P-24 Racanisodamine attenuates radiation-induced lung injury by activating the NRF2 pathway: In vivo studies

Racanisodamine, also known as 654-2, is an alkaloid extracted from the Solanaceae plant Scopolia tangutica in China. It a toxic mushroom-type M receptor antagonist. Racanisodamine used to treat diseases such organophosphorus poisoning, septic shock, pulmonary valve stenosis, and gastric ulcers. Additionally, can alleviate oxidative stress, inflammation, cell apoptosis induced by bleomycin-induced acute lung injury mice. inhibit inflammation lipopolysaccharide (LPS) rat model. has protective effect on kidney propylene glycol LPS, rhabdomyolysis. However, there currently no research of radiation-induced (RILI) its mechanism.This study explores whether therapeutic RILI using mouse model, providing new theories methods for clinical treatment RILI. C57BL/6 mice were randomly divided into four groups: control, control+Racanisodamine, 18 Gy irradiation (model), combined with irradiation. The +18 group intraperitoneally injected (5mg/kg) three days before throughout experiment. Single chest was performed model Racanisodamine+model groups. control+Racanisodamine model+Racanisodamine groups once day until 6 weeks after Lung histopathology observed HE staining, while fibrosis assessed Masson staining. Serum bronchoalveolar lavage fluid inflammatory cytokines, TNF-α, IL-1β, IL-6, determined ELISA. Cell senescence detected SA-β-Gal expression γH2A.X, NRF2, p-NRF2, p62 tissue immunofluorescence, immunohistochemistry, western blot. Compared group, exhibited significantly alleviated (t=8.660, 9.859, P < 0.01). levels IL-6 reduced (t=8.17、4.583、6.541, DNA damage (t=17.41, 0.01) group. NRF2 p-NRF2 enhanced (t=4.896, 5.623, plays role alleviating mitigating fibrosis, reversing caused may be associated activation NRF2-related pathway.