Products of cyclooxygenase-2 catalysis regulate postoperative bowel motility.

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Josephs MD, Cheng G, Ksontini R, Moldawer LL, Hocking MP

Products of cyclooxygenase-2 catalysis regulate postoperative bowel motility.

J Surg Res. 1999 Sep;86(1):50-4.

PubMed ID

10452868 [ View in PubMed

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Abstract

Laparotomy involving manipulation of the small intestine causes injury, initiating an inflammatory cascade in the small bowel wall, which generates eicosanoids and proinflammatory cytokines. We have shown that ketorolac and salsalate, nonselective cyclooxygenase (COX) inhibitors, ameliorate postoperative small bowel ileus in a rodent model. Others have shown that interleukin-1 receptor antagonism improves postoperative gastric emptying. We examined whether inhibition of the proinflammatory cytokines, tumor necrosis factor alpha (TNFalpha) and interleukin-1 (IL-1), or selective blockade of cyclooxygenase-2 (COX-2), the COX isoform induced during inflammation, would accelerate postoperative small bowel transit in our model. Duodenostomy tubes were inserted into male Sprague-Dawley rats. One week later, animals were randomized to receive TNF-binding protein (TNF-bp), IL-1 receptor antagonist (IL-1ra), or saline (NS) prior to standardized laparotomy. Additional rats were gavaged preoperatively with a selective COX-2 inhibitor (NS-398) or NS. Small intestinal transit was measured as the geometric center (GC) of distribution of (51)CrO(4) at 30 min, 3 h, or 6 h (n = 5-9 rats/group) following laparotomy. Selective inhibition of COX-2 significantly increased postoperative small bowel transit compared to controls (GC 2.9 +/- 0.3 vs 2.2 +/- 0.1 at 30 min, GC 2.9 +/- 0.3 vs 2.5 +/- 0.2 at 3 h, and GC 3.3 +/- 0.3 vs 2.8 +/- 0.2 at 6 h, P < 0.05). In contrast, neither TNF-bp nor IL-1ra altered postoperative small intestinal transit in this model. Use of selective COX-2 inhibitors may accelerate recovery of postoperative bowel dysmotility without the undesirable effects (e.g., gastrointestinal irritation and anti-platelet effect) of nonselective COX inhibitors.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Salsalate	Prostaglandin G/H synthase 1	Protein	Humans	Yes	Inhibitor	Details
Salsalate	Prostaglandin G/H synthase 2	Protein	Humans	Yes	Inhibitor	Details