Suplatast tosilate reduces radiation-induced lung injury in mice through suppression of oxidative stress

Although radiotherapy is important in the treatment of malignant thoracic tumors, it has harmful effects on healthy tissues. We previously showed that suplatast tosilate, an anti-allergic agent, scavenged reactive oxygen species (ROS), including hydroxyl radicals. Because ROS-mediated oxidative stress is involved in radiation-induced lung injury, we hypothesized that suplatast tosilate could reduce radiation-induced lung injury via suppression of oxidative stress. Murine alveolar epithelial cells were irradiated with or without a medium containing suplatast tosilate in vitro to determine whether the agent had cytoprotective effects against radiation-induced injury. On the other hand, the thoracic region of C57BL/6 mice was exposed to a single irradiation dose of 15 Gy and the effects of suplatast tosilate were determined by a histological evaluation and assessment of the following parameters: cell number and inflammatory cytokine levels in bronchoalveolar lavage fluid, and oxidative stress markers and hydroxyproline content in pulmonary tissues. Suplatast tosilate protected murine alveolar epithelial cells in vitro from irradiation-induced inhibition of cell proliferation, which was accompanied by the suppression of intracellular ROS and DNA double-strand breaks induced by irradiation. Oxidative stress markers and the levels of inflammatory and fibrogenic cytokines were upregulated in irradiated murine lungs in vivo. Suplatast tosilate suppressed both oxidative stress markers and the levels of cytokines, which resulted in reduced pulmonary fibrosis and clearly improved the survival rate after irradiation. These findings demonstrate that suplatast tosilate could be a useful lung-protective agent that acts via suppression of oxidative stress associated with thoracic radiotherapy.