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

Abstract

(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.