Anti-inflammatory effect of pirfenidone compared to dexamethasone in ulcerative colitis model induced by acetic acid in rats: involvement of miR-146a and TLR4/NF-κB signaling.

Ulcerative colitis (UC) is a chronic autoimmune inflammatory condition distinguished by tissue damage in colonic mucosal layers. Several pro-inflammatory cytokines are involved in the immunopathogenesis of UC. Multiple studies showed that Toll-like receptor 4 (TLR4) expression markedly increases in UC patients. Thus, concentrating on this pathway may serve as the foundation for novel drug development targeting for treating or impeding the progression of UC. This study aims to explore the effects of pirfenidone (PRF) versus dexamethasone (DEX) on oxidative stress, tissue injury, inflammation, and fibrosis in a rat model of colitis using both biochemical and histopathological analysis. Colitis was induced by administering a single dose of 3% acetic acid (AA) intrarectally. Control animals received injections of an equivalent volume of 0.9% NaCl. Rats were then treated with either 14 days of DEX (2 mg/kg /day; p.o.) or PRF (100 mg/kg/day; p.o.). Animals were sacrificed on day 21 (7 days for acclimatization + 14 days for treatment), and then, the distal 10 cm of each colon was excised. Subsequently, all tissue samples were assessed for macroscopic damage, pathological findings, and different biochemical markers. Both drugs significantly suppressed the elevated levels of inflammatory markers, including TLR4, IL-1β, myeloid differentiation primary response protein 88 (MyD88), Bcl-2-associated X protein (BAX), nuclear factor kappa (NF-κB), tumor necrosis factor-alpha (TNF-α), microRNA-146a (miR-146a), caspase-3, transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), and myeloperoxidase (MPO), compared to the untreated UC Group. Additionally, they significantly elevated B-cell lymphoma 2 (BCL2) and platelet-derived growth factor (PDGF) levels, indicating their potential to mitigate inflammation and promote tissue repair. Histologically, PRF and DEX preserved intestinal structure as compared to the control group. PRF is considered a promising and effective anti-inflammatory alternative in the management of rat models of acetic acid-induced colitis.