Effect of electron beam irradiated-piroxicam on the anti-inflammatory activities in LPS-stimulated BMDC and sepsis-induced mouse models 2074

Abstract Description Piroxicam(Piro), a potent Non-steroidal anti-inflammatory drugs in the oxicam class, can cause significant gastrointestinal side effects. Ionizing radiation is an effective method for modifying molecules through radical reactions, which can reduce side effects, improve physical and chemical properties, and increase bioavailability. Therefore, in this study, we investigated the structural transformation potential of Piro through electron beam irradiation (IR) and evaluated the ability of IR-Piro to inhibit LPS-induced cellular inflammation and the inflammatory response in sepsis-induced mice. In BMDCs, we confirmed that neither unmodified Piro nor IR-Piro showed any cytotoxic effects at concentrations of 12.5 and 25 μM. In LPS-stimulated BMDCs, IR-Piro inhibited cytokines (TNF-α, IL-6, IL-12, IL-10) and reduced MHC-II expression as well as antigen presentation ability. The anti-inflammatory effects of IR-Piro were mediated by the suppression of COX-2 and PGE2. Notably, compounds extracted from IR-Piro showed greater inhibition than Piro. Intraperitoneal injection of Piro and IR-Piro in LPS-induced sepsis model mice decreased serum cytokine and chemokine levels. Although GOT and GPT levels increased with Piro treatment, no significant changes were observed with IR-Piro. Our findings indicate that IR-Piro offers strong anti-inflammatory benefits with reduced side effects, suggesting its promise as a new NSAID alternative. Funding Sources Supported by Korea Atomic Energy Research Institute Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)