and PM10, H2S, SO2 and NH3. Air samplings were done simultaneously around the abattoir at three points for sixty consecutive days (October to November) and standard methods adopted for the samplings and analysis. Health risks associated with exposure to PM10 and PM2.5 were estimated, using attributable fractions, relative risk and the excess lifetime cancer risk. The non-carcinogenic risks induced by the inhalation of H2S, SO2 and NH3 were also evaluated using hazard quotient (HQ). The results indicated that the average concentrations of 18.75 μg/m3, 89.17 μg/m3 and 0.1ppm for PM2.5, PM10 and NO2 respectively, were higher than the World Health Organization (WHO), National Ambient Air Quality Standard (NAAQS) and Federal Ministry of Environment (FMEnv) permissible limits. Air Quality Index showed that the ambient air quality in respect of CO and NH3 was very good, moderate for PM10 and was very poor for NO2 and SO2. It was also shown that 0.32% of deaths from lung cancer, and 0.23% from cardiopulmonary could be avoided if PM2.5 is reduced to 3 μg/m3 and while about 0.14% of all-cause mortality could be avoided if PM10 is reduced to 10 μg/m3. In similar manner, at least 0.45% likelihood that an individual in a group of people exposed to PM2.5 100m away from the burning point may have health issue (lung cancer) than an individual from another set of people that is exposed to baseline concentration of 3 μg/m3. All the HQ values exceeded the threshold value, set at the unity, implying that H2S, SO2 and NH3 are likely to cause adverse health effects in the area. Conclusively, continuous operation of this abattoir within the residential area can constitute a great environmental menace to the residents of the area and can result in complication to those with existing health challenge.

Hydrogen sulfide attenuates diabetic neuropathic pain through NO/cGMP/PKG pathway and μ-opioid receptor.

There are currently approximately 425 million diabetic patients worldwide, of which approximately 90% of patients with diabetes suffer from neuropathy. Diabetic neuropathic pain (DNP) is a common complication of diabetic neuropathy. Nearly half of the patients hospitalized with diabetes have pain symptoms or symptoms related to neurological injury, and the incidence increases with age and diabetic duration. Anti-DNP analgesics have either limited therapeutic effects or serious side effects or lack of clinical trials, which has limited their application. Physiopathological mechanisms and treatment of DNP remain a significant challenge. The present confirmed that inhalation of H2S may attenuate the diabetic neuropathic pain through NO/cGMP/PKG pathway and μ-opioid receptor. It provides us the animal study foundation for the application of H2S on the treatment of DNP and clarifies some target molecules in the pain modulation of DNP.

Air Quality and Human Health Risk Assessment in the Residential Areas at the Proximity of the Nkolfoulou Landfill in Yaoundé Metropolis, Cameroon

Landfill operations generate particulate matters (PM) and toxic gases that can jeopardize human health. This study was conducted in February 2016 to assess the air quality in the residential areas around the Nkolfoulou landfill in Yaoundé. The concentrations of PM2.5 and PM10 were determined with Dust Sentry while those of CO, O3, NO2, CH4, CO2, CH2O, H2S, and SO2 were measured using gas sensors. At the landfill neighborhood, 30% of the daily mean concentrations of PM2.5 and PM10 crossed the daily safe limits. The concentrations of CO, O3, NO2, SO2, and H2S recorded at the propinquity of the landfill complied with the emission standards. Near the landfill, hourly mean concentrations of CH2O and H2S higher than their odour thresholds were recorded at each sampling site. The concentrations of CH4 were less than its lower explosive limit while those of CO2 were far below the safe limit for occupational health. The values of cancer risk (CR) due to the inhalation of CH2O were &gt;10−6 while those of hazard index (HI) due to the inhalation of CH2O, H2S, and SO2 were &lt;1. Thus, there might be increased cancer risks at the Nkolfoulou landfill neighborhood, whereas the increased non-cancer risks were low. 96.76% of the daily average levels of air pollutants registered near the landfill surpassed those recorded at the remote control site. Hence, the landfill operations might be supplying air pollutants to the neighbouring residential areas.

Hydrogen sulfide exposure triggers chicken trachea inflammatory injury through oxidative stress-mediated FOS/IL8 signaling.

Hydrogen sulfide (H2S) is well known to cause irritation and damage to airway following inhalation, but the mechanism by which H2S contributes to airway toxicity is unclear. In order to assess the respiratory toxicity of H2S inhalation in chicken trachea, we investigated the change of oxidative stress parameters, tracheal tissue structure and transcriptome profiles of chicken trachea exposed to H2S for 42 days. The results showed H2S exposure induced oxidative stress and inflammation in trachea. The ultrastructural analysis revealed loss of cilia and accumulation of mucus in tracheal epithelium. Differentially expressed genes (DEGs) analysis indicated 454 genes were significantly changed, including 136 genes upregulated and 318 genes downregulated. Gene ontology and KEGG analysis showed many genes involved in response to oxidative stress, inflammatory and immune response, which might contribute to H2S-induced tracheal inflammatory injury. Among those genes, N-acetyl-L-cysteine (NAC) treatment blocked the H2S-triggered expression of FOS and IL8. Silencing FOS by siRNA inhibited H2S-induced expression of IL8. Taken together, we concluded that H2S induced oxidative stress leads to tracheal inflammation through FOS/IL8 signaling, leading to excessive mucus secretion and absence of cilia. These results provide new insights for unveiling the biological effects of H2S in vivo and in vitro.

DEVELOPMENT OF AN INHALATION MODEL FOR STUDYING HYDROGEN SULFIDE EXPOSURES

SESSION TITLE: Obstructive Lung Disease/Toxic Inhalation SESSION TYPE: Original Investigations PRESENTED ON: 10/07/2018 02:15 PM - 03:15 PM PURPOSE: Hydrogen sulfide (H2S) is a toxic and potent gas, and human exposures occur frequently in nature and many industries; moreover, hydrogen sulfide inhalation can be used as a weapon of mass destruction and can be a major chemical threat to military personnel. H2S has been reported to cause direct pulmonary toxicity when inhaled. There is no current effective antidote for H2S, and understanding the underlying pathophysiology is a first step to identifying a potential antidote. Antidotes that can be given rapidly in a small volume and at a delayed time after sulfide exposure are a priority. To come up with an effective treatment, having a carefully controlled model, which can simulate a realistic scenario of toxic inhalation exposure as would likely be experienced by victims is essential. METHODS: A custom gas inhalation circuit was designed to deliver isoflurane anesthesia and hydrogen sulfide in a compressed air flow-by mixture to intubated New Zealand White rabbits. Compressed air was supplied to an Ohmeda VMC anesthesia machine, which vaporized isoflurane. The H2S gas was produced by dripping a 320mM NaHS solution at a rate of 2.5ml/min into a reaction vessel containing 150 ml 3N HCl. The H2S, air and isoflurane mixture then exited the reaction vessel and was delivered to the animal subject for inhalation thru a disposable respiratory non-rebreathing valve. The respiratory circuit, reaction vessel and animal subject were located within a fume hood, and the exhaled gas was sent to an activated charcoal filter (f/air) where the isoflurane and H2S were absorbed. H2S gas levels were monitored within the hood and circuit during the experiments. The in situ generation system enables high dose exposures without requiring a large tank of dangerous lethal gas present.Rabbit vital signs and physiological measures, including SPO2, heart rate, blood pressure, and minute ventilation were monitored and recorded throughout the experiment. Fatal exposure was defined as apnea accompanied by a decrease in blood pressure to a systolic value less than 20mmHg, at which point animals were euthanized. RESULTS: Rabbits experienced the first apnea episode within 5 minutes of H2S exposure. Heart rate initially decreased, and was accompanied by a decrease in blood pressure from a baseline mean arterial pressure of 52mmHg to less than 20mmHg systolic. The total volume of inhaled gas in this control group (n=6) averaged 7.35L. Average survival time was 10.5 minutes CONCLUSIONS: Death from H2S exposure occurs within minutes. Our preliminary studies have showed our ability to develop a stable, reproducible inhaled H2S toxic rabbit model; which will help us detect the outcomes of H2S toxicity, monitor response to treatments with various experimental potential antidote agents, and ultimately develop a specific antidote for this highly lethal gas. CLINICAL IMPLICATIONS: simulating H2S inhalation exposure to develop an antidote DISCLOSURES: No relevant relationships by vikhyat bebarta, source=Web Response No relevant relationships by Gerry Boss, source=Web Response No relevant relationships by Matthew Brenner, source=Admin input No relevant relationships by Tanya Burney, source=Web Response No relevant relationships by Jangwoen Lee, source=Web Response No relevant relationships by Sari Mahon, source=Web Response No relevant relationships by David Mukai, source=Web Response No relevant relationships by Tina Saber, source=Web Response No relevant relationships by Mayer Saidian, source=Web Response

Hydrogen sulfide inhalation-induced immune damage is involved in oxidative stress, inflammation, apoptosis and the Th1/Th2 imbalance in broiler bursa of Fabricius

Hydrogen sulfide (H2S) is widely accepted to be a signaling molecule that exhibits some potentially beneficial therapeutic effects at physiological concentrations. At elevated levels, H2S is highly toxic and has a negative effect on human health and animal welfare. Studies have shown that H2S exposure induces an immune function in mice, but there are few studies of the effect of continuous H2S exposure on immune organs in poultry. In this study, one-day-old broilers were selected and exposed to 4 or 20 ppm of H2S gas for 14, 28 and 42 days of age. After exposure, the bursa of Fabricius (BF) was harvested. The results showed that continuous H2S exposure reduced the body weight, abdominal fat percentage, and antibody titer in broilers. H2S exposure also decreased mRNA expression of IgA, IgM and IgG in the broiler BF. A histological study revealed obvious nuclear debris, and a few vacuoles in the BF, and an ultrastructural study revealed mitochondrial and nuclear damage to BF cells after H2S exposure for 42 d. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay suggested H2S exposure remarkably increased the number of TUNEL positive nuclei and significantly increased apoptotic index. The expression of apoptotic genes also confirmed that H2S inhalation damaged the broiler BF. Increased cytokines and reduced antioxidant responses were detected in the BF after exposure to H2S. Cytokines promoted inflammation and caused a Th1/Th2 imbalance. We suggest that continuous H2S intoxication triggers oxidative stress, inflammation, apoptosis and a Th1/Th2 imbalance in the BF, leading to immune injury in broilers.

Sulfide Toxicity and Its Modulation by Nitric Oxide in Bovine Pulmonary Artery Endothelial Cells.

Bovine pulmonary artery endothelial cells (BPAEC) respond in a dose-dependent manner to millimolar (0-10) levels of sodium sulfide (NaHS). No measurable increase in caspase-3 activity and no change in the extent of autophagy (or mitophagy) were observed in BPAEC. However, lactate dehydrogenase levels increased in the BPAEC exposed NaHS, which indicated necrotic cell death. In the case of galactose-conditioned BPAEC, the toxicity of NaHS was increased by 30% compared to that observed in BPAEC maintained in the regular glucose-containing culture medium, which indicated a link between mitochondrial oxidative phosphorylation and the mechanism of toxicant action. This is consistent with the widely held view that cytochrome c oxidase (complex IV of the mitochondrial electron-transport system) is the principal molecular target involved in the acute toxicity of "sulfide" (H2S/HS-). In support of this view, elevated NO (which can reverse cytochrome c oxidase inhibition) ameliorated the toxicity of NaHS and, conversely, suppression of endogenous NO production exacerbated the observed toxicity. Respirometric measurements showed the BPAEC to possess a robust sulfide oxidizing system, which was able to out-compete cytochrome c oxidase for available H2S/HS- at micromolar concentrations. This detoxification system has previously been reported by other groups in several cell types, but notably, not neurons. The findings appear to provide some insight into the question of why human survivors of H2S inhalation frequently present at the clinic with respiratory insufficiency/pulmonary edema, while acutely poisoned laboratory animals tend to either succumb to cardiopulmonary paralysis or fully recover without any intervention.

Hydrogen Sulfide Exerts Anti-oxidative and Anti-inflammatory Effects in Acute Lung Injury.

Acute lung injury (ALI) caused by septic stimuli is still a major problem in critical care patients. We have shown previously that hydrogen sulfide (H2S) mediates anti-inflammatory and lung protective effects. In the present study, we aimed to investigate the underlying mechanisms. C57BL/6N mice were instilled with lipopolysaccharide (LPS) intranasally in the absence or presence of inhaled H2S for 6h. LPS instillation led to alveolar wall thickening, an elevated ALI score, increased neutrophil transmigration, and elevated interleukin-1β cytokine release into the bronchoalveolar lavage fluid. In contrast, H2S inhalation prevented lung injury and inflammation despite LPS treatment. Moreover, H2S inhalation significantly inhibited protein expression of cystathionine-β-synthetase, heat shock protein 70, phosphorylated p38 MAP kinase, NADPH oxidase 2, and the formation of reactive oxygen species (ROS) in LPS-challenged animals. In conclusion, H2S prevents LPS-induced ALI by inhibition of pro-inflammatory and oxidative responses via the concerted attenuation of stress protein, MAP kinase, and ROS signaling pathways.