The following articles are from Hydrogen Language
Dr. Shigeo Ohta, PhD, chief professor of the Institute of Geriatrics, Japan Medical University, whose research fields include molecular mechanism of hydrogen medicine, drug development of mitochondrial diseases and visualization and real-time monitoring of oxidative stress. In 2007, Professor Shigeo Ohta published a study on the alleviation of ischemia-reperfusion injury by a small amount of hydrogen in the international famous medical journal natural medicine, and proposed the concept of hydrogen selective oxidation resistance, which opened up a research boom of hydrogen medicine. It can be said that Professor Seiko OTA, has published more than 40 SCI papers in the field of hydrogen biomedicine, which confirmed the alleviating and therapeutic effects of hydrogen on cerebral ischemia, liver radiation injury, obesity and Parkinson's disease.
When I was exploring an ideal antioxidant without side effects, I came across hydrogen. In the first experiment in January 2005, I was surprised by the strong protective effect of hydrogen on oxidative stress and decided to devote my life to hydrogen medicine. In 2007, he successfully published his first paper in the Journal of natural medicine. When the first paper was accepted, we were surprised and confused with some questions, but we overcame them through constant publication. My mission is not only to develop hydrogen medicine, but also to develop the hydrogen industry and become the pioneer of hydrogen medicine. " （ http://www.molecularhydrogeninstitute.com/dr-shigeo-ohta-phd ）
Professor Seiko OTA has not only made outstanding achievements in the basic research field of hydrogen molecular biomedicine, but also actively cooperated with enterprises to promote the clinical application of hydrogen molecules. He has presided over the establishment of the first international hydrogen Medical Research Center (MHI) specializing in the biological effects of hydrogen molecules to promote the basic, animal and clinical research of hydrogen molecules
Professor Shigeo Ohta has been devoted to the study of oxidative stress injury for many years. In the field of hydrogen molecular action mechanism, he focused on exploring and discussing the mechanism of hydrogen biomedical action from the perspective of hydrogen molecule scavenging oxidation free radicals, regulating the function of plasma membrane channels and enhancing the activity of antioxidant system
1. Direct Reduction of Hydroxyl Radicals (· OH)
In the article published by Professor Shigeo Ohta in 2007, hydrogen can reduce • OH in cell experiments. More importantly, subsequent studies by others also confirmed that hydrogen rich eye drops can directly reduce • OH induced by retinal ischemia / reperfusion; In the testicular injury induced by ionizing irradiation, hydrogen molecules can also neutralize • OH. Although the reaction rate of • OH with H2 in dilute aqueous solution may be very slow, H2 cannot directly neutralize all • OH; However, mammalian cells have highly complex structures, including biofilms and viscous solutions with various concentrations. In the viscous environment, since the collision frequency is limited, the faster diffusion rate of H2 is conducive to overcoming the problem of slower reaction rate constant.
Because • OH is the main trigger of many free radical chain reactions, once this chain reaction occurs on the biofilm, it will continue and expand, causing serious damage to cells (Fig. 1). Hydrogen is more easily enriched in the lipid phase, especially in the unsaturated lipid region, which is the main target of the initial chain reaction. Therefore, hydrogen may have the effect of inhibiting the chain reaction of oxidation radicals. In the quantitative analysis, Professor Shigeo Ohta used liperfluoro and C11- BODIPY fluorescent to study the effect of H2 on peroxidation. The reaction domain of liperfluoro is hydrophobic and embedded in the plasma membrane. The reaction domain of c11-bodipy is hydrophilic and exposed in the cytoplasm. The reduction of c11-bodipy peroxidation induced by H2 was lower than that of liperfluoro, indicating that H2 inhibited the free radical reaction on the membrane. This chain reaction generates lipid peroxidation and leads to the production of markers of oxidative stress, such as 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA). A large number of experimental results show that sufficient H2 can effectively alleviate • OH induced tissue oxidation.
• OH can react indistinguishably with many target molecules and cause serious damage. Studies have shown that • OH can directly regulate the activity of Ca2+ channels. This inhibition of Ca2+ influx was completely eliminated by • OH scavenger. Another article also pointed out that • OH inhibits Ca2+ influx through L-type voltage dependent Ca2+ channels. Hydrogen molecules can clear • OH on the plasma membrane, which will inevitably affect the activity of Ca2+ channels.
In addition, mitochondrial adenosine triphosphate (ATP) sensitive potassium ion channel (MIT (ATP) K+ channel) is also regulated by • OH, which can sense and regulate the mitochondrial membrane potential of cell metabolism. Many studies have shown that some gases with physiological effects can participate in the regulation of the function of MIT (ATP) K+ channels and affect mitochondrial respiration and membrane potential. Focusing on the mechanism of action of physiological gases such as H2S, no and CO and MIT (ATP) K+ channels is of great significance for understanding the molecular function of H2.
2. Hydrogen Molecules Directly Reduce Peroxynitrite Anion (ONOO -) To Regulate Gene Expression
Another mechanism by which hydrogen molecules scavenge oxidation radicals is the direct scavenging of peroxynitrite anion (ONOO -). ONOO - is known to modify tyrosine in protein to generate nitrotyrosine. In animal models, nitrotyrosine content can be effectively reduced by introducing hydrogen rich water, injecting hydrogen rich saline or inhaling hydrogen. In addition, in clinical trials, drinking hydrogen rich water can reduce nitrotyrosine in patients with arthritis fluid. Therefore, at least part of the effect of hydrogen can be attributed to the reduction of nitrotyrosine production in proteins. Many protein factors involved in transcriptional control are nitrated (-O-NO2) or (-S-NO2). The reduced content of nitrated protein may affect the transcriptional regulation of many genes.
3. Indirectly Reduce Oxidative Stress By Regulating Gene Expression
Hydrogen molecules can upregulate the antioxidant system, including superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), etc. For nuclear factor 2-related factor (Nrf2), a transcription factor that can widely induce the expression of antioxidant enzymes, hydrogen molecules can upregulate its expression and activity, and indirectly up regulate the activity of the antioxidant enzyme system.
The upregulation of Nrf2 by hydrogen molecules is probably not caused by direct effects. Murakami. Proposed that H2 can activate mitochondrial activity. When excessive mitochondrial activity causes oxidative stress, H2 indirectly induces Nrf2 to transfer to the nucleus. However, no studies have shown how H2 activates mitochondria or whether oxidative stress of mitochondria is sufficient to activate nrf214.
In addition, some researchers also draw on the mechanism of mitochondrial coenzyme Q (mitoq). Mitoq is a mitochondrial targeting coenzyme Q derivative that can rapidly reach mitochondria as a mitochondrial targeting antioxidant. Mitoq significantly activated the keap1-nrf2 antioxidant system and increased the expression of Nrf2 target genes such as HO-1 and NQO1 genes15. Therefore, H2 may act as an antioxidant to activate Nrf2 in a mitoq like manner.
Another possibility is that the activation of Nrf2 is dependent on wnt/catenin signaling. Activated T nuclear factor (NFAT) inhibits the Wnt / catenin signaling pathway and is involved in regulating neural progenitor cell proliferation and differentiation, intestinal cell differentiation and osteoblast differentiation. On the other hand, wnt/catenin activates Nrf2. Therefore, when NFAT is cleared by H2, it may activate the wnt/catenin signaling pathway, causing the activation of Nrf2. However, the mechanism of hydrogen upregulating Nrf2 is still at the stage of exploration and speculation, and more experimental studies are needed.
