Differential salutary effects of nonselective and selective COX-2 inhibitors in postoperative ileus in rats
| Autor: | Marek Ujda, Jacek Petrusewicz, R. Korolkiewicz, Jarosław Ruczyński, Piotr Rekowski, Jarosław Dąbkowski |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Arginine medicine.medical_treatment Nitric Oxide Synthase Type II Nitric Oxide Nitric oxide chemistry.chemical_compound Postoperative Complications Laparotomy Internal medicine medicine Animals Cyclooxygenase Inhibitors Enzyme Inhibitors Rats Wistar Evans Blue Cyclooxygenase 2 Inhibitors biology business.industry Lysine Intestinal Pseudo-Obstruction Small intestine Rats Intestines Isoenzymes Nitric oxide synthase NG-Nitroarginine Methyl Ester Endocrinology medicine.anatomical_structure chemistry Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Models Animal Prostaglandins biology.protein Surgery Cyclooxygenase Nitric Oxide Synthase Gastrointestinal Motility business Nimesulide medicine.drug |
| Zdroj: | Journal of Surgical Research. 109:161-169 |
| ISSN: | 0022-4804 |
| DOI: | 10.1016/s0022-4804(02)00095-1 |
| Popis: | Background. Postoperative ileus (PI) is a common surgical complication, the treatment of which consists of supportive measures. Aim. The effects of several cyclooxygenase (COX) inhibitors and their interaction with l -arginine/nitric oxide synthase (NOS) pathway were tested in a rat PI model. Methods. Intestinal transit was measured as Evans blue migration after skin incision, laparotomy, or laparotomy followed by evisceration and gut handling. Results. In contrast to a selective inducible NOS (iNOS) blocker, l -N6-(1-iminoethyl)lysine hydrochloride (L-NIL), Nω-nitro- l -arginine methyl ester (L-NAME) reversed the additional inhibitory effects of gut manipulation after laparotomy on the gastrointestinal transit (GI) in a dose-dependent, l -arginine-sensitive manner. Laparotomy and manipulations of small intestine increased blood plasma nitrites and nitrates level (NOx), an effect preventable by L-NAME. Indomethacin, resveratrol (selective COX-1 blocker), and COX-2 antagonists, nimesulide, NS-398, DuP-697, and L-752860, attenuated the additional inhibitory effects of gut manipulation following laparotomy in a dose-dependent manner. In contrast, only nimesulide, NS-398, DuP-697, and L-752860 partly, but significantly, reversed the effects of laparotomy on the intestinal transit. Administration of L-NAME subsequent to COX inhibitors abolished the salutary effects of the latter, implying that at least the synthesis of either NO or prostanoids must remain unaffected to enable a return of GI transit during the postoperative period. Conclusion. In addition to NO synthesized by constitutive NOS (cNOS), prostaglandins produced by both COX-1 and COX-2 participate in the pathogenesis of PI, albeit in different pathological mechanisms. Thus laparotomy stimulated COX-2 activity, whereas gut manipulation led to an excessive cNOS activity and prostaglandin synthesis by COX-1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect