Hydrogen therapy as a potential therapeutic intervention in heart disease: from the past evidence to future application

Abstract

Cardiovascular disease is the leading cause of mortality worldwide. Excessive oxidative stress and inflammation play an important role in the development and progression of cardiovascular disease. Molecular hydrogen, a small colorless and odorless molecule, is considered harmless in daily life when its concentration is below 4% at room temperature. Owing to the small size of the hydrogen molecule, it can easily penetrate the cell membrane and can be metabolized without residue. Molecular hydrogen can be administered through inhalation, the drinking of hydrogen-rich water, injection with hydrogen-rich-saline, and bathing of an organ in a preservative solution. The utilization of molecular hydrogen has shown many benefits and can be effective for a wide range of purposes, from prevention to the treatment of diseases. It has been demonstrated that molecular hydrogen exerts antioxidant, anti-inflammatory, and antiapoptotic effects, leading to cardioprotective benefits. Nevertheless, the exact intracellular mechanisms of its action are still unclear. In this review, evidence of the potential benefits of hydrogen molecules obtained from in vitro, in vivo , and clinical investigations are comprehensively summarized and discussed with a focus on the cardiovascular aspects. The potential mechanisms involved in the protective effects of molecular hydrogen are also presented. These findings suggest that molecular hydrogen could be used as a novel treatment in various cardiovascular pathologies, including ischemic–reperfusion injury, cardiac injury from radiation, atherosclerosis, chemotherapy-induced cardiotoxicity, and cardiac hypertrophy.

Application of Electrolyzed Hydrogen Water for Management of Chronic Kidney Disease and Dialysis Treatment—Perspective View

“…H 2 has been demonstrated to possess anti-inflammatory, antioxidant, and anti-endoplasmic reticulum (ER) stress properties, and its involvement in the regulation of apoptosis, autophagy, and pyroptosis has been elucidated [12][13][14][15][16][17][18]. In this regard, H 2 can be considered a unique molecule that influences fundamental biological responses.…”

“…In this sense, excessive oxidative stress should be suppressed, but the degree of suppression should be at a level that does not compromise the benefits of reactive oxygen species to the body [15]. To date, while many preclinical studies using H 2 have confirmed organ-protective effects and correction of metabolic abnormalities through its antioxidant and anti-inflammatory effects [12][13][14][15][16][17][18], no severe side effects of H 2 loading have been observed. Therefore, the clinical application of antioxidant therapy with H 2 is considered a realistic challenge.…”

Therapies for Cirrhotic Cardiomyopathy: Current Perspectives and Future Possibilities

“…The small size of the hydrogen molecule allows it to easily penetrate the cell membrane to the cytosol. It is naturally metabolized without residue, and therefore, there are no side effects [ 75 ]. Similar to taurine and spermidine, hydrogen has antioxidant [ 76 ], anti-inflammatory, and anti-apoptotic effects [ 77 , 78 ].…”

Oxidative Mechanisms and Cardiovascular Abnormalities of Cirrhosis and Portal Hypertension

“…Because of the small size of the hydrogen molecule, it easily penetrates the cell membrane to the cytosol. Another advantage is that there are no side effects because it can be metabolized without residue [81]. Hydrogen exerts antioxidant [82], anti-inflammatory, and antiapoptotic effects [83,84], which has cardioprotective benefits.…”