Protective Effects of Oxytocin on Experimental Colitis: Modulation of Cytokines, Oxidative Stress, and Caspase-3 Activity

Background and Objectives: This study investigated the effects of oxytocin (OT) in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model in rats, focusing on its potential anti-inflammatory, antioxidant, and anti-apoptotic properties. Materials and Methods: Forty male Wistar albino rats were randomly assigned to five groups (n = 8): control (intrarectal saline), TNBS-induced colitis, dexamethasone-treated colitis (1 mg/kg, i.p.), and two OT-treated colitis groups (0.5 and 1 mg/kg, i.p.). Body weight changes were recorded over 72 h. Macroscopic and histopathological evaluations were performed following laparotomy and colectomy. Serum and colon tissue samples were analyzed for TNF-α, IL-1β, IL-6, MPO, MDA, GSH, GPx, SOD, and CAT levels. Immunohistochemical analysis of caspase-3 and oxytocin receptor (OTR), as well as immunofluorescence-based OTR expression, were assessed. Results: OT treatment significantly improved macroscopic and histopathological findings compared with the colitis group (p < 0.01). Tissue TNF-α and MDA levels were reduced, while antioxidant parameters were generally improved in OT-treated groups. Caspase-3 immunoreactivity decreased, indicating reduced apoptosis. Although some changes were observed in IL-6 levels, these were not consistent across all comparisons. OTR immunoreactivity appeared reduced in colitis and partially restored following OT administration. Conclusions: OT attenuates experimental colitis by modulating inflammation, oxidative stress, and apoptosis, and may contribute to mucosal healing. These findings suggest that OT has potential as a supportive therapeutic agent in inflammatory bowel disease; however, further studies are required to clarify its mechanisms of action.