Abstract
The most widely used cancer therapy is radiation therapy, but radiation damage to healthy tissues, particularly the gastrointestinal (GI) system, frequently reduces its effectiveness. This study investigates whether etoricoxib-loaded nanostructured lipid carriers (Et-NLC) could help shield the rat jejunum from radiation damage. Gamma irradiation (6 Gy) was used to damage the jejunum of Wistar albino rats, and then Et or Et-NLC (10 mg/kg b.w.) was administered orally for 14 days. It was found that the amounts of glutathione S-transferase (GST), superoxide dismutase (SOD), and nitric oxide (NO) decreased after irradiation but increased after Et-NLC therapy. Molecular analysis showed radiation-induced expression of microRNA-34a (miR34a), which may be involved in cellular stress response. Et-NLC treatments modulated the expression of miR34a, suggesting possible regulatory roles. Western blot analysis revealed changes in P53, interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2) levels. Et-NLC treatments decreased TNF-α, IL-6, IL-10, and COX-2 levels, indicating anti-inflammatory actions. DNA fragmentation analysis revealed a decrease in apoptotic activity after Et-NLC treatments. A histopathological examination confirmed that Et-NLC treatments had attenuated radiation damage, which had improved vascularization and reduced inflammation. The findings show that Et-NLC is more effective than Et-alone at reducing damage to the jejunum caused by radiation by controlling inflammation, oxidative stress, and apoptotic activity.