Mitigative effects of Otilonium Bromide on methotrexate-induced hepatic damage in rats

OBJECTIVE: Hepatotoxicity is a significant adverse effect associated with long-term methotrexate (MTX) treatment, limiting its clinical utility. This study aimed to comprehensively evaluate the potential hepatoprotective effects of Otilonium Bromide (OB) against MTX-induced liver injury in an experimental rat model by integrating biochemical, molecular, and histopathological assessments. RESULTS: MTX administration resulted in significant structural and functional liver damage, as evidenced by elevated biochemical markers, alanine aminotransferase (ALT), transforming growth factor-beta (TGF-β), NOD-like receptor family pyrin domain-containing 3 (NLRP3), platelet-derived growth factor (PDGF), malondialdehyde (MDA) and worsened histopathological scores, including increased hepatocyte necrosis, fibrosis, and cellular infiltration. Treatment with OB significantly reduced these biochemical markers and improved histopathological changes compared to the MTX + saline group. Otilonium Bromide demonstrated hepatoprotective effects in the rat model of MTX-induced liver injury, likely through its anti-inflammatory and antifibrotic properties. These effects may be mediated by modulation of oxidative stress and the intestinal microbiome. Further studies are needed to explore its clinical applicability.