Ethyl pyruvate ameliorates ileus induced by bowel manipulation in mice.
BACKGROUND
Ethyl pyruvate (EP) improves survival, decreases proinflammatory cytokine expression, and ameliorates organ dysfunction in mice who have lethal sepsis or were subjected to hemorrhagic shock. Herein, we tested the hypothesis that treatment with EP can prevent the development of ileus after bowel manipulation, a phenomenon that is mediated by an inflammatory response in the bowel wall.


METHODS
C57Bl/6 mice underwent operative manipulation of the small intestine or were subjected to a sham procedure. Some of the mice subjected to gut manipulation were pre- and post-treated with 4 doses of EP (40 or 80 mg/kg per dose), whereas others received similar volumes of the vehicle for EP. Gastrointestinal transit of a nonabsorbable marker was assessed by gavaging the mice with the tracer 24 hours after operation and assessing its concentration 90 minutes later in bowel contents from the stomach, 10 equally long segments of small intestine, the cecum, and 2 equally long segments of colon. The contractile responses of ileal circular smooth muscle to graded concentrations of bethanechol were assessed by using standard organ bath methodology. Expression of interleukin-6 and inducible nitric oxide synthase transcripts in ileal muscularis propria was assessed by using the semiquantitative reverse transcriptase-polymerase chain reaction.


RESULTS
In sham-operated controls, the mean (+/- SE) geometric center for the transit marker was 10.0 +/- 0.5, whereas for vehicle-treated mice subject to bowel manipulation, the value for this parameter was 3.5 +/- 0.1 (P < .05). When mice subjected to bowel manipulation were treated with several 40 mg/kg doses of EP, the geometric center was 7.3 +/- 1.0 (P < .05 vs sham-operated group). Gut manipulation impaired intestinal smooth muscle contractility in vitro and increased steady-state levels of interleukin-6 and inducible nitric oxide synthase messenger RNA. Treatment with EP ameliorated these effects of gut manipulation.


CONCLUSIONS
EP warrants further evaluation as a therapeutic agent to ameliorate postoperative ileus.
Harada
Tomoyuki
T
Department of Critical Care Medicine, Pittsburgh, PA 15261, USA.
Moore
Beverley A
BA
Yang
Runkuan
R
Cruz
Ruy J
RJ
Delude
Russell L
RL
Fink
Mitchell P
MP
D000818:Animals; D004195:Disease Models, Animal; D005772:Gastrointestinal Transit; D045823:Ileus / Q000139:chemically induced* / Q000517:prevention & control*; D007421:Intestine, Small / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D011183:Postoperative Complications / Q000517:prevention & control; D011773:Pyruvates / Q000494:pharmacology*; D012016:Reference Values
D011773:Pyruvates; C046522:ethyl pyruvate