Mechanisms of action of hydrogen

The ideal antioxidant is the one that mitigates the excess of oxidative stress without altering redox homeostasis. In other words, the ideal molecule must not reduce signaling molecules such as H2O2 but it must effectively reduce strong oxidants such as OH.

Since the hydrogen molecule is electronically neutral and much smaller than the oxygen one, it easily pass through cell and intracellular membranes. These are barriers which normally prevent water soluble antioxidants come into cells and organelles such as mitochondria, key source for ROS production.

Hydrogen selectively inactivates hydroxyl radicals (OH) by the means of water generation, but it does not react with O2- or with hydrogen peroxide H2O2. Hydrogen has shown to prevent DNA oxidation and to preserve the mitochondrial membrane potential as well as ATP synthesis in cell cultures, preserving cell morphology.

Hydrogen selective capability to neutralize hydroxyl radicals (OH) allows it to implement its cytoprotective effects in several ways.

  • First of all, hydrogen acts as a cell protector by reducing oxidative damage of DNA, lipids and proteins.
  • Furthermore, hydrogen (i) has an antiapoptotic effect; (ii) inhibits inflammatory mediators; (iii) increases endogenous antioxidant enzyme activity; (iv) downregulates activation of certain inflammatory signaling pathways; and (v) stimulates cell proliferation.

Recent studies have shown that the effects of hydrogen can not be attributed solely to the elimination of the OH radicals. It has been proposed that hydrogen improves the endogenous antioxidant activity as well, thus increasing the capability to neutralize free radicals and to modulate specific signalling pathways.