title: 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?
abstract: 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)-alpha, and interleukin (IL)-1beta, 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-alpha and IL-beta. Desipramine at the dose of 20 mg/kg produced more decrease in the level of TNF-alpha compared with the effect of the smaller dose, but fluoxetine at 10 mg/kg diminished more in the level of IL-1beta 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.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors.forename: Aida Ahmad
authors.initials: AA
authors.lastname: Guemei
authors.forename: Nagwa Mahmoud Nour
authors.initials: NM
authors.lastname: El Din
authors.forename: Azza Mohamed
authors.initials: AM
authors.lastname: Baraka
authors.forename: Inas
authors.initials: I
authors.lastname: El Said Darwish
mesh_terms: D019342:Acetic Acid / Q000009:adverse effects*; D000818:Animals; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003891:Desipramine / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology* / Q000627:therapeutic use; D005978:Glutathione / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D008297:Male; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D005473:Fluoxetine; D009195:Peroxidase; D005978:Glutathione; D019342:Acetic Acid; D003891:Desipramine