Therapeutic Effects of Hydrogen Gas Inhalation on Trimethyltin-Induced Neurotoxicity and Cognitive Impairment in the C57BL/6 Mice Model

Oxidative stress (OS) is one of the causative factors in the pathogenesis of various neurodegenerative diseases, including Alzheimer’s disease (AD) and cognitive dysfunction. In the present study, we investigated the effects of hydrogen (H2) gas inhalation in trimethyltin (TMT)-induced neurotoxicity and cognitive dysfunction in the C57BL/6 mice. First, mice were divided into the following groups: mice without TMT injection (NC), TMT-only injection group (TMT only), TMT injection + lithium chloride-treated group as a positive control (PC), and TMT injection + 2% H2 inhalation-treated group (H2). The TMT injection groups were administered a single dosage of intraperitoneal TMT injection (2.6 mg/kg body weight) and the H2 group was treated with 2% H2 for 30 min once a day for four weeks. Additionally, a behavioral test was performed with Y-maze to test the cognitive abilities of the mice. Furthermore, multiple OS- and AD-related biomarkers such as reactive oxygen species (ROS), nitric oxide (NO), calcium (Ca2+), malondialdehyde (MDA), glutathione peroxidase (GPx), catalase, inflammatory cytokines, apolipoprotein E (Apo-E), amyloid β (Aβ)-40, phospho-tau (p-tau), Bcl-2, and Bcl-2- associated X (Bax) were investigated in the blood and brain. Our results demonstrated that TMT exposure alters seizure and spatial recognition memory. However, after H2 treatment, memory deficits were ameliorated. H2 treatment also decreased AD-related biomarkers, such as Apo-E, Aβ-40, p-tau, and Bax and OS markers such as ROS, NO, Ca2+, and MDA in both serum and brain. In contrast, catalase and GPx activities were significantly increased in the TMT-only group and decreased after H2 gas treatment in serum and brain. In addition, inflammatory cytokines such as granulocyte colony-stimulating factors (G-CSF), interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) were found to be significantly decreased after H2 treatment in both serum and brain lysates. In contrast, Bcl-2 and vascular endothelial growth factor (VEGF) expression levels were found to be enhanced after H2 treatment. Taken together, our results demonstrated that 2% H2 gas inhalation in TMT-treated mice exhibits memory enhancing activity and decreases the AD, OS, and inflammatory-related markers. Therefore, H2 might be a candidate for repairing neurodegenerative diseases with cognitive dysfunction. However, further mechanistic studies are needed to fully clarify the effects of H2 inhalation on TMT-induced neurotoxicity and cognitive dysfunction.

Rapid Successful Management of Diffuse Alveolar Hemorrhage as the Primary Presentation of Chlorine Gas Inhalation: A Rare Case Report

Chlorine-containing bleach, as a common disinfectant, can cause mild to severe symptoms from nasal irritation to life-threatening conditions such as acute respiratory distress syndrome (ARDS). However, the toxicity level of chlorine gas depends on the duration and concentration of exposure. Herein, we describe the case of a 44-year-old man admitted to the emergency department with a chief complaint of severe shortness of breathing and hemoptysis following accidental, short-time exposure to chlorine-containing bleach. Because of the life-threatening condition, he was transferred to the Intensive Care Unit (ICU) and received mechanical ventilation along with a corticosteroid agent and antibiotic therapy. Despite limited data on management of the severe complications of the exposure, the patient successfully recovered after four days.

Effect of hydrogen gas inhalation on patient QOL after hepatectomy: protocol for a randomized controlled trial

Introduction Molecular hydrogen had been considered inactive in vivo but is an antioxidant that selectively reduces highly toxic reactive oxygen species (ROS). Animal studies have reported that hydrogen gas inhalation helped alleviate cerebral and cardiac ischemia-reperfusion injuries. In humans, hydrogen inhalation therapy is presently approved as a treatment under Advanced Medical Care B in Japan (jRCTs031180352: limited to adult patients who suffered out-of-hospital cardiac arrest and are in a continuous coma) and its effectiveness is being examined in a clinical trial. The Japanese government has introduced the “Advanced Medical Care System” to promote the development of drugs and devices under governmental regulations. Advanced Medical Care B is a system designed for unapproved or off-label drugs or medical technologies used in a clinical trial setting. Hepatectomy is generally performed with repeated hepatic blood-flow occlusion and then reperfusion (ischemia and reperfusion). No report, however, has been made on ROS inhibition by hydrogen inhalation therapy or its effectiveness in post-hepatectomy patients. Hydrogen gas inhalation in the early stages after hepatectomy is anticipated to inhibit liver dysfunction by inhibiting ROS. Methods and analysis This study is a randomized, controlled, double-blind superiority trial, which will be conducted as a “specified clinical trial” in accordance with the Clinical Trials Act in Japan. Trial registration was prospectively completed before the first participant was enrolled. The subjects will be patients who will undergo hepatectomy and will be allocated randomly into group A with hydrogen gas inhalation or group B with air inhalation after hepatectomy. The study will examine if hydrogen gas inhalation improves QOL of post-hepatectomy patients. The primary endpoint is patient QOL (score of a 40-item quality of recovery questionnaire, QoR40) on postoperative day 3 and the secondary endpoints are QoR40s besides that on postoperative day 3, grade of postoperative complications (Clavien-Dindo score), level of pain (Numerical Rating Scale (NRS)), amount of dietary intake, liver function, inflammation level, 8-hydroxydeoxyguanosine (urinary 8-OHdG) level, and number of pedometer-assessed steps. Ethics and dissemination The study protocol has been approved by the Niigata University Central Review Board of Clinical Research. The findings of this study will be widely disseminated through peer-reviewed publications and conference presentations. Trial registration jRCTs 03220332. Registered on 21 January 2021

A Comparison of the Antioxidant Effects Between Hydrogen Gas Inhalation and Vitamin C Supplementation in Response to a 60-Min Treadmill Exercise in Rat Gastrocnemius Muscle

The reactive oxygen species (ROS) produced during exercise act as a double-edged sword because they may cause oxidative damage but also play a role in the signaling pathways. A supplementation of exogenous antioxidants can reduce the total amount of ROS during exercise while it may also affect the ROS’ role in the signaling pathways of mitochondrial biogenesis. It has been suggested that hydrogen gas, as an antioxidant, can selectively scavenge hydroxyl radicals but does not affect superoxide anion’s signal transduction. The aim of this study was to compare the effects of 1-h hydrogen gas inhalation 30min prior to a treadmill exercise on the key biomarkers of mitochondrial biogenesis and related signaling pathways, and the activities of endogenous antioxidant enzymes, with those of vitamin C, in the rat skeletal muscle. Eighty-one 8-week-old male Sprague–Dawley (SD) rats were randomly assigned to three interventions (exercise-only, exercise+4%H2, and exercise+vitamin C at 500mg/kg weight, with 27 rats under each intervention), and sampled at pre-, immediately post and 4h post a 60-min treadmill exercise at speed of 27m/min and flat inclination, with nine rats in each sub-group. Expression of mitochondrial biogenetic markers and related signaling molecules in gastrocnemius muscle, and concentrations of oxidative stress markers in serum were measured. Two-way ANOVA or Kruskal–Wallis analyses showed that both hydrogen inhalation and vitamin C supplementation significantly reduced serum levels of MDA immediately after exercise and AGEs 4h after exercise. The pre-exercise supplement of vitamin C significantly reduced mitochondrial complex IV concentrations and PGC-1α, NRF-1, TFAM gene expression levels compared to the pre-exercise group, but the hydrogen gas intervention did not result in a reduction in these measurements. Unlike vitamin C, hydrogen inhalation did not blunt post-exercise mitochondrial biogenetic signals, but resulted in an increase in complex IV concentration, activation of PGC-1α, and TFAM and NRF-2 gene transcription, and up-regulation of PGC-1α protein expression. The findings indicated that hydrogen gas inhalation could play the role as an effective antioxidant in response to the exercise, whilst it did not significantly affect mitochondrial biogenesis. The dose–response relationship and antioxidant effects in different types of exercise for hydrogen inhalation require further investigation.

Rising Canadian and falling Swedish radon gas exposure as a consequence of 20th to 21st century residential build practices

Radioactive radon gas inhalation is a major cause of lung cancer worldwide and is a consequence of the built environment. The average radon level of properties built in a given period (their ‘innate radon risk’) varies over time and by region, although the underlying reasons for these differences are unclear. To investigate this, we analyzed long term radon tests and buildings from 25,489 Canadian to 38,596 Swedish residential properties constructed after 1945. While Canadian and Swedish properties built from 1970 to 1980s are comparable (96–103 Bq/m3), innate radon risks subsequently diverge, rising in Canada and falling in Sweden such that Canadian houses built in the 2010–2020s have 467% greater radon (131 Bq/m3) versus Swedish equivalents (28 Bq/m3). These trends are consistent across distinct building types, and regional subdivisions. The introduction of energy efficiency measures (such as heat recovery ventilation) within each nation’s build codes are independent of radon fluctuations over time. Deep learning-based models forecast that (without intervention) the average Canadian residential radon level will increase to 176 Bq/m3 by 2050. Provisions in the 2010 Canada Build Code have not significantly reduced innate radon risks, highlighting the urgency of novel code interventions to achieve systemic radon reduction and cancer prevention in Canada.

Effect of Hydrogen Gas Inhalation on Patient QOL After Hepatectomy: Protocol for a Randomized Controlled Trial

Introduction: Molecular hydrogen had been considered inactive in vivo but is an antioxidant that selectively reduces highly toxic reactive oxygen species (ROS). Animal studies have reported that hydrogen gas inhalation helped alleviate cerebral and cardiac ischemia-reperfusion injuries. In humans, hydrogen inhalation therapy is presently approved as a treatment under Advanced Medical Care B in Japan (jRCTs031180352: limited to adult patients who suffered out-of-hospital cardiac arrest and are in a continuous coma) and its effectiveness is being examined in a clinical trial. The Japanese government has introduced the “Advanced Medical Care System” to promote the development of drugs and devices under governmental regulations. Advanced Medical Care B is a system designed for unapproved or off-label drugs or medical technologies used in a clinical trial setting. Hepatectomy is generally performed with repeated hepatic blood-flow occlusion and then reperfusion (ischemia and reperfusion). No report, however, has been made on ROS inhibition by hydrogen inhalation therapy or its effectiveness in post-hepatectomy patients. Hydrogen gas inhalation in the early stages after hepatectomy is anticipated to inhibit liver dysfunction by inhibiting ROS.Methods and analysis: This study is a randomized, controlled, double-blind trial which will be conducted as a “specified clinical trial” in accordance with the Clinical Trials Act in Japan. The subjects will be patients who will undergo hepatectomy and will be allocated randomly into group A with hydrogen gas inhalation or group B with air inhalation after hepatectomy. The study will examine if hydrogen gas inhalation improves QOL of post-hepatectomy patients. The primary endpoint is patient QOL (score of a 40-item quality of recovery questionnaire, QoR40) on postoperative day 3 and the secondary endpoints are QoR40s besides that on postoperative day 3, grade of postoperative complications (Clavien-Dindo score), level of pain (NRS: Numerical Rating Scale), amount of dietary intake, liver function, inflammation level, 8-hydroxydeoxyguanosine (urinary 8-OHdG) level, and number of pedometer-assessed steps.Ethics and dissemination: The protocol has been approved by the Niigata University Central Review Board of Clinical Research. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations.Trial registration number: jRCTs No. 03220332. Approved on 21 January 2021.

A case of multiple trauma and lighter gas inhalation

The rate of volatile substance abuse is increasing among young people around the world. A 10-year-old boy was brought to the emergency room by the 112-emergency ambulance service due to fall from the roof of a four-storey building. His general medical condition was moderate-poor; his GCS (Glasgow Coma Scale) was nine, blood pressure: 118/90 mmHg, heart rate: 98/min, O2 saturation was: 100%. Skin abrasions were present on his jaw and the occipital region of the scalp. The patient was accepted as a multiple trauma patient. When the patient's confusion did not resolve, the patient's father informed us that the child may have inhaled lighter gas. The patient was hospitalized at the pediatric ward and was discharged on the 14th day of admission as his symptoms completely improved. Clinicians should be alert with regard to acute and/or chronic end-organ damages in the cases of gas inhalation without any antidote.