title: Intestinal effects of nonselective and selective cyclooxygenase inhibitors in the rat.
abstract: It is now widely recognized that nonsteroidal anti-inflammatory drugs (NSAIDs) may cause extensive damage to the intestine. The pathogenesis of NSAID-induced intestinal injury, however, is still controversial and both local irritant actions and cyclooxygenase (COX) inhibition have been proposed as underlying mechanisms. In this study we investigated further on NSAID-induced intestinal damage by using nonselective (indomethacin and ibuprofen), COX-1 selective (SC-560) or COX-2 selective (celecoxib) inhibitors. NSAIDs were administered orally to conscious rats and small intestinal injury was evaluated 24 h afterwards in terms of macroscopic and microscopic alterations, myeloperoxidase activity, lipid peroxidation, number of enterobacteria in the mucosa and epithelial mucin content. Oral administration of indomethacin (20 mg/kg) induced macroscopic and microscopic damage to the small intestine, increased translocation of enterobacteria from lumen into the mucosa, myeloperoxidase activity and lipid peroxidation. Ibuprofen (120 mg/kg), SC-560 (20 mg/kg), celecoxib (60 mg/kg) or the combination of SC-560 plus celecoxib did not cause any intestinal injury nor modified the number of bacteria in mucosal homogenates. SC-560 significantly increased both myeloperoxidase activity and lipid peroxidation, whereas celecoxib significantly reduced myeloperoxidase levels, while leaving unaltered lipid peroxidation. Finally, all NSAIDs, mostly indomethacin, increased neutral mucins and decreased acidic mucins in the intestinal goblet cells. These results indicate that inhibition of cyclooxygenase, although variably influencing mucosal integrity homeostasis, is not sufficient to initiate acute intestinal damage in rats. Moreover, topical mucosal injury induced by the NSAID molecule seems to be a critical factor in the development of intestinal injury.
authors.affiliation: Department of Human Anatomy, Pharmacology and Forensic Medicine, University of Parma, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Menozzi
authors.forename: Cristina
authors.initials: C
authors.lastname: Pozzoli
authors.forename: Elena
authors.initials: E
authors.lastname: Giovannini
authors.forename: Elvira
authors.initials: E
authors.lastname: Solenghi
authors.forename: Daniela
authors.initials: D
authors.lastname: Grandi
authors.forename: Silvia
authors.initials: S
authors.lastname: Bonardi
authors.forename: Simone
authors.initials: S
authors.lastname: Bertini
authors.forename: Valentina
authors.initials: V
authors.lastname: Vasina
authors.forename: Gabriella
authors.initials: G
authors.lastname: Coruzzi
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D000068579:Celecoxib; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D004755:Enterobacteriaceae / Q000166:cytology / Q000254:growth & development; D007052:Ibuprofen / Q000008:administration & dosage / Q000633:toxicity; D007213:Indomethacin / Q000008:administration & dosage / Q000633:toxicity; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009077:Mucins / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D009077:Mucins; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; D009195:Peroxidase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D007052:Ibuprofen; D007213:Indomethacin