Rupatadine ameliorated ulcerative colitis in rats via modulation of platelet-activatiweng factor/interleukin-6/vascular endothelial growth factor signalling pathway

Abstract

Objectives: This study aimed to analyse the potential effect of rupatadine (RUP) on ulcerative colitis (UC) induced by acetic acid (AA).

Methods: Forty male adult Wistar rats were divided into five groups: Control group: received vehicles for 14 days; AA model group: received AA at the 13th day; Sulfasalazine (SLZ) + AA group: received SLZ (250 mg/kg) for 14 days and AA at the 13th day; RUP-3 + AA group: received RUP (3 mg/kg/day) for 14 days and AA at the 13th day; and RUP-6 + AA group: received RUP (6 mg/kg/day) for 14 days and AA at the 13th day. Evidence of UC was assessed both macroscopically and microscopically. Oxidative stress markers (total antioxidant capacity and malondialdehyde), antioxidant enzyme (superoxide dismutase), histamine and platelet-activating factor (PAF) were determined. Immunohistochemical estimations of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) were done.

Key findings: The AA group showed evidence of UC that was associated with a significant increase in oxidative stress, histamine and PAF levels with significant elevation in colonic VEGF and IL-6 immuno-expressions. RUP, in a dose-dependent manner, significantly ameliorated UC.

Conclusion: RUP protects against UC by reducing oxidative stress and by regulating the PAF/IL-6/VEGF pathway.

Keywords: histamine; interleukin-6; platelet-activating factor; rupatadine; ulcerative colitis.