Selenium nanoparticles ameliorate methotrexate-induced gastric fundus injury in adult male albino rats via TLR4/NF-κB signaling, apoptosis, and intercellular junctions modulation: biochemical and histological study

Despite its widespread application in the treatment of cancer and autoimmune diseases, methotrexate (MTX) is associated with several adverse effects. Selenium nanoparticles (SeNPs) have antioxidant and anti-inflammatory effects. This study aimed to investigate the ameliorating effects of SeNPs against MTX-induced gastric fundus damage and the possible underlying mechanisms. Rats were randomly allocated into five groups: control group, SeNPs group, MTX group, and two SeNPs administered groups either prophylactic or concomitant. Physical and macroscopic evaluations were performed. Gastric fundus specimens were collected for biochemical and histological changes. The Methotrexate group showed a significant decrease in weight gain, food intake, and gastric total antioxidant capacity (TAC). Also, there was a disruption of the gastric epithelial barrier indicated by the significant decrease in occludin, E-cadherin gastric levels, and zonula occludens-1 (ZO-1) immune-expression, together with mucous barrier alteration indicated by a significant decrease in Periodic acid-Schiff (PAS) stain mean area fraction. While gastric malondialdehyde (MDA), toll-like receptors 4 (TLR4), and Myeloid differentiation primary response 88 (MYD88) levels, the nuclear factor kappa B (NF-κB) and cleaved caspase 3 immune-expression were significantly increased. Furthermore, histological assessment revealed mucosal ulceration, vascular congestion, and inflammatory cellular infiltration with a significant increase in mast cells. Surprisingly, SeNPs administration attenuated oxidative stress, apoptosis, and TLR4/NF-κB signaling. Moreover, a significant increase in occludin, E-cadherin, and ZO-1 and a significant decrease in mast cell number were noticed with SeNPs administration together with histological structure preservation. Notably, the prophylactic treatment with SeNPs caused more improvement than its concomitant administration.