Hydrogen Therapy in Cardiovascular and Metabolic Diseases: from Bench to Bedside.

A brief look at how the Inhalation of Hydrogen gas, attenuates / reduces Progression of Chronic Heart Failure via the Suppression of Oxidative Stress and regulating (gene expression) the P53 gene involved in premature cell death.

Background:

Continuous damage from oxidative stress or better known as free radical and apoptosis or cell death, are very important mechanisms that causes chronic heart failure (CHF). Molecular hydrogen (H2) with it's well proven effect as an extremely effective and targeted anti-oxidation. The objectives of this newsletter is to briefly illustrate the mechanism of H2 inhalation in delaying the progress of CHF. This newsletter is specifically focussed on CHF and Metabolic diseases, but is only one group of diseases that benefit from using Molecular Hydrogen in the co and mono-treatment of these diseases.

What is Molecular Hydrogen and why uses it as a medical gas:

Hydrogen (H2) is colorless, odorless, and the lightest of gas molecules. Studies in the past ten years have proven that H2 is extremely important in regulating the homeostasis of the cardiovascular system and metabolic activity. Delivery of H2 by various strategies improves cardiometabolic diseases, including atherosclerosis, vascular injury, ischemic or hypertrophic ventricular remodeling, intermittent hypoxia- or heart transplantation-induced heart injury,

obesity and diabetes in animal models or in clinical trials.

The purpose of this newsletter is to summarize the physical and chemical properties of H2, and then, the functions of H2 with an emphasis on the therapeutic potential and molecular mechanisms involved in the diseases above. We hope this review will provide the future outlook of H2-based therapies for cardiometabolic disease.

Hydrogen (H2), is a natural part of normal biological processes in humankind and is produced by intestinal bacteria in mammals.The earth?s atmosphere contains less than 1 part per million (ppm) of H2 H2 is a highly combustible diatomic gas when it is present with a specific catalyst or in the presence of heat. H2 is flammable only at temperatures higher than 527 °C. H2 can be dissolved in approximately 0.8mM (1.6 ppm, wt/vol) of water at one atmospheric pressure.

Endogenous or internally produced H2 is catalyzed and produced by hydrogenases (H2ases) in bacteria, such as Escherichia coli, Bacteroidetes and Firmicutes in colon. The great majority of H2ases

contain iron-sulfur clusters and two metal atoms at their active center. These and other enzymes that assist with catalysing the reversible oxidation of H2 (H2 ? 2 H+ + 2 e-) and play a central role in microbial energy metabolism.

However, mammalian cells have no functional hydrogenase genes. In mammalian cells, H2 is proven to cross the blood brain barrier, it has the ability to penetrate membranes and diffuse into organelles, such as mitochondria and nucleus. In 2007, Ohsawa et al [10]. reported that H2 is able to react with cytotoxic oxygen radicals by reacting with the hydroxyl radical (?OH), but not ?O2 -, H2O2 and NO in cultured cells. Due to its ability to inhibit oxidative stress, inflammation, and apoptosis, H2 is emerging as a fourth gaseous signaling molecule (NO, carbon monoxide, hydrogen sulfide, and H2) within the body.

During the past ten years, benchtop and clinical research and trials, has proven that H2 is an important pathophysiological regulatory factor with very potent anti-oxidative, anti-inflammatory and anti-apoptotic effects on cells and organs. Delivery of H2 by inhalation or injection with H2, injection with H2-rich saline drinking H2-rich water, has been proven to protect against cardiovascular and metabolic diseases, such as atherosclerosis, glucose and lipid metabolism disorder, myocardial ischemia/reperfusion (I/R) injury, myocardial transplantation injury, or cardiovascular hypertrophy.As discussed previously in our newsletters.

Conclusion and finding

As a safe antioxidant, anti-inflammatory, gene modulator and inhibitor of apoptosis, molecular hydrogen uniquely and safely, mitigates the progression of CHF via inhibiting apoptosis modulated by p53. Therefore, H2 is clearly indicated as a potent therapeutic application in protecting CHF in the future.

Various studies and clinical trials has revealed that molecular hydrogen markedly reduce oxidative stress and suppress myocardium injury in vivo and in vitro. Inhalation of H2 prevents CHF from progressing and protect the cardiac function by reducing apoptosis of cardiomyocyte. Meanwhile, H2 has also be confirmed as protecting cardiomyocytes from oxidative stress-induced apoptosis. Notably, the expression and phosphorylation of p53 play an important role in CHF when treated with hydrogen.

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