Optimization on the dose and time of nicaraven administration for mitigating the side effects of radiotherapy in a preclinical tumor-bearing mouse model

OBJECTIVE: Radiation-induced lung injury (RILI) is one of the serious complications of radiotherapy. We have recently demonstrated that nicaraven can effectively mitigate RILI in healthy mice. Here, we further tried to optimize the dose and time of nicaraven administration for alleviating the side effects of radiotherapy in tumor-bearing mice. METHODS AND RESULTS: A subcutaneous tumor model was established in the back of the chest in C57BL/6N mice by injecting Lewis lung cancer cells. Therapeutic thoracic irradiations were done, and placebo or different doses of nicaraven (20, 50, 100 mg/kg) were administrated intraperitoneally pre-irradiation (at almost 5–10 min before irradiation) or post-irradiation (within 5 min after irradiation). Mice that received radiotherapy and nicaraven were sacrificed on the 30th day, but control mice were sacrificed on the 15th day. Serum and lung tissues were collected for evaluation. Nicaraven significantly decreased the level of CCL8, but did not clearly change the levels of 8-OHdG, TGF-β, IL-1β, and IL-6 in serum. Besides these, nicaraven effectively decreased the levels of TGF-β, IL-1β, and SOD2 in the lungs, especially by post-irradiation administration with the dose of 20 mg/kg. Although there was no significant difference, the expression of SOD1, 53BP1, and caspase 3 was detected lower in the lungs of mice received nicaraven post-irradiation than that of pre-irradiation. CONCLUSION: According to our data, the administration of nicaraven at a relatively low dose soon after radiotherapy will be recommended for attenuating the side effects of radiotherapy.