Effect of roxithromycin on mucosal damage, oxidative stress and pro-inflammatory markers in experimental model of colitis.

ABSTRACT

OBJECTIVE AND DESIGN: Roxithromycin, a macrolide antibiotic, exhibits anti-inflammatory property. The present study was designed to evaluate its protective effect in a rat model of colitis. METHODS: The anti-inflammatory property of roxithromycin was first validated in rat paw edema model at 5 and 20 mg/kg doses where it produced 19 and 51% inhibition of paw swelling induced by carrageenan. The efficacy of roxithromycin was evaluated at these doses in a rat model where colitis was induced by intra-colonic instillation of acetic acid. Rats were divided into six groups viz. normal control, experimental control and drug-treated groups roxithromycin 5 and 20 mg/kg, diclofenac 10 mg/kg and mesalazine 300 mg/kg. All drugs were given orally 1 h before induction of colitis. The macro and microscopic changes, mean ulcer score, mucus content and markers of oxidative stress and inflammation were evaluated in all the groups after 24 h. RESULTS: Pretreatment with roxithromycin markedly decreased hyperemia, ulceration, edema and restored histological architecture. The protection afforded by roxithromycin was substantiated by dose-dependent increase in mucus content, normalization of markers of oxidative stress (GSH and TBARS) and levels of TNF-α, PGE2 and nitrite along with marked decrease in expression of NFκB (p65), IL-1ß and COX-2. The protective effect of roxithromycin was found to be comparable to mesalazine while diclofenac was found ineffective. CONCLUSION: Our study demonstrates that roxithromycin ameliorates experimental colitis by maintaining redox homeostasis, preserving mucosal integrity and downregulating NFκB-mediated pro-inflammatory signaling and suggests that it has a therapeutic potential in inflammatory conditions of the colon.