Molecular Hydrogen as an Antioxidant and Radioprotector: Mechanistic Insights from Monte Carlo Radiation-Chemical Simulations.

(1) Background: Water, comprising about 70-80% of cellular mass, is the most abundant constituent of living cells. Upon exposure to ionizing radiation, water undergoes radiolysis, generating a variety of reactive species, including free radicals and molecular products. Among these, hydroxyl radicals (•OH) are particularly damaging due to their very high reactivity and their capacity to induce oxidative injury to vital biomolecules such as DNA, membrane lipids, and proteins. From a radiation-chemical perspective, this study investigates the selective scavenging ability of molecular hydrogen (H2) toward •OH radicals, with the aim of evaluating its potential as an antioxidant and radioprotective agent; (2) Methods: We employed our Monte Carlo track chemistry simulation code, IONLYS-IRT, to model the time-dependent yields of ROS in a neutral, aerated aqueous environment. The simulations included varying concentrations of dissolved H2 and, for comparison, cystamine-a well-known sulfur-containing radioprotector and antioxidant. Irradiation was simulated using 300 MeV protons, chosen to mimic the radiolytic effects of low linear energy transfer (LET) radiation, such as that of 60Co γ-rays or fast (>1 MeV) electrons; (3) Results: Our simulations quantitatively demonstrated that H2 selectively scavenges •OH radicals. Nevertheless, its scavenging efficiency was consistently lower than that of cystamine, which produced a faster and more pronounced suppression of •OH due to its higher reactivity and superior radical-quenching capacity; (4) Conclusions: Molecular hydrogen offers several unique advantages, including low toxicity, high diffusivity, selective scavenging of •OH radicals, and well-documented anti-inflammatory effects. Although it is less potent than cystamine in terms of radical-scavenging efficiency, its excellent safety profile and biological compatibility position H2 as a promising radioprotector and antioxidant for therapeutic applications targeting radiation-induced oxidative stress and inflammation.