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Inhalation of molecular hydrogen (H 2 ) gas ameliorates oxidative stress-induced acute injuries in the brain. Consumption of water nearly saturated with H 2  also prevents chronic neurodegenerative diseases including Parkinson’s disease in animal and clinical studies. However, the molecular mechanisms underlying the remarkable effect of a small amount of H 2  remain unclear. Here, we investigated the effect of H 2  on mitochondria in cultured human neuroblastoma SH-SY5Y cells. H 2  increased the mitochondrial membrane potential and the cellular ATP level, which were accompanied by a decrease in the reduced glutathione level and an increase in the superoxide level. Pretreatment with H 2  suppressed H 2 O 2 -induced cell death, whereas post-treatment did not. Increases in the expression of anti-oxidative enzymes underlying the Nrf2 pathway in H 2 -treated cells indicated that mild stress caused by H 2  induced increased resistance to exacerbated oxidative stress. We propose that H 2  functions both as a radical scavenger and a mitohormetic effector against oxidative stress in cells.

Molecular hydrogen protects against oxidative stress-induced SH-SY5Y neuroblastoma cell death through the process of mitohormesis