Ionising Radiation Suppresses rAPC-Induced NLRP3 Expression and Associated Signaling in Rat Brain: Evidence for a Radiation-Sensitive Molecular Phenotype

Purpose: Recombinant activated protein C (rAPC) is widely regarded as an anti-inflammatory and cytoprotective agent; however, its molecular effects in the irradiated central nervous system remain poorly characterized. This study aims to characterize the gene expression profile triggered by rAPC in the rat brain and to evaluate how ionizing radiation alters these molecular (apoptotic and neuroinflammatory) responses.Material and Methods: Male Wistar Albino rats were randomly assigned to four experimental groups: untreated control, total body irradiation (9 Gy, TBI), rAPC (0.4 mg/kg, intravenous) alone, and TBI followed by rAPC. Brain tissue was collected for gene expression analysis of apoptosis, neuroinflammation, and oxidative stress-related markers.Results: Five genes showed significant omnibus effects. BAX expression (ε² = 0.62) was significantly reduced by both irradiation and rAPC alone; the combination group showed higher BAX than the irradiation-only group, suggesting partial restoration by rAPC. BCL-2 was reduced by irradiation and p53 was reduced by rAPC alone (η² = 0.38). Strikingly, rAPC alone selectively upregulated NLRP3 inflammasome expression (p = 0.023) with a consistent directional increase in TNF-α, a pro-inflammatory activation signature absent in irradiated groups. No significant changes were observed in oxidative stress markers, COX-2, FGFR, or CASP3. Conclusion: These findings reveal a radiation-sensitive molecular phenotype for rAPC in rat brain tissue. rAPC alone upregulates Nlrp3 expression and associated signaling while simultaneously reducing P53 and Bax expression, defining a multifaceted molecular profile that is substantially modified in the irradiated context.