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Hydrogen-an endogenous antioxidant in the body
... The tissue compatibility of hydrogen is satisfactory because it is an endogenous substance, which is continuously produced in the human intestine. 40 From the aspect of safety, hydrogen is advantageous to many other antioxidants as it shows no cytotoxicity even at high concentrations. Inhalation of hydrogen has already been used in the prevention of decompression sickness in divers and provided good safety profiles. ...
Hydrogen, one of the most well-known natural molecules, has been used in numerous medical applications owing to its ability to selectively neutralize cytotoxic reactive oxygen species and ameliorate hazardous inflammations. Hydrogen can exert protective effects on various reactive oxygen species-related diseases, including the transplantation-induced intestinal graft injury, chronic inflammation, ischemia-reperfusion injuries, and so on. Especially in the eye, hydrogen has been used to counteract multiple ocular pathologies in the ophthalmological models. Herein, the ophthalmological utilizations of hydrogen are systematically reviewed and the underlying mechanisms of hydrogen-induced beneficial effects are discussed. It is our hope that the protective effects of hydrogen, as evidenced by these pioneering studies, would enrich our pharmacological knowledge about this natural element and cast light into the discovery of a novel therapeutic strategy against ocular diseases.
... 33 Also, the tissue compatibility of hydrogen is greater than that of many other antioxidants because it is an endogenous substance. 35 Furthermore, hydrogen can also penetrate biomembranes and diffuse into the cytosol, mitochondria, and nuclei, thereby protecting nuclear DNA and mitochondria, suggesting that it could reduce the risk of lifestyle-related diseases and cancer. Last but not least, its relative concentration is quite high, and so it can react with low-density toxic ROS. ...
Hydrogen, a therapeutic medical gas, can exert antioxidant activity via selectively reducing cytotoxic reactive oxygen species such as hydroxyl radicals. Hydrogen-rich saline is an alternative form of molecular hydrogen that has been widely used in many studies, including metabolic syndrome, cerebral, hepatic, myocardial ischemia/reperfusion, and liver injuries with obstructive jaundice, with beneficial results. Osteoradionecrosis of the jaw is a serious complication following radiotherapy for head and neck cancers. It has long been known that most radiation-induced symptoms are caused by free radicals generated by radiolysis of H2O, and the hydroxyl radical is the most reactive of these. Reducing the hydroxyl radical can distinctly improve the protection of cells from radiation damage. We hypothesized that hydrogen-rich saline might be an effective and specific method of managing and preventing osteoradionecrosis of the jaw.
Magnesium alloy has a higher strength than the polymer, better toughness than ceramic materials, and the density, elastic modulus and mechanical properties are also closer to the body's natural bone. More importantly, magnesium alloy can be corrossed and degradated after implanted into the human body, neither cause side effects do not need the second surgery, so it was considered as a great potential biodegradable materials. However, excessive corrosion rate of magnesium in the body's physiological environment will lead to magnesium ions, hydrogen and corrosion sediment accumulation in the body, the local pH value increased and the mechanical structure was incomplete, reduce the treatment effect, and even cause adverse reactions and treatment failure. From the magnesium corrosion mechanism and degradation products in the human body impact were reviewed and analyzed the magnesium alloy in the future development direction and challenges.
Objective To study the protective effect of saturated hydrogen saline against cerebral ischemia-reperfusion injury and the related mechanism. Methods Rat middle cerebral artery occlusion (MCAO) models were established by thread ligation of the middle cerebral artery. The rats were sacrificed 24 h later. The cerebral infarction volume was determined by TTC staining, the water content in brain tissue by dry-wet weight method, the degree of cerebral cells by Nissl staining, and the levels of IL-1β and TNF-α in the ischemic cerebral tissues by ELISA. Results Compared with control group, hydrogen saline decreased the brain water content and cerebral infarction volume, and increased the quantity of nissel's body in the cortex; meanwhile, it also significantly decreased the concentrations of IL-1β and TNF-α in brain tissue(P<0. 05). Conclusion Hydrogen saline can alleviate the cerebral ischemia-reperfusion injury, probably by inhibiting the inflammation response.
Oxidative stress plays critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD), so therapy targeted on oxidative stress is of great importance for COPD. However, since the current used antioxidants are not satisfying, scientists have to find more effective antioxidants for COPD. Hydrogen, the most abundant chemical element in the universe, was recently discovered as a novel therapeutic medical gas, and has shown great antioxidant potential in a series of recent published researches for its feature of selectively reducing toxic reactive oxygen species. Based on these findings, we hypothesize that hydrogen gas therapy might be a novel, effective, safe, and economic treatment for COPD patients in one day.
The biological role of hydrogen molecule has been misunderstood in some cases. Recent studies have indicated that hydrogen molecule is a promising selective antioxidant and has prominent therapeutic effects on many disorders. This paper reviews the recent progress on medical application of hydrogen molecule and proposes the possible research directions.
Hydrogen sulfide (H(2)S) has been recognized as a toxic gas and environment pollutant. So, it is seldom regarded as a therapeutic gas. H(2)S has been recognized recently as a novel gaseous messenger and serves as an important neuromodulator in the central nervous system. Many researches have been focused on the protective role of H(2)S in treatment of several diseases. Like nitric oxide (NO) and carbon monoxide (CO), which are considered as two gaseous transmitters, H(2)S has been regarded as the third one. Recent studies provided evidence that H(2)S exerted antioxidant and anti-apoptotic effects, which protected neurons, cardiomyocytes, pancreatic β-cells and vascular smooth muscle cells against oxidative stress by scavenging reactive oxygen species (ROS) and reactive nitrogen species (RNS). It has been known that multiple factors, including oxidative stress, free radicals and neuronal nitric oxide syntheses as well as abnormal inflammatory responses are involved in the mechanism underlying the brain injury after acute CO poisoning. Studies have shown that free radical scavengers can display neuroprotective properties. Therefore, we hypothesize that H(2)S might be an interesting potential strategy for curing acute CO poisoning.
Hydrogen is a major component of interstellar space and the fuel that sustains the stars. However, it is seldom regarded as a therapeutic gas. A recent study provided evidence that hydrogen inhalation exerted antioxidant and anti-apoptotic effects and protected the brain against ischemia-reperfusion injury by selectively reducing hydroxyl radical and peroxynitrite. It has been known that the mechanisms underlying the brain injury after acute carbon monoxide poisoning are interwoven with multiple factors including oxidative stress, free radicals, and neuronal nitric oxide synthase as well as abnormal inflammatory responses. Studies have shown that free radical scavengers can improve the neural damage. Based on the findings abovementioned, we hypothesize that hydrogen therapy may be an effective, simple, economic and novel strategy in the treatment of acute carbon monoxide poisoning.
Hydrogen-oxidizing hydrogenase activity was detected in Helicobacter hepaticus and compared to the activity in Helicobacter pylori for characteristics associated with hydrogen uptake respiratory hydrogenases. Intact whole cells could couple H(2) oxidation to oxygen uptake, and no H(2) uptake was observed without oxygen available to complete the respiratory pathway. The H. hepaticus enzyme coupled H(2) oxidation to reduction of many positive potential acceptors, and it underwent anaerobic or reductive activation. H. hepaticus had a strong affinity for molecular H(2) (apparent K(m) of 2.5 micro M), and microelectrode measurements on the livers of live mice demonstrated that H(2) is available in the host tissue at levels 20-fold greater than the apparent whole-cell K(m) value.
Molecular hydrogen is produced as a fermentation by-product in the large intestine of animals and its production can be correlated with the digestibility of the carbohydrates consumed. Pathogenic Helicobacter species (Helicobacter pylori and H. hepaticus) have the ability to use H(2) through a respiratory hydrogenase, and it was demonstrated that the gas is present in the tissues colonized by these pathogens (the stomach and the liver respectively of live animals). Mutant strains of H. pylori unable to use H(2) are deficient in colonizing mice compared with the parent strain. On the basis of available annotated gene sequence information, the enteric pathogen Salmonella, like other enteric bacteria, contains three putative membrane-associated H(2)-using hydrogenase enzymes. From the analysis of gene-targeted mutants it is concluded that each of the three membrane-bound hydrogenases of Salmonella enterica serovar Typhimurium are coupled with an H(2)-oxidizing respiratory pathway. From microelectrode probe measurements on live mice, H(2) could be detected at approx. 50 muM levels within the tissues (liver and spleen), which are colonized by Salmonella. The half-saturation affinity of whole cells of these pathogens for H(2) is much less than this, so it is expected that the (H(2)-utilizing) hydrogenase enzymes be saturated with the reducing substrate in vivo. All three enteric NiFe hydrogenase enzymes contribute to virulence of the bacterium in a typhoid fever-mouse model, and the combined removal of all three hydrogenases resulted in a strain that is avirulent and (in contrast with the parent strain) one that is not able to pass the intestinal tract to invade liver or spleen tissue. It is proposed that H(2) utilization and specifically its oxidation, coupled with a respiratory pathway, is required for energy production to permit growth and maintain efficient virulence of a number of pathogenic bacteria during infection of animals. These would be expected to include the Campylobacter jejuni, a bacterium closely related to Helicobacter, as well as many enteric bacteria (Escherichia coli, Shigella and Yersinia species).
Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H(2)) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H(2) selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H(2) did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.
Carbohydrates are biomolecules abundantly available in nature. They are found in bewildering types ranging from simple sugars through oligo- and polysaccharides to glycoconjugates and saccharide complexes, each exhibiting characteristic bio-physiological and/or nutritional functions both in in vivo and in vitro systems. For example, their presence or inclusion in food dictates the texture (body) and gives desirable customer appeal (satisfaction), or their inclusion in the diet offers beneficial effects of great therapeutic value. Thus, carbohydrates are integrally involved in a multitude of biological functions such as regulation of the immune system, cellular signaling (communication), cell malignancy, antiinfection responses, host-pathogen interactions, etc. If starch is considered the major energy storage carbohydrate, the gums/mucilages and other non-starch carbohydrates are of structural significance. The most investigated properties of starch are its gelatinization and melting behavior, especially during food processing. This has led to the development of the food polymer science approach, which has enabled a new interpretive and experimental frame work for the study of the plasticizing influence of simple molecules such as water, sugars, etc. on food systems that are kinetically constrained. Starch, although considered fully digestible, has been challenged, and starch is found to be partly indigestible in the GI tract of humans. This fraction of starch-resisting digestion in vivo is known as resistant starch (RS). The latter, due to its excellent fermentative capacity in the gut, especially yielding butyric acid is considered a new tool for the creation of fiber-rich foods, which are of nutraceutical importance. By a careful control of the processing conditions the content of RS, a man-made fiber, can be increased to as high as 30%. Arabinoxylans are the major endospermic cell wall polysaccharides of cereals. In wheat they are found complexed with ferulic acid esters, which after oxidative coupling in vivo mediated by H2O2 and peroxidases or even by photochemical means give cross linked diferuloyl derivatives. The latter confer strength and extensibility to the cell wall and offer resistance for digestibility by ruminants. They also help blocking of the ingress of pathogens. The ester bound ferulic acid after oxidation in vivo generates reactive oxygen species that contribute to the fragmentation of non-starch polysaccharides (hemicelluloses), and thereby reduces the product viscosity, a property seen during long-term storage of rice. In plant tissues, the arabinogalactans are implicated in such diverse functions as cell-cell adhesion, nutrition of growing pollen tubes, response to microbial infections, and also as markers of identity expressed in the terminal sequences of saccharide chains.
Molecular hydrogen is produced in the large intestine of animals due to the fermentation reactions of sugar catabolism. The gastric pathogen Helicobacter pylori and the liver pathogen Helicobacter hepaticus have the capacity to use molecular hydrogen as a respiratory substrate. The amount of the gas within tissues colonized by these pathogens is ample, and use of H 2 significantly increases the stomach colonization ability of H. pylori. © 2003 Published by Éditions scientifiques et médicales Elsevier SAS.
We have recently showed that molecular hydrogen has great potential for selectively reducing cytotoxic reactive oxygen species, such as hydroxyl radicals, and that inhalation of hydrogen gas decreases cerebral infarction volume by reducing oxidative stress [I. Ohsawa, M. Ishikawa, K. Takahashi, M. Watanabe, K. Nishimaki, K. Yamagata, K.-I. Katsura, Y. Katayama, S. Asoh, S. Ohta, Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals, Nat. Med., 13 (2007) 688-694]. Here we show that the inhalation of hydrogen gas is applicable for hepatic injury caused by ischemia/reperfusion, using mice. The portal triad to the left lobe and the left middle lobe of the liver were completely occluded for 90min, followed by reperfusion for 180min. Inhalation of hydrogen gas (1-4%) during the last 190min suppressed hepatic cell death, and reduced levels of serum alanine aminotransferase and hepatic malondialdehyde. In contrast, helium gas showed no protective effect, suggesting that the protective effect by hydrogen gas is specific. Thus, we propose that inhalation of hydrogen gas is a widely applicable method to reduce oxidative stress.