免疫調節作用を有する新規化合物は亜全身照射による腸死を防ぐA novel immunomodulatory compound that prevents sub-total body irradiation-induced intestinal death

We have found that novel radioprotective agents, which are tentatively designated as compounds A and STA because a patent application is being considered, have remarkable protective effect against intestinal death in mouse sub-total body irradiation (SBI) experiments. In this study, we evaluated the radioprotective activity of a more effective compound, STA, in which one of the core structures of compound A is substituted to an ethyl group in order to enhance blood persistence and enhance the radioprotective effect. As a result, a potent radioprotective effect against radiation enteritis was observed in C57BL/6N mice treated with 26 Gy-SBI. The optimal dose of STA for the radiation protection was 10 mg/kg, while the maximum tolerated dose (MTD) is 40 mg/kg or less in a MTD study. Next, mRNA-Seq analysis of small intestinal mucosa was performed to identify genes related to radiation protection of acute gastrointestinal syndrome by STA. As a result, we found no significant change in any p53 target genes investigated and various changes of autoimmune or inflammatory response-related genes. Especially, many of the Toll-like receptor genes were down-regulated. In addition, SBI experiments were performed on Casp1/4(11)-deficient mice, which show a lack of producing inflammatory cytokines. STA did not show any radioprotective effect on the mice, indicating that the radioprotective effect of STA is dependent on Caspase-1/Caspase-4(11). Currently, we are confirming the reproducibility of the gene expression changes by STA using qPCR, and plan to report the results obtained.日本放射線影響学会第64回大