The noble gas helium has many applications owing to its distinct physical and chemical characteristics, namely: its low density, low solubility, and high thermal conductivity. Chiefly, the abundance of studies in medicine relating to helium are concentrated in its possibility of being used as an adjunct therapy in a number of respiratory ailments such as asthma exacerbation, COPD, ARDS, croup, and bronchiolitis. Helium gas, once believed to be biologically inert, has been recently shown to be beneficial in protecting the myocardium from ischemia by various mechanisms. Though neuroprotection of brain tissue has been documented, the mechanism by which it does so has yet to be made clear. Surgeons are exploring using helium instead of carbon dioxide to insufflate the abdomen of patients undergoing laparoscopic abdominal procedures due to its superiority in preventing respiratory acidosis in patients with comorbid conditions that cause carbon dioxide retention. Newly discovered applications in Pulmonary MRI radiology and imaging of organs in very fine detail using Helium Ion Microscopy has opened exciting new possibilities for the use of helium gas in technologically advanced fields of medicine.
Helium; Heliox; Inhalation therapy; Cardioprotection; Neuroprotection; Insufflation
Research of medical gases is well established in Poland and has been marked with the foundation of several professional societies. Numerous academic centers including those dealing with hyperbaric and diving medicine conduct studies of medical gases, in vast majority supported with intramural funds. In general, Polish research of medical gases is very much clinical in nature, covering new applications and safety of medical gases in medicine; on the other hand there are several academic centers pursuing preclinical studies, and elaborating basic theories of gas physiology and mathematical modeling of gas exchange. What dominates is research dealing with oxygen and ozone as well as studies of anesthetic gases and their applications. Finally, several research directions involving noble gas, hydrogen and hydrogen sulfide for cell protection, only begin to gain recognition of basic scientists and clinicians. However, further developments require more monetary spending on research and clinical testing as well as formation of new collective bodies for coordinating efforts in this matter.
Oxygen; Ozone; Gaseous transmitters; Volatile anesthetics; Noble gas; Poland
Volatile anesthetics have been the major anesthetics used clinically for more than 150 years. They provide all components of general anesthesia and are easy to be applied and monitored with modern equipment and technology. In addition to having anesthetic property, volatile anesthetics have multiple other effects. Many studies have clearly shown that volatile anesthetics can reduce systemic and local inflammatory responses induced by various stimuli in humans and animals. On the other hand, recent animal studies have shown that volatile anesthetics may induce mild neuroinflammation. These dual effects on inflammation may have significant biological implications and are briefly reviewed here.
Following radiotherapy, many patients with osteoradionecrosis suffer from xerostomia, thereby decreasing their quality of life. Patients can develop problems with speech, eating, increased dental caries, dysphagia, fractured dentition, chronic refractory osteomyelitis and osteoradionecrosis. Symptoms associated with salivary gland dysfunction can be severe enough that patients terminate the course of their radiotherapy prematurely due to the decrease in their quality of life. Currently, the only treatments available to patients are palliative. A definitive treatment has yet to be discovered. Head and neck cancers, which comprise 5% of overall cancer treatments, rank 8th most expensive to treat in the United States today. Hyperbaric oxygen is being considered for the therapy of radiated salivary glands because it has been shown to stimulate capillary angiogenesis and fibroplasia in radiation treated tissues. It has been hypothesized that salivary acinar cells undergo apoptosis following radiation therapy. The purpose of this paper is to discuss the mechanisms of salivary gland injury and evaluate whether hyperbaric oxygen therapy improves salivary gland function in patients who develop xerostomia and osteoradionecrosis following head and neck radiation.
Osteoradionecrosis; Xerostomia; Saliva; Hyperbaric Oxygen Therapy
Oxidative stress (OS) related to glucose degradation products such as methylglyoxal is reportedly associated with peritoneal deterioration in patients treated with peritoneal dialysis (PD). However, the use of general antioxidant agents is limited due to their harmful effects. This study aimed to clarify the influence of the novel antioxidant molecular hydrogen (H2) on peritoneal OS using albumin redox state as a marker.
Effluent and blood samples of 6 regular PD patients were obtained during the peritoneal equilibrium test using standard dialysate and hydrogen-enriched dialysate. The redox state of albumin in effluent and blood was determined using high-performance liquid chromatography.
Mean proportion of reduced albumin (ƒ(HMA)) in effluent was significantly higher in H2-enriched dialysate (62.31 ± 11.10%) than in standard dialysate (54.70 ± 13.08%). Likewise, serum ƒ(HMA) after administration of hydrogen-enriched dialysate (65.75 ± 7.52%) was significantly higher than that after standard dialysate (62.44 ± 7.66%).
Trans-peritoneal administration of H2 reduces peritoneal and systemic OS.
Molecular hydrogen; Oxidative stress; Albumin redox state; Peritoneal dialysis
Most of the results regarding hydrogen (H2) therapy for acute cerebral ischemia are derived from in vitro studies and animal experiments, with only a few obtained from human trials with a limited number of subjects. Thus, there is a paucity of information regarding both the beneficial therapeutic effects as well as the side effects of H2 on acute cerebral ischemia in humans. We designed a pilot study to investigate single dose intravenous H2-administration in combination with edaravone, aiming to provide an initial estimate of the possible risks and benefits in select patients presenting with acute ischemic stroke.
An open-label, prospective, non-randomized study of intravenous H2-administration was performed in 38 patients hospitalized for acute ischemic stroke. All patients received an H2-enriched intravenous solution in addition to edaravone immediately after the diagnosis of acute ischemic stroke. Acute stroke patients within 3 h of onset received intravenous tissue plasminogen activator (t-PA) (0.6 mg/kg) treatment, and patients receiving t-PA had to commence the administration of the H2-enriched intravenous solution and edaravone before or at the same time as the t-PA was infused.
Complications were observed in 2 patients (5.3%), which consisted of diarrhea in 1 patient (2.6%) and cardiac failure in 1 patient (2.6%). No deterioration in laboratory tests, urinary tests, ECG, or chest X-ray radiograms occurred in any patient in this study. In all patients, the mean National Institutes of Health Stroke Scale (NIHSS) scores at baseline, and 7, 30, and 90 d after admission were 8.2 ± 7.5, 5.6 ± 7.1, 4.9 ± 6.5, and 4.5 ± 6.3, respectively. The early recanalization was identified in 4 of 11 patients (36.4%) who received intravenous t-PA administration. Hemorrhagic transformation was observed in 2 patients (18.2%). None of the patients in this study that were treated with t-PA developed symptomatic intracranial hemorrhage.
Data from the current study indicate that an H2-enriched intravenous solution is safe for patients with acute cerebral infarction, including patients treated with t-PA.
Acute ischemic stroke; Edaravone; Free radical scavenger; Hydrogen; Reactive oxygen species; Safety; Tissue plasminogen activator
High costs still limits the widespread use of xenon in the clinical practice. Therefore, we evaluated xenon consumption of different delivery modes during general surgery.
A total of 48 patients that underwent general surgery with balanced xenon anaesthesia were retrospectively analysed according to the mode of xenon delivery during maintenance phase (ECO mode, AUTO mode or MANUAL mode).
Xenon consumption was highest during the wash-in phase (9.4 ± 2.1l) and further decreased throughout maintenance of anaesthesia. Comparison of different xenon delivery modes revealed significant reduced xenon consumption during ECO mode (18.5 ± 3.7L (ECO) vs. 24.7 ± 11.5L (AUTO) vs. 29.6 ± 14.3L (MANUAL); p = 0.033). No differences could be detected with regard to anaesthetic depth, oxygenation or performance of anaesthesia.
The closed-circuit respirator Felix Dual offers effective reduction of xenon consumption during general surgery when ECO mode is used.
Anaesthesia; Xenon; Closed-circuit respirator
Hydrogen gas is a bioactive molecule that has a diversity of effects, including anti-apoptotic, anti-inflammatory and anti-oxidative properties; these overlap with the process of neuroprogression in major psychiatric disorders. Specifically, both bipolar disorder and schizophrenia are associated with increased oxidative and inflammatory stress. Moreover, lithium which is commonly administered for treating bipolar disorder has effects on oxidative stress and apoptotic pathways, as do valproate and some atypical antipsychotics for treating schizophrenia. Molecular hydrogen has been studied pre-clinically in animal models for the treatment of some medical conditions including hypoxia and neurodegenerative disorders, and there are intriguing clinical findings in neurological disorders including Parkinson’s disease. Therefore, it is hypothesized that administration of hydrogen molecule may have potential as a novel therapy for bipolar disorder, schizophrenia, and other concurrent disorders characterized by oxidative, inflammatory and apoptotic dysregulation.
Studies on molecular hydrogen have evolved tremendously from its humble beginnings and have continued to change throughout the years. Hydrogen is extremely unique since it has the capability to act at the cellular level. Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell. Hydrogen is most commonly applied as a gas, water, saline, and can be applied in a variety of other mediums. There are also few side effects involving hydrogen, thus making hydrogen a perfect medical gas candidate for the convention of novel therapeutic strategies against cardiovascular, cerebrovascular, cancer, metabolic, and respiratory diseases and disorders. Although hydrogen appears to be faultless at times, there still are several deficiencies or snares that need to be investigated by future studies. This review article seeks to delve and comprehensively analyze the research and experiments that alludes to molecular hydrogen being a novel therapeutic treatment that medicine desperately needs.
Antioxidant; Cytoprotection; Hydrogen therapy; Mechanisms; Reactive oxygen species
Hyperbaric oxygen therapy (HBOT), referring to the medical use of oxygen at a level higher than atmospheric pressure, exerts neuroprotective effects after ischemic stroke via various mechanisms. It has been demonstrated that HBOT modulates the synthesis and degradation of hormones. Leptin, an adipose derived hormone, has been found to confer neuroprotection following experimental stroke. However, it is not known whether HBOT alters leptin concentrations after permanent middle cerebral artery occlusion (pMCAo) in the rat. In this present study, we aimed to investigate the effect of HBOT on the serum concentration of leptin in rats subjected to pMCAo. HBOT was initiated 48 hrs after experimental pMCAo, at 2.5 atmospheres absolutes with 100% oxygen, 1 hr a day for 10 consecutive days. Body weight, neurobehavioral deficits and infarct size were evaluated. Blood was collected on day 1 and day 16 following HBOT. Serum leptin concentrations were measured with ELISA. Delayed HBOT reduced infarct size and improved neurobehavioral scores. Decreased serum levels of leptin were found in treated and untreated pMCAo animals, compared to the sham group on day 1 (P > 0.05) and day 16 (P < 0.05). However, no statistical significance was found between HBOT and the air group. We concluded that the neuroprotective effects of delayed HBOT in pMCAo rats were unlikely to be exerted through changes in the serum concentration of leptin.
Hyperbaric oxygen therapy; Leptin; Neuroprotection; MCAo; Rats
The articles contained in this review series exemplify the diverse applications and succinct biological relevance of this simple gas. Articles summarizing the important effects of carbon monoxide in preventing the rejection of an organ, in its neuroprotective properties in piglets, regulation of mycobacterial growth, in its anti-inflammatory effects in the gut and in its use in new and innovative modalities and avenues by which to harness adjuvant therapies are eloquently and precisely described and reviewed. Each of these reports offers but a glimpse of continued prudent and sound evidence that this simple diatomic gas offers astonishingly potent and extremely diverse biological and medicinal qualities.
There is accumulating evidence that obesity is closely associated with an impaired free fatty acid metabolism as well as with insulin resistance and inflammation. Excessive fatty acid uptake mediated by fatty acid translocase CD36 plays an important role in hepatic steatosis. Molecular hydrogen has been shown to attenuate oxidative stress and improve lipid, glucose and energy metabolism in patients and animal models of hepatic steatosis and atherosclerosis, but the underlying molecular mechanisms remain largely unknown.
Human hepatoma HepG2 cells were exposed to palmitate-BSA complex after treatment with or without hydrogen for 24 h. The fatty acid uptake was measured by using spectrofluorometry and the lipid content was detected by Oil Red O staining. JNK phosphorylation and CD36 expression were analyzed by Western blot and real-time PCR analyses.
Pretreatment with hydrogen reduced fatty acid uptake and lipid accumulation after palmitate overload in HepG2 cells, which was associated with inhibition of JNK activation. Hydrogen treatment did not alter CD36 mRNA expression but reduced CD36 protein expression.
Hydrogen inhibits fatty acid uptake and lipid accumulation through the downregulation of CD36 at the protein level in hepatic cultured cells, providing insights into the molecular mechanism underlying the hydrogen effects in vivo on lipid metabolism disorders.
Molecular hydrogen; HepG2 cells; Fatty acid; JNK; Phosphorylation; CD36; Hepatic steatosis
A great deal of interest has been paid recently to the hydrogen sulfide, the newest member of the gasotransmitter family. With the growing interest in the biology of H2S, the need for meetings and conferences dedicated solely to the field of H2S has also grown. In 2009, scientist from around the world met in Shanghai, China for the first time to discuss the physiological relevance of H2S. In 2012, two conferences were organized to bring scientists, clinicians, and industry representatives together to discuss the latest breakthroughs concerning the emergent field of H2S. The following is a summary report of The First European Conference on the Biology of Hydrogen Sulfide and the Second International Conference on Hydrogen Sulfide Biology and Medicine.
Gasotransmitter; Hydrogen sulfide; Nitric oxide; Carbon monoxide
Xenon is a medical gas capable of establishing neuroprotection, inducing anesthesia as well as serving in modern laser technology and nuclear medicine as a contrast agent. In spite of its high cost, its lack of side effects, safe cardiovascular and organoprotective profile and effective neuroprotective role after hypoxic-ischemic injury (HI) favor its applications in clinics. Xenon performs its anesthetic and neuroprotective functions through binding to glycine site of glutamatergic N-methyl-D-aspartate (NMDA) receptor competitively and blocking it. This blockage inhibits the overstimulation of NMDA receptors, thus preventing their following downstream calcium accumulating cascades. Xenon is also used in combination therapies together with hypothermia or sevoflurane. The neuroprotective effects of xenon and hypothermia cooperate synergistically whether they are applied synchronously or asynchronously. Distinguishing properties of Xenon promise for innovations in medical gas field once further studies are fulfilled and Xenon’s high cost is overcome.
Xenon; Hypoxia; Ischemia; Neuroprotection; Anesthesia; Hypothermia; NMDA
Xenon is one of noble gases and has been recognized as an anesthetic for more than 50 years. Xenon possesses many of the characteristics of an ideal anesthetic, but it is not widely applied in clinical practice mainly because of its high cost. In recent years, numerous studies have demonstrated that xenon as an anesthetic can exert neuroprotective and cardioprotective effects in different models. Moreover, xenon has been applied in the preconditioning, and the neuroprotective and cardioprotective effects of xenon preconditioning have been investigated in a lot of studies in which some mechanisms related to these protections are proposed. In this review, we summarized these mechanisms and the biological effects of xenon preconditioning.
Xenon; Preconditioning; Neuroprotection; Cardioprotection; Mechanism
Stroke is a leading cause of death and disability due to disturbance of blood supply to the brain. As brain is highly sensitive to hypoxia, insufficient oxygen supply is a critical event contributing to ischemic brain injury. Normobaric hyperoxia (NBO) that aims to enhance oxygen delivery to hypoxic tissues has long been considered as a logical neuroprotective therapy for ischemic stroke. To date, many possible mechanisms have been reported to elucidate NBO’s neuroprotection, such as improving tissue oxygenation, increasing cerebral blood flow, reducing oxidative stress and protecting the blood brain barrier. As ischemic stroke triggers a battery of damaging events, combining NBO with other agents or treatments that target multiple mechanisms of injury may achieve better outcome than individual treatment alone. More importantly, time loss is brain loss in acute cerebral ischemia. NBO can be a rapid therapy to attenuate or slow down the evolution of ischemic tissues towards necrosis and therefore “buy time” for reperfusion therapies. This article summarizes the current literatures on NBO as a simple, widely accessible, and potentially cost-effective therapeutic strategy for treatment of acute ischemic stroke.
Oxygen; Ischemia; Oxidative stress; Blood brain barrier; Reperfusion; Blood flow; Neuroprotection
The number of organ and tissue transplants has increased worldwide in recent decades. However, graft rejection, infections due to the use of immunosuppressive drugs and a shortage of graft donors remain major concerns. Carbon monoxide (CO) had long been regarded solely as a poisonous gas. Ultimately, physiological studies unveiled the endogenous production of CO, particularly by the heme oxygenase (HO)-1 enzyme, recognizing CO as a beneficial gas when used at therapeutic doses. The protective properties of CO led researchers to develop uses for it, resulting in devices and molecules that can deliver CO in vitro and in vivo. The resulting interest in clinical investigations was immediate. Studies regarding the CO/HO-1 modulation of immune responses and their effects on various immune disorders gave rise to transplantation research, where CO was shown to be essential in the protection against organ rejection in animal models. This review provides a perspective of how CO modulates the immune system to improve transplantation and suggests its use as a therapy in the field.
CO; HO-1; Immune response; Transplant
Studies in animal models show that the primary mechanism by which heme-oxygenases impart beneficial effects is due to the gaseous molecule carbon monoxide (CO). Produced in humans mainly by the catabolism of heme by heme-oxygenase, CO is a neurotransmitter important for multiple neurologic functions and affects several intracellular pathways as a regulatory molecule. Exogenous administration of inhaled CO or carbon monoxide releasing molecules (CORM’s) impart similar neurophysiological responses as the endogenous gas. Its’ involvement in important neuronal functions suggests that regulation of CO synthesis and biochemical properties may be clinically relevant to neuroprotection and the key may be a change in metabolic substrate from glucose to lactate. Currently, the drug is under development as a therapeutic agent and safety studies in humans evaluating the safety and tolerability of inhaled doses of CO show no clinically important abnormalities, effects, or changes over time in laboratory safety variables. As an important therapeutic option, inhaled CO has entered clinical trials and its clinical role as a neuroprotective and neurotherapeutic agent has been suggested. In this article, we review the neuroprotective effects of endogenous CO and discuss exogenous CO as a neuroprotective and neurotherapeutic agent.
The intracellular pathogen Mycobacterium tuberculosis (Mtb) is exposed to multiple host antimicrobial pathways, including toxic gases such as superoxide, nitric oxide and carbon monoxide (CO). To survive, mycobacteria evolved mechanisms to resist the toxic environment, and in this review we focus on a relatively new field, namely, the role of macrophage heme oxygenase and its enzymatic product CO in Mtb pathogenesis. In particular, we focus on (i) the induction of heme oxygenase during Mtb infection and its relevance to Mtb pathogenesis, (ii) the ability of mycobacteria to catabolize CO, (iii) the transcriptional reprogramming of Mtb by exposure to CO, (iv) the general antimicrobial properties of CO and (v) new genetic evidence characterizing the ability of Mtb to resist CO toxicity. Developing a complete molecular and genetic understanding of the pathogenesis of Mtb is essential to its eventual eradication.
Carbon monoxide; Heme oxygenase; Microbiology; Immunology; Mycobacterium tuberculosis; Microbial pathogenesis
Inhalation of low-density helium/oxygen mixtures has been used both to lower the airway resistance and work of breathing of patients with obstructive lung disease and to transport pharmaceutical aerosols to obstructed lung regions. However, recent clinical investigations have highlighted the potential for entrainment of room air to dilute helium/oxygen mixtures delivered through non-rebreather facemasks, thereby increasing the density of the inhaled gas mixture and limiting intended therapeutic effects. This article describes the development of benchtop methods using face models for evaluating delivery of helium/oxygen mixtures through facemasks.
Four face models were used: a flat plate, a glass head manikin, and two face manikins normally used in life support training. A mechanical test lung and ventilator were employed to simulate spontaneous breathing during delivery of 78/22 %vol helium/oxygen through non-rebreather facemasks. Based on comparison of inhaled helium concentrations with available clinical data, one face model was selected for measurements made during delivery of 78/22 or 65/35 %vol helium/oxygen through three different masks as tidal volume varied between 500 and 750 ml, respiratory rate between 14 and 30 breaths/min, the inspiratory/expiratory ratio between 1/2 and 1/1, and the supply gas flow rate between 4 and 15 l/min. Inhaled helium concentrations were measured both with a thermal conductivity analyzer and using a novel flow resistance method.
Face models borrowed from life support training provided reasonably good agreement with available clinical data. After normalizing for the concentration of helium in the supply gas, no difference was noted in the extent of room air entrainment when delivering 78/22 versus 65/35 %vol helium/oxygen. For a given mask fitted to the face in a reproducible manner, delivered helium concentrations were primarily determined by the ratio of supply gas flow rate to simulated patient minute ventilation, with the inspiratory/expiratory ratio playing a secondary role. However, the functional dependence of helium concentration on these two ratios depended on the mask design.
Large differences in mask performance were identified. With continued refinement, the availability of reliable benchtop methods is expected to assist in the development and selection of patient interfaces for delivery of helium/oxygen and other medical gases.
Facemask; Patient Interface; Helium; Oxygen; Heliox; Bench testing; Test lung; Face model; Head model; Manikin
In this editorial, the issues related to the hyperbaric oxygen therapy and its utility in managing cerebral vasospasm in patients with subarachnoid hemorrhage is discussed.
Oxygen; Cerebral vasospasm; Subarachnoid hemorrhage
Carbon monoxide-releasing molecules (CO-RMs) are a class of organometallo compounds capable of delivering controlled quantities of CO gas to cells and tissues thus exerting a broad spectrum of pharmacological effects. CO-RMs containing transition metal carbonyls were initially implemented to mimic the function of heme oxygenase-1 (HMOX1), a stress inducible defensive protein that degrades heme to CO and biliverdin leading to anti-oxidant and anti-inflammatory actions. Ten years after their discovery, the research on the chemistry and biological activities of CO-RMs has greatly intensified indicating that their potential use as CO delivering agents for the treatment of several pathological conditions is feasible. Although CO-RMs are a class of compounds that structurally diverge from traditional organic-like pharmaceuticals, their behaviour in the biological environments is progressively being elucidated revealing interesting features of metal-carbonyl chemistry towards cellular targets. Specifically, the presence of carbonyl groups bound to transition metals such as ruthenium, iron or manganese appears to make CO-RMs unique in their ability to transfer CO intracellularly and amplify the mechanisms of signal transduction mediated by CO. In addition to their well-established vasodilatory activities and protective effects against organ ischemic damage, CO-RMs are emerging for their striking anti-inflammatory properties which may be the result of the multiple activities of metal carbonyls in the control of redox signaling, oxidative stress and cellular respiration. Here, we review evidence on the pharmacological effects of CO-RMs in models of acute and chronic inflammation elaborating on some emerging concepts that may help to explain the chemical reactivity and mechanism(s) of action of this distinctive class of compounds in biological systems.
Inflammation; Carbon monoxide-releasing molecules (CO-RMs); Oxidative stress; Inflammatory mediators; Bactericidal activities
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of bone and cartilage. Although its etiology is unknown, the hydroxyl radical has been suggested to be involved in the pathogenesis of RA. Recently, molecular hydrogen (H2) was demonstrated to be a selective scavenger for the hydroxyl radical. Also, the method to prepare water containing extremely high concentration of H2 has been developed. We hypothesized that H2 in the water could complement conventional therapy by reducing the oxidative stress in RA.
Twenty patients with rheumatoid arthritis (RA) drank 530 ml of water containing 4 to 5 ppm molecular hydrogen (high H2 water) every day for 4 weeks. After a 4-week wash-out period, the patients drank the high H2 water for another 4 weeks. Urinary 8-hydroxydeoxyguanine (8-OHdG) and disease activity (DAS28, using C-reactive protein [CRP] levels) was estimated at the end of each 4-week period.
Drinking high H2 water seems to raise the concentration of H2 more than the H2 saturated (1.6 ppm) water in vivo. Urinary 8-OHdG was significantly reduced by 14.3% (p < 0.01) on average. DAS28 also decreased from 3.83 to 3.02 (p < 0.01) during the same period. After the wash-out period, both the urinary 8-OHdG and the mean DAS28 decreased, compared to the end of the drinking period. During the second drinking period, the mean DAS28 was reduced from 2.83 to 2.26 (p < 0.01). Urinary 8-OHdG was not further reduced but remained below the baseline value. All the 5 patients with early RA (duration < 12 months) who did not show antibodies against cyclic citrullinated peptides (ACPAs) achieved remission, and 4 of them became symptom-free at the end of the study.
The results suggest that the hydroxyl radical scavenger H2 effectively reduces oxidative stress in patients with this condition. The symptoms of RA were significantly improved with high H2 water.
Arthritis, Rheumatoid; Oxidative stress; Reactive oxygen species; Molecular hydrogen; 8-hydroxylguanine; Hydroxyl radical: DNA repair; Error protein
Local pulmonary and systemic infections can lead to acute lung injury (ALI). The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality. Hydrogen sulfide (H2S) appears to represent a new therapeutic approach to ALI. The gas has been shown to mediate potent anti-inflammatory and organ protective effects in vivo. This study was designed to define its potentially protective role in sepsis-induced lung injury.
C57BL/6 N mice received lipopolysaccharide (LPS) intranasally in the absence or presence of 80 parts per million H2S. After 6 h, acute lung injury was determined by comparative histology. Bronchoalveolar lavage (BAL) fluid was analyzed for total protein content and differential cell counting. BAL and serum were further analyzed for interleukin-1β, macrophage inflammatory protein-2, and/or myeloperoxidase glycoprotein levels by enzyme-linked immunosorbent assays. Differences between groups were analyzed by one way analysis of variance.
Histological analysis revealed that LPS instillation led to increased alveolar wall thickening, cellular infiltration, and to an elevated ALI score. In the presence of H2S these changes were not observed despite LPS treatment. Moreover, neutrophil influx, and pro-inflammatory cytokine release were enhanced in BAL fluid of LPS-treated mice, but comparable to control levels in H2S treated mice. In addition, myeloperoxidase levels were increased in serum after LPS challenge and this was prevented by H2S inhalation.
Inhalation of hydrogen sulfide protects against LPS-induced acute lung injury by attenuating pro-inflammatory responses.
Acute lung injury; Hydrogen sulfide; Sepsis; Lipopolysaccharide; Inflammation
Methane is an attractive fuel. Biologically, methanogens in the colon can use carbon dioxide and hydrogen to produce methane as a by-product. It was previously considered that methane is not utilized by humans. However, in a recent study, results demonstrated that methane could exert anti-inflammatory effects in a dog small intestinal ischemia-reperfusion model.
Point of view
Actually, the bioactivity of methane has been investigated in gastrointestinal diseases, but the exact mechanism underlying the anti-inflammatory effects is required to be further elucidated. Methane can cross the membrane and is easy to collect due to its abundance in natural gas. Although methane is flammable, saline rich in methane can be prepared for clinical use. These seem to be good news in application of methane as a therapeutic gas.
Several problems should be resolved before its wide application in clinical practice.
Methane; Anti-inflammation; Therapeutic gas; Methanogen