Egyptian Journal of Basic and Clinical Pharmacology

Egyptian Journal of Basic and Clinical Pharmacology
Vol. 3 (2013), Issue 2, pp. 21-29
doi:10.11131/2013/101345

Diazepam dose-dependently Aggravates Mucosal Damage in a Rat Model of Ulcerative Colitis

BACKGROUND: Psychiatric co-morbidities, such as anxiety, are common in patients with chronic gut disorders, including those with overt inflammatory conditions of the gastrointestinal tract. Among the available pharmacological options, anxiolytics such as benzodiazepines (BZDs) are considered to be effective drugs; however, no sufficient data are available about their direct effect on gut mucosal impairment. OBJECTIVES: The present work was designed to examine the effect of different doses of diazepam on a rat model of ulcerative colitis. METHODS: Three doses of diazepam were assessed comparatively in an experimental model of ulcerative colitis. Thirty six male albino rats were divided into 5 groups, each consisting of 6 animals; Group I: Sham operated group, Group II: ulcerative colitis was induced with 1 ml 5 % acetic acid by intracolonic instillation without treatment. Groups III, IV&V: diazepam 1, 3 or 6 mg/kg respectively, was administered i.p. for two days with and after inducing ulcerative colitis. Group VI: Vehicle treated group received polyethylene glycol i.p. Distal colon segment was evaluated both macroscopically and microscopically for the degree of damage. The inflammatory response was assessed by measurement of colonic myeloperoxidase activity (MPO), serum tumor necrosis factor (TNF)-α, as well as fecal lactoferrin and calprotectin levels. RESULTS: Rats with induced colitis showed macroscopic & microscopic signs of inflammation; this was associated with a significant increase in TNF-α, MPO as well as fecal lactoferrin and calprotectin contents. In a dose-dependent manner, diazepam administration, at the 3 dose levels, exacerbated the damage produced by acetic acid, this was revealed by gross inspection, as well as histologically and biochemically. CONCLUSIONS: Accordingly, the current study displayed that diazepam has deleterious effects when administrated to colitic rats.