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INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Do Desipramine [10,11-Dihydro-5-[3-(methylamino) propyl]-5H-dibenz[b,f]azepine monohydrochloride] and Fluoxetine [N-Methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-propan-1-amine] Ameliorate the Extent of Colonic Damage Induced by Acetic Acid in Rats?

Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

The present study was designed to compare the anti-inflammatory and antioxidant effects of two antidepressant drugs, desipramine [10,11-dihydro-5-[3-(methylamino) propyl]-5H-dibenz-[b,f]azepine monohydrochloride] and fluoxetine [N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-propan-1-amine], administered with variable doses, on experimentally induced colitis in rats. Two doses for each drug (10 and 20 mg/kg/day i.p.) were injected in 48 adult male albino rats for 2 weeks after induction of colitis by intracolonic administration of 2 ml of 3% acetic acid. Several parameters, including macroscopic (ulcer score index) and biochemical such as myeloperoxidase (MPO), reduced glutathione (GSH), tumor necrosis factor (TNF)-, and interleukin (IL)-1β, were measured using standard assay procedures. The study demonstrates that both desipramine and fluoxetine significantly attenuated the extent and the severity of the macroscopic signs of cell damage. Both drugs significantly reduced tissue MPO activity in a dose-dependent manner. Both desipramine and fluoxetine, at either dose, significantly increased GSH in colonic tissue. Desipramine and fluoxetine, at either dose, significantly reduced TNF- and IL-β. Desipramine at the dose of 20 mg/kg produced more decrease in the level of TNF- compared with the effect of the smaller dose, but fluoxetine at 10 mg/kg diminished more in the level of IL-1β compared with the effect of the larger dose. The present data indicate that both desipramine and fluoxetine have anti-inflammatory and antioxidants effects in experimentally induced colitis in rats, opening the avenue to their possible protective role in patients with inflammatory bowel disease.

Address correspondence to: Dr. Nagwa Mahmoud Nour El Din, Department of Clinical Pharmacology, Alexandria Faculty of Medicine, 199 Port Said St., Sporting, Alexandria, Egypt. E-mail: kkatry{at}hotmail.com