Oxytocin attenuates TNBS-induced colitis in rats by modulating inflammation, oxidative stress, and apoptosis

Current treatments for inflammatory bowel disease (IBD), such as ulcerative colitis, often involve immunosuppressants or biologics, which can have significant side effects and may not achieve sustained remission for all patients. There is a critical need for novel therapeutic strategies that can effectively manage chronic intestinal inflammation. Oxytocin, a neuropeptide primarily known for its roles in social bonding and parturition, has recently garnered interest for its potential anti-inflammatory and tissue-protective properties, making it a candidate for exploring in inflammatory conditions like colitis.

Researchers investigated oxytocin's effects in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model using 40 male Wistar albino rats, divided into five groups (n = 8 each). Colitis was induced intrarectally, and treatments included control (saline), TNBS-induced colitis, dexamethasone (1 mg/kg, i.p.), and two oxytocin groups (0.5 mg/kg, i.p. and 1 mg/kg, i.p.). Body weight changes were monitored over 72 h. Macroscopic and histopathological evaluations were performed post-colectomy. Serum and colon tissue were analyzed for inflammatory cytokines (TNF-α, IL-1β, IL-6), myeloperoxidase (MPO), oxidative stress markers (MDA, GSH, GPx, SOD, CAT), and caspase-3 and oxytocin receptor (OTR) expression via immunohistochemistry and immunofluorescence.

Oxytocin treatment significantly improved both macroscopic and histopathological findings in the colon compared to the colitis group (p < 0.01). This indicates a substantial reduction in disease severity. Tissue levels of the pro-inflammatory cytokine TNF-α and the oxidative stress marker MDA were reduced in oxytocin-treated groups. Conversely, antioxidant parameters, including GSH, GPx, SOD, and CAT, were generally improved, demonstrating enhanced cellular defense against oxidative damage. Caspase-3 immunoreactivity, a marker for apoptosis, decreased, suggesting oxytocin's anti-apoptotic effects. Although some changes were observed in IL-6 levels, these were not consistently significant across all comparisons. OTR immunoreactivity, which was reduced in colitis, showed partial restoration following oxytocin administration.

Oxytocin at both 0.5 and 1 mg/kg doses significantly attenuated experimental colitis, improving macroscopic and histopathological scores (p < 0.01) and reducing key inflammatory and oxidative stress markers.