Protective Effect of Molecular Hydrogen Following Different Routes of Administration on D-Galactose-Induced Aging Mice.

Abstract

Using a D-galactose-induced aging mouse model, this study examined the effects of molecular hydrogen delivered via three distinct routes: 4% H2 inhalation, hydrogen-rich water ingestion, and hydrogen-rich saline injection. Plasma aging-related markers—including total antioxidant capacity, advanced glycation end products, tumor necrosis factor-α, free fatty acids, and alanine aminotransferase—showed improvement across all routes. In liver, brain, and heart tissues, malondialdehyde levels declined and superoxide dismutase activity increased, indicating reduced oxidative stress. Among the three routes, 4% H2 inhalation appeared to achieve the highest H2 uptake and showed superior efficacy on certain tissue-specific oxidative stress markers; however, the other two routes demonstrated comparable outcomes across most measured endpoints. These findings suggest that molecular hydrogen can suppress oxidative stress associated with D-galactose-induced aging regardless of the administration route employed.

Mechanism

Molecular hydrogen is proposed to directly scavenge reactive oxygen species, thereby reducing lipid peroxidation (MDA) and enhancing superoxide dismutase activity, while also suppressing TNF-α-mediated inflammatory signaling to attenuate oxidative stress-associated aging.