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Role of Molecular Hydrogen Inhalation Therapy on Muscle Dystrophy Molecular hydrogen, also known as hydrogen gas, has garnered attention in recent years for its potential health benefits, including its role in muscle dystrophy. In this blog post, we’ll explore what molecular hydrogen inhalation is, its potential benefits, and its role in muscle dystrophy. What is Molecular Hydrogen Inhalation? Molecular hydrogen is a gas that is naturally produced in small amounts by the human body. It can also be inhaled through the use of a hydrogen inhaler or hydrogen water. When inhaled, molecular hydrogen can enter the bloodstream and reach various tissues in the body. Benefits of Molecular Hydrogen Inhalation Preliminary research suggests that molecular hydrogen may have a number of potential health benefits. Some studies have found that molecular hydrogen may have anti-inflammatory and antioxidant effects, which may be beneficial for a variety of conditions. For example, molecular hydrogen has been shown to reduce inflammation in the gut, which may be helpful for people with inflammatory bowel disease. It has also been found to reduce inflammation in the brain, which may be beneficial for people with neurodegenerative conditions such as Parkinson’s disease. Molecular hydrogen has also been found to improve exercise performance, reduce fatigue, and reduce muscle damage after exercise. This may be due to its ability to reduce inflammation and oxidative stress, which can occur during exercise. Muscle dystrophy is a group of genetic conditions that cause muscle weakness and degeneration. There is currently not much cure for muscle dystrophy, and treatment is focused on managing symptoms and slowing the progression of the condition. Preliminary research suggests that molecular hydrogen may have potential benefits for people with muscle dystrophy. A small study published in the journal “Cell Reports Medicine” found that molecular hydrogen improved muscle strength and reduced inflammation in mice with a form of muscle dystrophy called Duchenne muscular dystrophy. Another study published in the journal “Free Radical Biology and Medicine” found that molecular hydrogen reduced muscle damage and improved muscle function in mice with a form of muscle dystrophy called Becker muscular dystrophy. However, it’s important to note that these studies were conducted in animal models and more research is needed to determine the potential benefits of molecular hydrogen inhalation in people with muscle dystrophy. What is Muscle Dystrophy Muscle dystrophy is a group of genetic conditions that cause muscle weakness and degeneration. It is caused by mutations in genes that are responsible for producing proteins needed for healthy muscle function. There are several different types of muscle dystrophy, including: Types of Muscle Dystrophy Duchenne muscular dystrophy: This is the most common and severe form of muscle dystrophy, affecting primarily boys. It typically develops in early childhood and progresses quickly, leading to severe muscle weakness and wasting. Becker muscular dystrophy: This form of muscle dystrophy is similar to Duchenne muscular dystrophy, but it is less severe and progresses more slowly. It can affect both males and females. Limb-girdle muscular dystrophy: This type of muscle dystrophy affects the muscles of the hips and shoulders, leading to weakness and difficulty with mobility. It can range in severity and can affect people of any age. Facioscapulohumeral muscular dystrophy: This form of muscle dystrophy affects the muscles of the face, shoulder blades, and upper arms. It typically develops in the teenage years and progresses slowly. Myotonic dystrophy: This type of muscle dystrophy affects the muscles and other organs, including the eyes, heart, and respiratory system. It is the most common form of adult-onset muscular dystrophy. Congenital muscular dystrophy: This is a genetic condition that is apparent between birth and 2 years old and causes muscle weakness and degeneration. Symptoms vary and may include poor motor control, inability to sit or stand without support, scoliosis, foot deformities, trouble swallowing, respiratory issues, vision problems, speech problems, and learning differences. Facioscapulohumeral muscular dystrophy: This is a genetic condition that affects the muscles in the face, shoulders, and upper arms. Symptoms may include difficulty chewing or swallowing, slanted shoulders, muscle weakness in the face, shoulders, and upper arms, and a distinctive facial appearance. Symptoms typically appear in the teenage years or early adulthood and can range from mild to severe. Side Effects of Muscle Dystrophy The side effects of muscle dystrophy can vary depending on the type and severity of the condition. Some common side effects may include: Muscle weakness and wasting Difficulty walking and mobility issues Scoliosis (curvature of the spine) Cardiac and respiratory problems Difficulty speaking, swallowing, and breathing Fatigue Pain Diagnosis of Muscle Dystrophy Muscle dystrophy is typically diagnosed based on a combination of the following: Medical history: A healthcare provider will ask about the patient’s symptoms and family medical history. Physical examination: A healthcare provider will examine the patient’s muscles and assess their strength and mobility. Laboratory tests: Blood tests may be done to check for genetic mutations associated with muscle dystrophy. Muscle biopsy: A small sample of muscle tissue may be removed and examined under a microscope to confirm a diagnosis of muscle dystrophy. Genetic testing: A blood test can be done to check for genetic mutations associated with muscle dystrophy. It’s important to note that muscle dystrophy is a complex condition and a definitive diagnosis may require a combination of these tests. Treatment for Muscle Dystrophy There is currently no cure for muscle dystrophy, and treatment is focused on managing symptoms and slowing the progression of the condition. Treatment options may include: Physical therapy: Physical therapy can help improve muscle strength and mobility, as well as reduce fatigue. Assistive devices: Devices such as braces, walkers, and wheelchairs can help improve mobility and independence. Medications: There are several medications that may be helpful in managing muscle dystrophy, including corticosteroids to reduce inflammation and slow muscle degeneration, and medications to improve breathing and heart function. Genetic counseling: Genetic counseling can help patients and families understand the genetic basis of muscle dystrophy and the risks of passing the condition on to children. It’s important to work closely with a healthcare provider to determine the best treatment plan for managing muscle dystrophy. Prognosis […]

Molecular Hydrogen And Its Importance As Medicine In Sports Sports is an activity comprising physical efforts and skills as the focus with the element of social involvement and competition. Concerning the health effects, sports is considered a double-edged sword. Positive health effects are attained through physical activity which is the key part of most sports. It also exerts some secondary effects that cause health benefits, for instance, personal development, psychosocial development, and less alcohol consumption. Sports bring a higher level of physical activity in the sportsman’s life and help to be aware of nutrition, exercise, and health [1]. Intense sports may cause muscular injuries and fatigue. Muscle damage or injuries are mostly attributed to an increase in exercise-induced oxidative stress that causes a decline in skeletal function. It is well known that exercise is the key element in sports to maintain physical strength. However, intensive endurance exercises can lead to an upsurge in oxygen consumption, production of reactive oxygen species (ROS), inflammation, ischemia-reperfusion injury, and white blood cell activation [2]. These physical exercise-related issues cause a decrease in sportsman’s performance and initiate other health problems. Considering all these factors, sports science needs an effective and easy-to-use medicine or therapeutic regimen to combat athletes’ health issues. Herein, molecular hydrogen is recommended because of its radical scavenging, and anti-inflammatory properties. This article will elucidate the importance of molecular hydrogen as medicine in sports. Here, we will start with learning about molecular hydrogen and its biological features. Molecular hydrogen Molecular hydrogen (H2) is a newly emerged treatment strategy that is found effective against several diseases and is also widely adopted by healthy people. Hydrogen, a therapeutic gas with no taste and odor offers several biological and therapeutic effects on numerous illnesses ranging from acute illness involving ischemia-reperfusion injury to chronic diseases namely neurodegenerative, rheumatoid arthritis, and metabolic diseases [3, 4]. Besides this, hydrogen is non-toxic and safe gas for therapeutic even at high concentrations. It quickly diffuses into tissues, crosses different tissue barriers i.e., the blood-brain barrier, and penetrates several organelles [5-7]. H2 also impedes reactive oxygen species (ROS) frequently produced in living systems, a characteristic that contributes to its antioxidant potential. Thus, it is recommended for the treatment of diseases linked to oxidative stress [8, 9]. Likewise, hydrogen is suggested as sports medicine because athletes or sportsmen deal with sports injuries i.e., muscle damage, often due to extensive oxidative stress and inflammation caused by intense exercises, and they opt for maintaining physical fitness. Molecular hydrogen is employed in therapeutics in different ways namely oral administration in form of hydrogen-rich water (HRW) or as hydrogen tablets, inhalation of hydrogen gas (HI), and injection as hydrogen-saturated saline. The concentration of hydrogen gas in tissues depends on the delivery route and the organ type after the exogenous supply [10]. We will mainly focus on the inhalation method for hydrogen gas use in sports. Molecular hydrogen as medicine in sports In the previous two decades, molecular hydrogen has evolved as an effective treatment regimen due to its anti-inflammatory, antioxidant, and anti-apoptotic effects illustrated in various animal disease models and human studies [11]. These characteristics make hydrogen therapy an attractive and promising agent in sports medicine. However, the significance of hydrogen gas utilization in sports is mainly attributed to its antioxidant effect. Because intensive and exhaustive physical exercise causes the overproduction of reactive oxygen species (ROS) and free radicals that facilitate tissue damage [12]. Therefore, using an effective antioxidant agent can help in diminishing oxidative and other cellular stresses. Moreover, it can relieve ROS-related disorders such as inflammation, fatigue, and micro-injury and thus help improve their fitness. Hydrogen gas therapy is suggested as an effective and innovative therapeutic strategy for sports injuries and exercise-induced oxidative stress with an adding potential for improving exercise performance in athletes [13]. Recent studies have also indicated molecular hydrogen as an alkalizing agent that can also affect cell signaling. Because of the identification of these recent mechanisms of action, the therapeutic application of molecular hydrogen has been extended in clinical medicine even further. In addition, hydrogen therapy trials for sports injuries are in progress and exhibiting favorable results [14]. We will summarize here the action mechanisms of hydrogen gas as sports medicine for eliminating harmful oxidative stress, inflammation, and resulting muscle injuries. Moreover, we are going to highlight its use in increasing overall athletes’ performance. Molecular hydrogen for exercise-induced oxidative stress Reactive oxygen species (ROS) are produced within the body as a result of the oxygen consumption through respiration in our daily lives [7]. These reactive molecules are eminent for performing a dual role as both detrimental and beneficial species. ROS plays a significant role in regulating cell homeostasis and molecular signaling under normal physiological circumstances [15]. Besides, exercise-induced excessive production of reactive oxygen species and decreased antioxidant defense systems play a crucial role in skeletal muscle contractile dysfunction that leads to fatigue and muscle weakness. Current studies continue to explore the underlying mechanisms through which oxidants affect skeletal muscle contractile characteristics while investigating therapeutic interventions capable of mitigating muscle damage induced via oxidative stress [12]. Considering this, hydrogen is suggested as the most promising candidate for athletes suffering from damaging oxidative stress due to its low molecular weight and high tissue penetrating ability to scavenge reactive oxygen species [8]. Also, H2 can diffuse quickly into tissue and scavenge toxic ROS because of its low molecular weight [8], making it a model candidate for athletes suffering from harmful oxidative stress. There are only limited studies that describe the potential of molecular hydrogen therapy in relieving exercise stimulated oxidative and cellular stress in in vivo and clinical settings. Thus, there is a dire need to explore the antioxidant capacity of hydrogen gas in sports-related health problems to validate its use as a medicine. Moving forward, oxidative stress is also associated with the production of inflammatory proteins as it regulates cell responses. Therefore, the anti-inflammatory role of hydrogen gas inhalation should be extensively evaluated to verify its use in the sports field. Hydrogen mitigates exercise-induced […]

Hydrogen Inhalation Therapy And Its Role In Lung Cancer    Introduction Oxygen, carbon monoxide, nitric oxide, hydrogen sulfide, and other gases make up gas signaling molecules (GSMs), which are essential for controlling signaling and maintaining cellular homeostasis. Interestingly, these compounds demonstrated the ability to treat cancer through a variety of administration routes. Hydrogen gas (molecular formula: H2) has recently come to light as yet another GSM with a range of biological properties, including anti-inflammatory, anti-ROS, and anti-cancer actions. Growing evidence indicates hydrogen’s potential for extensive and efficient application in clinical therapy, including the reduction of side effects associated with conventional chemotherapeutic medications as well as the inhibition of the growth of cancer cells and xenograft tumors (Li et al., 2019). Hydrogen as a novel therapeutic agent Every year, thousands of people would come to drink “holy water” from an abandoned mining pit in Germany, hoping to cure their illnesses. A group of kids suffering from leukemia was brought in to drink the holy water in 1986. After a few months, their symptoms started to significantly improve, and completed recovery was observed in one case. The high hydrogen content of the holy water was thought to be the reason for these improvements. However, survey data from 82 Chinese cancer patients published in 2019, presented the first evidence for “hydrogen oncology” (Chen et al., 2020). A number of studies have established the efficacy of hydrogen as a therapeutic agent. An experiment on mice with skin tumors, who inhaled a mixture of hydrogen (97.5%) and oxygen (2.5%), showed marked regression in the tumors (Dole et al., 1975). Hydrogen has been tested both in vivo and in vitro to prove its use as a safe and effective antioxidant (Ohsawa et al., 2007). Type 2 diabetes mellitus patients also benefited from drinking hydrogen water (Kajiyama et al., 2008). Hydrogen water supplementation decreases cholesterol and may have a preventive role in metabolic syndrome (Song et al., 2013). Hydrogen water improved UPDRS scores of patients with Parkinsonism in a study in Japan (Huang et al., 2018). An energy metabolic pathway flip from oxidative phosphorylation to aerobic glycolysis is linked to allergic airway inflammation. By flipping this switch back, hydrogen reduces inflammation of the airways in asthma and allergic airway inflammation (Niu et al., 2020) Hydrogen may also have implications in the treatment of gastric cancers (Zhu et al., 2021).                     Figure 1 Hydrogen therapy is a promising potential therapeutic option for a wide range of diseases (Figure 1). Gas inhalation as a disease therapy has recently gained popularity, and the list of therapeutic gases continues to expand. For unmet medical needs that currently place a heavy burden on people’s health, hydrogen has the potential to make a big difference as a unique and revolutionary treatment tool (Huang et al., 2010). Mechanism of Action of Hydrogen Eliminates reactive oxygen species (ROS) Several key factors in cancer, including ROS and antioxidant enzymes, are regulated by hydrogen. ROS are a group of oxygen-containing molecules that can harm DNA/RNA and proteins resulting in severe damage and apoptosis. External chemical attacks or an imbalance of regulatory systems result in excessive ROS production. During cancer, H2 inhalation selectively scavenges most cytotoxic ROS, such as hydroxyl radicals (OH) and proximities (ONOO), which play a causal role in tumor cell proliferation, invasion, and metastasis. By increasing the expression of antioxidant enzymes (SOD, HO-1, and Nrf2), hydrogen treatment enhances the elimination of ROS (Li et al., 2019) Modulates Inflammation Chemotherapy-induced inflammation in cancer patients leads to cancer spread and treatment failure in addition to causing serious adverse effects. Hydrogen can stop the growth and spread of tumors and lessen the negative effects of chemotherapy and radiotherapy by controlling inflammation. Tumor necrosis factors (TNFs), which are released by macrophages, and interleukins (ILs), which are released by leukocytes, are examples of typical inflammatory cytokines. Both have been linked to the development & spread of cancer, and hydrogen gas can block both ILs (especially IL-8, IL-1β) and TNFs (especially TNF-α) (Li et al., 2019). Enhances/Restores Mitochondrial Function During cancer, the mitochondria of T cells are destroyed. This loss of activity is due to the Inactivation of mitochondrial peroxisome proliferator-activated receptor γ coactivator 1α (PGC‑1α) (Kamphorst et al., 2017). H2 stimulates the gene expression of (PGC-1α) (Kamimura et al., 2016). Hydrogen can permeate into lymphocyte mitochondria as an antioxidant gas and selectively scavenge oxygen free radicals (Ohta, 2012). In 2019, Akagi and Baba observed an increase in T cells of cancer patients due to hydrogen inhalation. They further investigated whether the rise in T cell level was due to mitochondrial restoration. They were able to prove an increase in mitochondria of stage four lung cancer patients by using CoQ10 as a marker for mitochondrial restoration (Akagi and Baba, 2022). Boosts Immune System Aging of the immune system, chemotherapy itself, and other tumor-related factors are the main reasons for cancer recurrence and metastasis. Immune reconstitution with immune-enhancing drugs is carried out traditionally to avoid relapse after standard treatment. Hydrogen inhalation can be used for immune reconstitution. After 2 weeks of inhalation of a mixture of hydrogen and oxygen (66.7%: 33.3%) four hours per day; functional, cytotoxic, and helper T cells, NKT cells, Th1, natural killer cells, and Vδ2 cells increased in number while exhausted and senescent cytotoxic T cells decreased and restored back to the normal level (Chen et al., 2020). Genes and Signaling Pathways associated with Lung cancer Lung cancer accounts for 18% of all cancer-related deaths in the world (Sung et al., 2021). About 85% of lung cancers are non-small cell lung cancers (NSCLC) (Nawaz and Webster, 2016). Tobacco smoke is the cause of 85% of lung cancers. The smoke results in invasive and pre-invasive lesions, furthermore metastasis due to the gradual accumulation of irregularities in the genetic and epigenetic system. About one-fifth of the adenocarcinomas are not related to tobacco smoke at all. (Sun et al., 2007).            The carcinogens in tobacco smoke are significantly linked to the development of lung cancer and cause genetic changes by forming DNA adducts […]

Hydrogen Inhalation Therapy and Its Role as a Neuroprotective Agent Background: Neuro-inflammation is recognized in inducing neurology related problems, including those resulting from neurodegenerative-diseases, brain damage, and other diorders (Emerit, Edeas and Bricaire, 2004).  Neurological complications after surgery can range from a heavy stroke to a mild form of cognitive failure. Patients undergoing cardiac or vascular surgery, who are regarded to be at a higher risk for worse neurologic results, have been the focus of a large amount of work to improve outcomes. This effort has been focused on improving neurologic outcomes. Because there is a dearth of compelling clinical evidence, there are no established guidelines despite the fact that preclinical research has shown some encouraging results. The practice of neuroprotection can be classified into two primary categories: passive and active. Passive neuroprotection is defined as the avoidance of neurotoxic causes, whereas active neuroprotection involves the implementation of neuroprotective therapies. Neuro-protective medicines are drugs that can change the metabolic events following the beginning of the issues like ischemia, and so have the ability to minimize damage due to stroke. Not a single chemical medicine has demonstrated apparent beneficial effects among these therapies. Many of the agents like blockers of calcium channel and some antagonists have theoretical or experimental promise, but none has demonstrated clinical effectiveness.  Effectiveness of H2 at the Molecular Level: H2 is currently acknowledged as a gas with medicinal positive efficacy on several disorders, comprising neurological, metabolic, and inflammatory diseases. The neutral qualities of therapeutic H2 are believed to enhance the passive diffusion of H2 itself throughout the body soon after the supplying and to make sure a favorable safe profile as it is an inert gas and it does not disrupt any enzymatic processes in body. Hydrogen gas inhalation is now considered a basic medicinal technique. Hydrogen gas may be inbreathed by means of a cannula, facemask, or even a ventilation machine. Due to the quick action of hydrogen gas, it could be an ideal situation to combat stress caused by oxidation. Specifically, the inhalation of gas has no effect on blood-pressure (Ohsawa et al., 2007). In a study, group of scientists demonstrated that in approximately 20 minutes, the amount of hydrogen gas in blood of artery and veins achieved a plateau of 10–20 mM and had no effect on physiological markers, indicating no adverse consequences. Multiple pieces of evidence suggest that hydrogen lowers reactive oxygen species that are highly reactive in the area of chronic illness. Both inhaling H2 gas and injecting HS are capable of delivering detectable levels of H2 to the brain.  Mechanism of Action of H2 as a Potential Medicine: The precise chemical pathways behind the outcomes of lesser dose of hydrogen are still unknown. Multiple signal transduction pathways can be modulated by H2, although its basic molecular targets are unknown. Examining overlapped signaling molecules would aid in mapping cross-talk between important pathways. For a comprehensive explanation of roles of hydrogen gas in biological processes, and the molecular actions must be cleared. Proposed important mechanisms of action are shown in the illustration 1 below: Illustration 1. Potential mechanisms of Hydrogen gas at molecular level. (Ge et al., 2017) Using a specialized electrode, the diffusion of hydrogen gas within different tissues could be tracked. For instance, the H2 content within the rat myocardial has been measured. In order to assess the diffusion of hydrogen into ischemic myocardial region following coronary artery closure, the sensors were placed in the “at hazard” zone for an infarct.. Even with coronary artery closure, H2 content was elevated due to diffusion (Hayashida et al., 2008). Hydrogen Inhalation Against Ischemia  Ischemia poses a unique threat to the brain. It takes approximately 40 minutes of ischemia to destroy kidney or heart cells, yet just 5 minutes to kill susceptible neurons in numerous brain locations. The high metabolic rate of brain tissue contributes to its heightened susceptibility to ischemia injury. Although the human brain comprises just about 2.5 percent of the overall of body mass, it is responsible for 25 percent of metabolism, an energy expenditure that is three-and-a-half times that of other primate brains. Moreover, central neurons rely almost exclusively on glucose as an energy substrate, and brain glucose and glycogen stores are limited. In the past 15 years, however, evidence has accumulated suggesting that energetics considerations and energy substrate limitations are not the primary explanation of the brain’s increased sensitivity to ischemia. Under cerebral ischemia conditions, it appears that the innate cell-cell and subcellular signaling pathways of the brain, which are generally involved in information processing, become detrimental. This accelerates energy depletion and exacerbates the final steps that lead to ischemia cell death in all tissues. These pathways include free radical production, activation of enzymes for catabolism, breakdown of membranes, initiation of apoptosis, and the initiation of inflammation. Annually, around 7 hundred thousand Americans experience a stroke, of which 600,000 are first-time occurrences. (Benjamin et al., 2018). Significant progress has been achieved in treating strokes due to acute ischemia, which now involves medicinal recanalization of occluded artery (Furie and Jayaraman, 2018). Despite this, stroke remains a primary reason for fatality. An approximate of 7 million Americans aged 20 years or older have experienced an attack of ischemia (Benjamin et al., 2018). It has been shown that restoring blood flow does not terminate cellular harm. Despite the fact that neuroprotection studies on animal models of stroke have yielded promising outcomes, human therapies are unable to uncover any suitable molecule. Because of the complex nature of pathogenic reactions, cascades of apoptosis and cytotoxicity are unstoppable using a single molecule a single molecule. In addition, reduced distribution of the neuroprotective agent within the area of penumbra may diminish the impact. Therefore, a successful medicine must be readily accessible, diffuse swiftly, work on several linked pathogenic processes, and show minimal bad impacts on health. Interest in studying hydrogen’s neuroprotective effects has increased lately. In contrast to its effects on oxygen free radical, hydrogen peroxide, and nitric oxide, recent studies show that H2 preferentially […]

Hydrogen Inhalation Therapy and Its Role in Ovarian Cancer   Introduction: Worldwide, cancer is the leading cause of death, and its incidence continues to rise. There have been significant advances in basic and clinical cancer research over the past fifty years, resulting in a decline in mortality and incidence of certain cancers. Current cancer treatments, such as radiotherapy, chemotherapy, fine-needle aspiration, and surgery, can be a dual-edged sword as they can increase the number of circulating tumor cells and promote progression and spread of cancer (Neeman and Ben-Eliyahu, 2013, Karagiannis et al., 2017). Targeted precision therapeutic strategies based on molecular detection have not proven beneficial for the majority of cancer patients, with only 3-13% of patients having access to precision drugs.  According to many studies, precision therapy induces proteome secretion in high amount, resulting in cancer metastasis. Therefore, alternative cancer therapies are necessary to avoid these challenges. Since 2007, when Ohsawa and his colleagues published their startlingly effective therapeutic strategy results using molecular hydrogen on a rat model of cerebral infraction in Nature Medicine, it has been considered as a therapeutic and preventive medical gas. According to Ohsawa et al. hydrogen gas functions as a medicinal antioxidant by decreasing harmful oxygen radicals selectively. Acute oxidative stress generated by ischemia-reperfusion or inflammation produces severe tissue damage, and chronic oxidative stress is recognized as one of the major causes of prevalent diseases like, cancer (Ohsawa et al., 2007).  Advanced cancer treatment presents a serious challenge, demanding the development of novel concepts and methods. Molecular Hydrogen Basics: Hydrogen gas exhibits antioxidant and anti-inflammatory properties that may be utilized to combat cancer, the occurrence and advancement of which are closely linked to peroxidation and inflammation. The hydrogen gas is a moderate yet powerful antioxidant. It is the most abundant molecule in cosmos, comprising almost 75% of the universe’s mass. Hydrogen is a colorless, tasteless, and odorless diatomic gas with chemical formula H2 (Huang et al., 2010).  Hydrogen gas inhalation is a basic treatment approach. It can be inhaled using ventilator circuit, facemask, or nasal cannula to administer hydrogen gas. Since inhaled hydrogen has a quicker onset of action, it shows effective protection against acute oxidative stress (Ohta, 2011). Hydrogen Inhalation Role in Cancer Management: Hydrogen inhaled by patients with advanced cancer can improve the quality of life and inhibit cancer progression. As a technique for clinical rehabilitation of patients with advanced cancer, hydrogen inhalation is a simple, low cost treatment with few adverse effects that when inhaled the molecules get into lungs, and directly into bloodstream where they reach each and every cell quickly (Xu et al., 2019). Reactive oxygen species (ROS) are generated inside the body as a byproduct of oxidative phosphorylation in the energy metabolism of all aerobic organisms. When excessive ROS are created or endogenous antioxidant capacity is depleted, indiscriminate oxidation induces detrimental effects, leading to “oxidative stress”. A researcher explained in his work that OH free radicle is powerful enough to react with even inert H2, whereas O2.-, H2O2, and NO free radicles are insufficient to react with H2. In other words, hydrogen gas is mild enough to either interfere with metabolic redox processes or ROS involved in cellular signaling. (Ohta, 2014). Furthermore, it has been discovered that the biological and antioxidant benefits of H2 persists even after hydrogen gas has been eliminated from the body, especially at low concentrations, indicating that the process may have more to do with the modulation of antioxidant signaling than with the actual scavenging of free radicals (Dixon, Tang and Zhang, 2013). The nuclear translocation of nuclear factor erythroid-2 related factor 2 (Nrf2) may control the expression of genes involved in the oxidative stress management (Tonelli, Chio and Tuveson, 2018). H2 gas decreased inflammation in animal models induced by Concanavalin A (Kajiya et al., 2009), dextran sodium sulfate (Kajiya et al., 2009), and lipopolysaccharide (LPS) (Chen et al., 2013). H2 gas, H2-saline, H2-water reduced the levels of pro-inflammatory cytokines to minimize inflammation.  H2 has benefits against oxidative stress in addition to anti-inflammatory and anti-allergic properties. H2 regulates expression of several genes and phosphorylation of various proteins (Ohta, 2011). Despite numerous inaccuracies, selective free radical and inflammation scavenging ability are still widely acknowledged mechanism of H2. Pre-inhalation of H2 could prevent caerulein-induced acute pancreatitis in mice by reducing the early stage inflammation and oxidative stress, based on the evidence of a study (Li et al., 2021). In the adaptive immune system, Xi et al. study discovered comparable outcomes, which were primarily caused by a rise in the number of tired and senescent T cell subsets as well as a drop in the proportion of functioning subsets. Additionally, they discovered proof of T helper cell type 1 (Th1) and follicular Th cells’ limited capacity for cytokine release. They found that there was a decreased proportion of normal killer T cells (NKT), activated NK and killer NK cells, and an insufficient content of V2 subsets among T cells in the detection of innate immune response. As a result, it is very likely that both the innate and adaptive immune systems work in joint contribution to advance the cancer progression. Their study provides the first concrete proof that two weeks of hydrogen inhalation can considerably slow down the process pf aging as well as innate and adaptive immunity (Xu et al., 2020). Figure: Hydrogen’s ability to modulate the immune system. Immune homeostasis is upset when inflammation takes place because of dis-organized immune cells. By downregulating pro-inflammatory cells or upregulating anti-inflammatory cells, hydrogen intervention could reduce inflammation and restore the equilibrium. (Tian et al., 2021). Along with focusing on H2 neutralizing oxidative stress and immune response betterment, the mechanism prior to electron transport chain, which is the initial stage of mitochondrial oxidative stress, were also studied by researchers. Since they generate 90% of the cell’s energy in the form of ATP, mitochondria are frequently referred as the powerhouses of the cell. The production of ROS via forward and reverse electron transfer is accompanied by this mechanism, which depends […]

Molecular Hydrogen and its Role in Respiratory Diseases Introduction: Hydrogen, an inert gas, has been utilised to help deep divers prevent oxygen deprivation. (Gardette and Delauze, 1996). It was discovered in 2007 that inhaled hydrogen had genuine protection against brain damage caused by ischemia and reperfusion because of its anti-inflammatory and anti-apoptotic properties (Fukuda et al., 2007). This report generated tremendous interest internationally. The anti-oxidation (Ji et al., 2010), anti-inflammatory (Kajiya et al., 2009), anti-apoptotic (Cai et al., 2008) characteristics of H2 have been examined relative to its therapeutic impact on a variety of disorders. Hydrogen in its diatomic form is quite a small molecule that dissipates rapidly in whole body as well as all the cells, and its impact is quite week that it doesn’t interfere with redox events of metabolism or the pathways of cell signaling. As a consequence of this, it has the potential to be an effective and risk-free antioxidant for respiratory illnesses. Inhalation, which is by far the most common method of drug administration, is regarded as the most effective approach to treating asthma. Ischemic heart disease (Hayashida et al., 2008) stroke (Cui et al., 2016), acute lung damage (Kohama et al., 2015) and inflammatory bowel illness (Kajiya et al., 2009) have been shown to benefit from or be protected through the H2 gas inhaling approach, as data has accumulated in recent years.  The lungs are the major organ that are responsible for exchanging gases with the rest of the circulatory system and the surrounding environment. They are continuously being exposed to a variety of potentially harmful external stimuli, including bacteria, viruses, and other germs, cigarette smoke, and airborne particulate matter, as they are breathing in and out. Injuries to the lungs, including respiratory and lung disorders, are frequently the result of either short-term or prolonged contact to these hazardous compounds. Molecular Hydrogen- A Brief Introduction: Hydrogen molecules are odorless, tasteless, and colorless, and their solubility in water is quite low. In mammalian cells, under the conditions of physiological activity, it is regarded to be non-active. Certain types of bacteria are capable, through the process of enzymatic catalysis, of extracting energy and electrons from molecular hydrogen. In addition, the anaerobic metabolism of bacteria results in the production of molecular hydrogen. Genes that code for enzymes containing iron or nickel that are required to speed up processes. These enzymes are necessary (Fritsch, Lenz and Friedrich, 2013). Molecular hydrogen, on the other hand, has just come to be seen as a unique physiologically appropriate molecule with significantly important applications. A group of scientists found that the selective quenching of hydroxyl free radical (OH) and per-oxy-nitrite ion is brought about by inhaling of 1-4% molecular hydrogen. This results in a considerable improvement in injury caused by oxidative stress produced by different ischemia of cerebral areas of brain. (Fu and Zhang, 2022) Figure.1 Diagram depicting the potential biological consequences of hydrogen. Therapeutic Role of Molecular Hydrogen in Syndrome of Chronic Respiratory Dysfunction: Severe failure in gas exchange due to a breakdown in the alveolar-capillary barrier and pulmonary edema characterizes both acute lung injury (ALI) and its more severe variant, acute respiratory distress syndrome (ARDS). Both of these conditions can be fatal. During the past two decades, advances in intensive care have led to enhance the percentage of patients with ARDS who survive, although the death rate is still quite increased (Goss et al., 2003; Maybauer et al., 2006). Many medications with properties of anti-inflammation are investigated as potential treatments for ALI. Palrnatine is able to alleviate lipo-polysaccharide-induced ALI in lab mice and it does this via inhibiting activated AKT pathway of cell signaling (Kan et al., 2021). Recent research conducted on animal models in laboratories has suggested that hydrogen may have the ability to mitigate the disease spread of (ALI) brought on by any factor that may include sepsis or LPS or even some pathogenic effects.  A therapy with hydrogen can lessen the severity of inflammatory response in the tissues of lung, suppress NF-kB activation-mediated inflammatory response and cell death, ultimately it significantly attenuates the recruitment of neutrophil blood cells that is brought on by LPS. The lower expression of MPO activity in lungs and pro-inflammatory chemokines is the mechanism behind these protective benefits (Xie et al., 2012). The expression and activation of p38MAPK are both greatly suppressed by hydrogen (Liang et al., 2012), as are levels of ROS that are p38MAPK-dependent (Shi et al., 2016). Hydrogen’s therapeutic potential for ALI induced by LPS is promising, and it may be even more so when combined with NO. This is possible despite hydrogen’s good efficacy when used alone. Nitro tyrosine, which is generated by the inhalation of NO by itself, is removed when this gas is combined with hydrogen, suggesting that the mechanism may include the interplay between two gaseous entities (Liu et al., 2015). Hydrogen has the ability to attenuate the lung epithelial barrier dysfunction caused by LPS. Under typical circumstances, the alveolar epithelium functions as a substantial barrier that aids in the avoidance of edema of pulmonary regions.  Asthma and Molecular Hydrogen: More over 300 million individuals all over the world are afflicted with asthma, making it one of the most prevalent non-infectious chronic diseases. (Vos et al., 2012; Khalaf et al., 2019). Asthma is defined by a variety of immunological pathways, and (Papi et al., 2018) it is the result of complicated interactions between genes and the environment, and it can manifest itself in a variety ways clinically. The allergic response of inflammation caused type-II increase the defense mechanisms at the surfaces that contain mucosa are considered to be the underlying cause of asthma (Kubo, 2017). This sort of response of immunity continues producing cytokines type-II (Kubo, 2017; Kim et al., 2010), such as different types of interleukins, as well as the switching majority of the antibodies to immunoglobulin E (Pulendran and Artis, 2012). The chronic and complex lung illness known as asthma is connected with inflammation of the airways, which in turn causes heightened sensitivity, restricted airflow, and altered airway structure (Haahtela, 1997; Comhair et al., 2000). […]

Molecular hydrogen and its role in COVID-19 management Hydrogen gas has been used against many diseases and is considered a safe and reliable treatment with little or no adverse effects. In this article, we will explore the health benefits and action mechanisms of hydrogen gas in COVID-19 patients manifesting lung damage and other related complication. Molecular Hydrogen and Its Biological Effects Molecular hydrogen is the smallest inert gas, having no color, odor, or taste. Moreover, it is non-toxic and poorly soluble in water (1, 2). It is added as an essential constituent in the gas cylinders of deep-sea divers to help them breathe properly and prevent nitrogen decompression and illness (3). The therapeutic potential of hydrogen gas was first assessed by Dole et al. They studied that hyperbaric hydrogen could repress skin cancer in mice models after two weeks of treatment. However, later the application of hyperbaric hydrogen was restricted due to its transportation, storage and administration issues (4). Afterward in 2007, the use of low concentration of molecular hydrogen gas was proposed as a beneficial treatment in inflammation and ischemia/reperfusion animal models, considering its antioxidant and anti-inflammatory properties (5). Besides these, hydrogen also exerts anti-fatigue, anti-apoptosis, and regulatory effects. Molecular hydrogen can be administered in a number of ways i.e., hydrogen gas inhalation, hydrogen-rich saline and hydrogen-rich water (6). Hydrogen gas therapy has shown beneficial health effects in a variety of diseases, thus, it has also been proposed as a promising therapy for COVID-19 patients (7). In this article, we will explore the therapeutic potential of molecular hydrogen in the management of COVID-19 infection. However, before heading toward COVID-19 disease, let’s first understand the mechanism of hydrogen gas in ameliorating experimental lung damage and complications. Effects of Hydrogen gas inhalation on Experimental Lung Damage To understand the action mechanism of molecular hydrogen in lung damage improvement, several in vivo studies have been done. In these investigations, lung damage is introduced through experimental means to develop disease models. These models provide a convenient and reliable source for screening different treatment regimens. Different pathological processes such as acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) initiate in the lungs due to extreme, non-specific inflammation, which causes direct or indirect damage to lung tissues, including alveolar structures (8). Hydrogen gas has the ability to ameliorate lung damage effectively by using its antioxidant and anti-inflammatory characteristics. Such as hydrogen gas inhalation is reported to attenuate experimentally induced lung fibrosis by repressing oxidative stress and inflammation. Molecular hydrogen exerts these positive effects by inhibiting transforming growth factor (TGF-β1) and epithelial-to-mesenchymal transition (9). Similarly, hydrogen inhalation has proved to be an effective regimen against bleomycin-induced alveolar fibrosis that decreases respiratory physiological function. In this study, repeated hydrogen inhalation therapy was carried out for 21 days with 3.2% molecular hydrogen gas for six hours per day. The treatment increased ventilation and alveolar compliance which suggests it is a safe and effective therapy to ameliorate the clinical profile of patients with acute respiratory distress syndrome (10). Furthermore, safe concentrations of hydrogen gas can also mitigate ventilator induce lung damage in experimental mice models. It shows strong anti-inflammatory, anti-apoptotic and antioxidant effects in treating the condition. Mainly, hydrogen decreases ventilation-induced epithelial cell death by increasing the expression levels of anti-apoptotic genes. Additionally, adjunctive therapy with hydrogen gas inhalation is effective and appropriate for lung disease. Moreover, it is a straightforward and easily delivered therapeutic approach. (11). Moving forward, molecular hydrogen is found protective against hypoxia /re-oxygenation (H/R) injury to the lungs. It works by suppressing systemic and pulmonary inflammatory reactions and declining the production of hydroxyl radicals massively generated during H/R-induced lung damage (12). Like H/R, hemorrhagic shock and resuscitation (HSR) are known to initiate inflammatory responses in lung tissue causing acute lung injury and upsurging the risk of problems that can lead to death. Inhalation of hydrogen gas at 2% concentration is reported to minimize the rate of lung damage after HSR in a rat model. It reduces myeloperoxidase (MPO) activity, a pro-inflammatory molecule, and decreases the inflammatory cells’ infiltration to damaged lung tissue (13). These findings suggest that hydrogen gas has the ability to combat oxidative stress and inflammation, and regulate cellular machinery to exert a protective effect against lung tissue damage. Thus, it can also be a promising therapeutic option against the deadly coronavirus disease (COVID-19) and related lung injury and health complications.Considering these beneficial effects of hydrogen gas therapy in lung injury, we can suggest its use for combating COVID-19 infection. Role of molecular hydrogen in Coronavirus disease (COVID-19) management COVID-19 is a highly infectious and deadly disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus (2). It has exerted a disastrous effect on the world’s demographics and resulted in more than six million deaths worldwide, thus evolving as the most significant global health crisis (14). Most of the COVID-19 cases demonstrate a respiratory disease with unclear symptoms. It starts with a fever, fatigue, and dry cough and is trailed by shortness of breath (dyspnea) with the deteriorating disease. Among all patients, 80% may recover without any need for hospitalization, however, the rest 20% may develop pneumonia and severe acute respiratory distress syndrome (ARDS) (15). This indicates that the COVID-19 infection may range from silent to severe disease, involving death. The SARS-CoV-2 disease is also linked with the consolidation of the upper and lower lungs that causes respiratory breakdown along with hypoxia (lack of oxygen). Lung consolidation is meant by filling small airways in the lungs with water, blood, or pus rather than air (16, 17). Furthermore, fatigue, joint pain, headache, dyspnea, and lung, heart, and neurological damage are reported as long-term effects of coronavirus disease-19 (18). Oxidative stress and ROS production during COVID-19 infection Viral infections such as COVID-19 disease is associated with the infiltration of neutrophils and the production of reactive oxygen species (ROS). In addition to this, it also influences the antioxidant defenses of the body. Excessive ROS levels initiate a series of biological processes that lead to […]

Hydrogen Inhalation Therapy And Its Role In Cancer 1. Molecular Hydrogen Basics Molecular hydrogen is a small, colorless, tasteless, and odorless non-toxic gas with poor water solubility (1, 2). It is constituted in deep sea diver’s gas cylinders to help them breathe and avoid nitrogen sickness and decompression (3). An extensive research has been carried out past few decades on the benefits of hydrogen applications in a clinical setting featuring its anti-inflammatory, anti-oxidative, and anti-cancer properties (3, 4). Firstly, Dole et al explored the therapeutic potential of hydrogen gas in cancer. They reported that 2 weeks of hyperbaric hydrogen treatment caused significant repression of skin tumors in mice models (5). However, concerns regarding storage, transportation, and administration of hyperbaric hydrogen limited the use of this therapy. Nonetheless, a study conducted by Ohsawa et al in 2007 advocated that inhalation of small amounts of hydrogen gas could exert a neuroprotective effect by reducing oxygen radicals levels in ischemia-reperfusion or inflammation animal models (6). Since then, the promising therapeutic effects of molecular hydrogen have grasped an increasing attention. Several studies have examined the positive effects of hydrogen against inflammation, injury, metabolic syndromes, and cancer (7).         2. Hydrogen Role In Managing Treatment (Chemo And Radio) Side Effects Cancer is a heterogeneous and complex disease. It is a global health concern and the second major cause of mortalities in the world. Cancer management has been a complex process. Surgery, chemotherapy, and radiotherapy are the most widely opted treatment approaches for cancer (8). These treatment methods are linked with many adverse effects such as chemotherapy and radiotherapy cause oral mucositis, hepatotoxicity, hematopoietic system injury, gastrointestinal toxicity, nephrotoxicity, neurotoxicity, and cardiotoxicity in cancer patients. Nevertheless, these harmful impacts impede the clinical interventions of these conventional therapies in cancer management (9, 10). Additionally, they negatively affect the quality of life of a cancer patient and thus may lead to therapy discontinuation (11). Therefore, it is imperative to devise effective management approaches against radiotherapy and chemotherapy-stimulated side effects. Growing evidence has indicated that the molecular hydrogen gas can help relieve the adverse effects of conventional chemotherapy treatment. Moreover, it can also reduce the cancer cell growth and xenograft tumor, suggesting its prospective applications in clinical treatment (12, 13). Studies have shown that molecular hydrogen therapy can be combined with conventional cancer treatments i.e., surgical resection, radiotherapy, and chemotherapy, which often cause systemic inflammation, to reinstate normal tissue functioning (14).  Another study used hydrogen inhalation therapy in the radiation-stimulated dermatitis and skin injury mice model. The results indicated that the pre-inhalation of hydrogen gas can significantly decrease the severity of radiation-induced dermatitis conditions and also accelerate the wound healing process (15). A study evaluated the clinical safety and efficacy of hydrogen inhalation in patients with hearing impairment after chemotherapy/radiotherapy for nasopharyngeal cancer. The investigations revealed that hydrogen inhalation improved hearing in patients suggesting it as alternative rehabilitation therapy. Moreover, no other side effects such as vomiting, dizziness, nausea, chest pain, nosebleed, earache, and allergic reaction were observed after hydrogen inhalation (16). These studies infer hydrogen inhalation as a potent management strategy for combating radiotherapy and chemotherapy side effects and improving the quality of life in cancer patients. Considering this evidence, hydrogen inhalation therapy is currently being administered as an effective treatment approach against cancer. Moreover, it is also reported to be used as an adjuvant with chemotherapy and radiotherapy to combat their side effects and increase treatment effectiveness.                                                                                                                               3. Hydrogen Inhalation Role In Cancer Management Anti-cancer drugs are the most common therapeutic methods used for cancer treatment. However, many drugs have resulted in unsatisfactory therapeutic effects. Concerning this issue, hydrogen gas has not been reported to have any side effects like conventional anti-cancer drugs. Moreover, the hydrogen therapy is stated useful against many diseases triggered by chronic inflammation and oxidative stress (17). An effective anticancer treatment is laced with a proactive approach to killing cancer via deteriorating all its favorable surviving mechanisms. Here some basic mechanisms concerning hydrogen inhalation-mediated cancer management are discussed: a. Removal of Reactive Oxygen Species (ROS) Cancer is largely caused by mutations in nuclear and mitochondrial DNA. The mutations arise due to potent oxidizing reactive oxygen species (ROS) (17). ROS production increases in tumor cells as a result of gene mutation, upsurge in metabolic rate, and relative hypoxia. These reactive oxygen species are quenched by increased antioxidant enzymatic and non-enzymatic pathways of the cell. A moderate upsurge in ROS is responsible for many pathologic conditions such as tumor promotion and development. Furthermore, they are involved in the regulation of different cell signaling cascades. Additionally, ROS can initiate programmed cell death (18).  Molecular hydrogen possesses antioxidant properties. Studies showed that hydrogen gas inhalation could correct oxidative /antioxidative imbalance and exert an anti-tumor effect. Hydrogen selectively decreases oxidants of the harmful reactive oxygen species encompassing -OH (hydroxyl radicals) and ONOO- (peroxynitrite radicals) which cause tumor progression, cell invasion, metastasis, and cell proliferation. However, H2 does not interrupt metabolic oxidation-reduction reactions involved in cell signaling (19). Consequently, it is an effective antioxidant that can prevent cancer progression and development. b. Controls Inflammation Inflammatory cytokines are dysregulated in many diseases including cancer. They are a sequence of signal molecules that facilitate innate immune responses (20-22). They comprise tumor necrosis factors (TNFs) excreted by macrophages and interleukins (ILs) produced by white blood cells. Both of these are strongly involved in cancer onset and progression (12). Studies have shown that hydrogen gas can suppress both interleukins and tumor necrosis factors and help control inflammation (23, 24).  Furthermore, chemotherapeutic treatment in cancer patients induces inflammation that not only exerts severe harmful effects (25, 26) but also […]

Molecular Hydrogen and its role in Cardiovascular Diseases Cardiovascular diseases (CVDs) are one of the major health concerns worldwide. They contribute to most of the deaths, and the numbers are still upsurging (1). According to the world health organization report 2016, cardiovascular diseases are the leading reason of morbidity and mortality globally and were responsible for 17.9 million deaths, representing 31% of all worldwide casualties (2). Cardiovascular diseases are a group of medical conditions of the heart & blood vessels, such as coronary heart disease (CHD), heart failure, rheumatic heart disease, hypertensive heart disease, and stroke. Among heart diseases, stroke and ischemic heart disease are the leading cause of death and disability (3). Furthermore, coronary artery disease is another common heart ailment. It also contributes to deaths and disabilities at a massive level as well as accelerates the economic burden. It is estimated that around 23.3 million people may die of this disease by 2030 (4).  Considering these facts, the management of cardiovascular diseases is an exigent need of the global world. Several invasive and noninvasive treatment methods are available to relieve the disease symptoms; however, they are expensive and offer a wide range of side effects on patient health. Therefore, a low-cost, effective and safe treatment strategy is required to improve cardiac health and alleviate diseases. So here hydrogen inhalation therapy comes to light. This therapy has been extensively explored for its beneficial therapeutic effect against many human diseases, such as cancer and neurodegenerative diseases. However, several studies have shown its efficient use in the management of cardiovascular diseases that we will learn about in this article.                      Molecular hydrogen and its role in cardiovascular diseases Molecular hydrogen is an odorless, tasteless, colorless, and non-toxic gas having poor solubility in water. It is an inert molecule that does not react under optimum physiological conditions in mammals. Moreover, it is reported to exert a beneficial biological impact on almost all organs involving the lung, liver, brain, pancreas, and heart (5).  Molecular hydrogen represents an imperative molecule for alleviating reactive oxygen/ nitrogen species (ROS/RNS) regulated diseases and irradiation-induced diseases (6, 7). Besides this, hydrogen gas not only plays an effective part in the regulation of oxidative stress but also offers modulation of signaling pathways, and anti-apoptotic (cytoprotective) and anti-inflammatory effects (5, 8).  Cardiovascular diseases are contributed by many lifestyle and environmental factors. They are also triggered by oxidative stresses (9, 10), inflammation (11), and apoptosis (12) that can be effectively targeted via the therapeutic capacities of molecular hydrogen inhalation therapy.  To comprehend the cardioprotective effect of hydrogen gas, we need to learn the possible mechanisms behind its therapeutic potency against heart diseases. Mechanisms of molecular hydrogen action to relieve cardiovascular diseases Molecular hydrogen uses its anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms to relieve cardiac diseases and improve the overall health of the patients. These action mechanisms of hydrogen may work in synchronization to offer cardioprotective effects and improve cardiac morphology and function.   1. Reduction of reactive oxygen and nitrogen species (ROS/RNS) Oxidative stress is represented as an imbalance between reactive oxygen/nitrogen species and an antioxidant self-defense system in the body. This dyshomeostasis is considered as a potential cause of several pathological processes as it disturbs or damages imperative cellular and organ functions (13). Reactive oxygen species are generated from the reduction of oxygen that occurs during a typical cell metabolism activity. Reactive oxygen/nitrogen species may include free radicals i.e., OH, RO2, RO, nitric oxide, and other non-radical species which act as oxidizing molecules, for instance, peroxynitrite (ONOO-), ozone (O3), hydrogen peroxide (H2O2) (14). ROS are reported to regulate several gene signaling pathways that trigger cardiovascular pathophysiology. Moreover, peroxynitrite also plays a crucial part in the pathogenic mechanisms of certain heart conditions, including myocardial infarction, stroke, and chronic heart failure. Additionally, an acute or chronic unnecessary intracellular rise of reactive oxygen species is associated with the initiation and development of heart diseases as excessive ROS damage vascular and endothelial smooth muscle cell functions (15). Considering this, the antioxidant potential of molecular hydrogen grabbed massive attention and was investigated in view of cardiovascular diseases.  A study was carried out on chronic heart failure rat models to study the effect of hydrogen inhalation therapy. After one month of hydrogen therapy, the cardiac function was ameliorated in the treated group compared to the control. Further analysis showed that the molecular hydrogen significantly attenuated the apoptosis and oxidative damage in cardiomyocytes. This suggests hydrogen gas as an effective antioxidant with the potential to treat chronic heart failure disease (16). Similar to this another study explored that inhalation of low concentrations of molecular hydrogen suppresses oxidative stress, recurrent hypoxia-mediated dyslipidemia (imbalance of lipids due to low oxygen concentration in the tissues) and also precludes abnormal thickening and enlargement of heart muscles (cardiomyocytes hypertrophy) and perivascular fibrosis in the myocardium of left ventricle in a mice model. Thus, it is demonstrated that hydrogen inhalation plays a potent role in improving cardiac dysfunction (17).  Another recent study assessed the preemptive effect of hydrogen gas inhalation on vascular remodeling using a vascular injury mouse model. The study revealed that constitutive hydrogen gas inhalation partly diminishes vascular remodeling by removing reactive oxygen species and reducing oxidative stress. Therefore, hydrogen gas inhalation at safe concentrations is proposed as a safe and efficient approach to managing vascular diseases such as atherosclerosis, one of the major causes of myocardial infarction, stroke, and angina (18). Further, a study focused on hydrogen inhalation therapy for the improvement of ischemic heart disease and alleviation of ischemia/reperfusion injury. The investigations were carried out in a mouse model. Results showed that the therapy significantly decreased reactive oxygen species, and inflammatory signals mediated apoptosis and facilitated the alleviation of myocardial ischemia/reperfusion injury. Moreover, it also ameliorated the no-reflow phenomenon triggered by ischemia/reperfusion. Herein, the reflow phenomenon is the obstruction of blood flow to the ischemic area. It mainly occurs due to reperfusion therapy (19).  2. Anti-apoptotic effects Apoptosis is a […]

Role of Hydrogen Inhalation Therapy in Liver Diseases Liver is a vital organ inside your body. It aids your body in performing hundreds of tasks, including waste filtering, food digestion, energy storage, and toxin removal. Liver disease implies any medical condition that adversely affects the liver. These conditions may arise from multiple reasons; however they are attributed to liver damage and dysfunction. There are many types of liver diseases and some of these diseases are caused by viruses such as hepatitis. However, other diseases may occur due to excessive consumption of alcohol and drugs (1). Furthermore, long-lasting injury and scarring in liver tissue can lead to cirrhosis. In developed countries, alcoholic liver disease (ALD), hepatitis C virus (HCV), and non-alcoholic steatohepatitis (NASH) are the common causes of cirrhosis. Whereas, in the developing world, hepatitis B virus (HBV) and hepatitis C virus (HCV) are considered the main culprits (2). Globally, liver diseases are responsible for around 2 million deaths per year. Here, 1 million mortalities occur due to complications of cirrhosis, and the other 1 million happen due to hepatitis and hepatocellular carcinoma (HCC) or liver cancer (3). These facts indicate an undeniable burden of liver ailments in the world that need to be minimised by opting advance, cost-effective and wide-range therapeutic strategies. Currently, many treatment options are available and multiple liver infections and diseases are treated with medications, whereas some severe and end-stage patients may require surgery and liver transplantation. However, alcoholic liver disease, can be managed by reducing or stopping alcohol consumption, lifestyle improvements and losing weight, following a medical course and cautious observation of liver functions (4). Although, liver transplantation and other advanced treatment options have immensely helped in liver disease management. However, they are associated with many risks and complications, i.e., Ischemia-reperfusion injury (IRI), that can compromise the disease management and a patient’s well-being (5). Therefore, innovative, safe, and effective treatment options should be devised for liver illness treatment, such as molecular hydrogen. Molecular hydrogen and liver injury Molecular hydrogen is atomically the smallest gas that can readily diffuse through the body cells. Moreover, it is an inert gas and is present in trace amounts in the atmosphere (6, 7). Hydrogen therapy is gaining immense attention in the clinical setup. It has been reported as an effective treatment strategy for many kinds of diseases (8-11). These therapeutic abilities of molecular hydrogen are attributed to its high affinity, favourable characteristics, and inherent biosafety (12). Hydrogen therapy exerts its beneficial effects via multiple cellular mechanisms featuring its selective anti-inflammatory and antioxidant effects (13-16). Molecular hydrogen is administered in several ways to treat liver injury. It can be injected as hydrogen-rich saline, drunk as hydrogen-rich water and inhaled as hydrogen gas. Moreover, a bath of hydrogen-rich water and hydrogen-rich eye drops are also used as administration methods. However, the first three methods are frequently opted for the administration of molecular hydrogen in the case of liver ailments (12). Here, we will learn the therapeutic capacities of hydrogen gas against different liver problems via focusing hydrogen inhalation method. A few hydrogen therapy-treated liver diseases or problems are discussed below: 1. Liver ischemia/reperfusion injury Hepatic ischemia-reperfusion injury is one f the primary reason for liver transplant failure. It has become an imperative issue due to the rising scenario of liver transplantation regimens in liver diseases. Hepatic ischemia-reperfusion injury is divided into two distinct categories: warm and cold ischemia-reperfusion injury (IRI). Warm IRI occurs during the surgery when a transient fall in blood flow occurs to the liver. However, cold IRI happens during cold storage of the organ before the transplantation surgery. Both of these IRI types are linked with innate immune responses. Hepatic ischemia-reperfusion injury results in graft dysfunction and increased liver enzymes and biliary structures. Moreover, it increases the risk of acute and chronic transplant rejection and might cause early organ failure in 10% of cases (17). In addition, in some cases, IRI can cause systemic inflammatory response syndrome (SIRS) or multi-organ dysfunction syndrome (MODS) that accounts for high mortality and morbidity rates (18). Hydrogen inhalation therapy has been extensively used in improving liver ischemia-reperfusion injury. A study evaluated hydrogen inhalation therapy in an experimentally developed hepatic IRI mice model. They observed that inhalation of hydrogen gas at 1-4% concentration reduced liver cell death and decreased the serum levels of liver enzyme and hepatic malondialdehyde. Here, the hepatic malondialdehyde is an indicator or molecular marker of oxidative stress. Hydrogen gas showed a specific hepatoprotective effect and improved ischemia-reperfusion-mediated liver damage by suppressing oxidative stress (19). Like liver transplantation, liver tissue resection is another surgical procedure in which the damaged part of the liver is removed, and the rest of it regrows. This procedure is also associated with a hepatic ischemia-reperfusion injury that may cause liver failure and can be fatal. Research was carried out in pigs that underwent liver resection surgery. The animals were administered with hydrogen gas during general anaesthesia followed by interoperative preparations and warm ischemia, and reperfusion-induced liver injury. The liver tissue sections from IRI and non-IRI halves of the liver were then analyzed to evaluate the effects of inhaled hydrogen compared to the control (with no administration of hydrogen gas). The results showed that hydrogen gas undeniably suppressed the ischemia-reperfusion damage-related levels of oxidative stress. Thus the study suggests that hydrogen inhalation can exert protective effects against ischemia-reperfusion liver damage during tissue resection surgery (20). Another similar study was performed to evaluate the protective effect of molecular hydrogen gas in experimentally developed ischemia-reperfusion liver injury porcine models. The investigations revealed that the hydrogen gas showed a remarkable protective effect against ischemia-reperfusion injury in liver. Moreover, it was found safe and effective against the problem. All these attributes recommend molecular hydrogen use in clinical settings (21). Additionally, a study was conducted to examine the protective effect of hydrogen inhalation in pigs which underwent massive hepatectomy. Herein, hydrogen inhalation significantly attenuated the ischemia-reperfusion liver injury by decreasing oxidative stress and inflammation. These positive effects of hydrogen gas suggest it as […]