Molecular Hydrogen Protects against Various Tissue Injuries from Side Effects of Anticancer Drugs by Reducing Oxidative Stress and Inflammation.

While drug therapy plays a crucial role in cancer treatment, many anticancer drugs, particularly cytotoxic and molecular-targeted drugs, cause severe side effects, which often limit the dosage of these drugs. Efforts have been made to alleviate these side effects by developing derivatives, analogues, and liposome formulations of existing anticancer drugs and by combining anticancer drugs with substances that reduce side effects. However, these approaches have not been sufficiently effective in reducing side effects. Molecular hydrogen (H) has shown promise in this regard. It directly reduces reactive oxygen species, which have very strong oxidative capacity, and indirectly exerts antioxidant, anti-inflammatory, and anti-apoptotic effects by regulating gene expression. Its clinical application in various diseases has been expanded worldwide. Although H has been reported to reduce the side effects of anticancer drugs in animal studies and clinical trials, the underlying molecular mechanisms remain unclear. Our comprehensive literature review revealed that H protects against tissue injuries induced by cisplatin, oxaliplatin, doxorubicin, bleomycin, and gefitinib. The underlying mechanisms involve reductions in oxidative stress and inflammation. H itself exhibits anticancer activity. Therefore, the combination of H and anticancer drugs has the potential to reduce the side effects of anticancer drugs and enhance their anticancer activities. This is an exciting prospect for future cancer treatments.