Abstract
OBJECTIVES:Several compounds characterized by an olefin linkage conjugated to a carbonyl group have anti-inflammatory properties. The diuretic ethacrynic acid (EA) is a compound of this type. Herein, we tested the hypothesis that ethacrynic acid can modulate the development of ileus after bowel manipulation.METHODS:Groups (n=9) of male C57Bl/6 mice underwent surgical manipulation of the small intestine using a pair of cotton-tipped applicators (MAN). Control animals (CONT) did not undergo any surgical intervention or receive treatment. MAN mice were pre- and post-treated with four intraperitoneal doses of phosphate buffered saline (PBS), EA1 (1mg/kg per dose), or EA10 (10mg/kg per dose). Gastrointestinal transit of non-absorbable FITC-labeled dextran was assessed by gavaging the mice with the tracer 24h after operation and assessing FD70 concentration 120 min later in the bowel contents from the stomach, 10 equally long segments of small intestine, cecum, and two equally long segments of colon. The geometric center for the tracer was calculated for each animal. Expression of interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) transcripts in the ileal muscularis propria was assessed using semiquantitative reverse transcriptase-polymerase chain reaction.RESULTS:In control animals, the mean (±SE) geometric center for the transit marker was 9.89±0.47, whereas it was 4.59±0.59 for PBS-treated animals (p<0.05 vs CONT). The geometric center for pre- post treatment with low (1mg/kg) and high (10mg/kg) doses of ethacrynic acid were 7.23±0.97 and 5.15±0.57, respectively. Compared to PBS, treatment with ethacrynic acid (1mg/kg) significantly decreased manipulation-induced IL-6 and iNOS mRNA expression in the wall of the small bowel.CONCLUSIONS:Pre- and post-treatment with ethacrynic acid ameliorates ileus and modulates inflammation in the gut wall induced by bowel manipulation.
Highlights
Manipulation of the bowel during abdominal surgery inevitably leads to a period of impairment of gastrointestinal (GI) tract peristalsis
Ileus is generally accepted as a normal response to abdominal surgery, it is a factor that contributes to discomfort, abdominal distention, respiratory compromise, nausea, and emesis in the post-operative period [1,2,3]
Gastrointestinal transit In the control group, the entericallyadministered fluorescent tracer was rapidly transported in an aboral direction within the intestine such that the peak signal 90 min after administration was in the distal ileum and colon
Summary
Manipulation of the bowel during abdominal surgery inevitably leads to a period of impairment of gastrointestinal (GI) tract peristalsis. Ileus is generally accepted as a normal response to abdominal surgery, it is a factor that contributes to discomfort, abdominal distention, respiratory compromise, nausea, and emesis in the post-operative period [1,2,3]. No potential conflict of interest was reported. Received for publication on October 28, 2017. Accepted for publication on April 6, 2018
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