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Protective effect of exogenous nitrite in postoperative ileus.

Abstract：

BACKGROUND AND PURPOSE:As the pathogenesis of postoperative ileus (POI) involves inflammation and oxidative stress, comparable to ischaemia/reperfusion injury which can be ameliorated with nitrite, we investigated whether nitrite can protect against POI and explored the mechanisms involved. EXPERIMENTAL APPROACH:We used intestinal manipulation (IM) of the small intestine to induce POI in C57BL/6J mice. Sodium nitrite (48 nmol) was administered intravenously just before IM. Intestinal transit was assessed using fluorescent imaging. Bethanechol-stimulated jejunal circular muscle contractions were measured in organ baths. Inflammatory parameters, neutrophil infiltration, inducible NOS (iNOS) activity, reactive oxygen species (ROS) levels, mitochondrial complex I activity and cGMP were measured in the intestinal muscularis. KEY RESULTS:Pre-treatment with nitrite markedly improved the delay in intestinal transit and restored the reduced intestinal contractility observed 24 h following IM. This was accompanied by reduced protein levels of TNF-α, IL-6 and the chemokine CCL2, along with reduced iNOS activity and ROS levels. The associated neutrophil influx at 24 h was not influenced by nitrite. IM reduced mitochondrial complex I activity and cGMP levels; treatment with nitrite increased cGMP levels. Pre-treatment with the NO scavenger carboxy-PTIO or the soluble guanylyl cyclase inhibitor ODQ abolished nitrite-induced protective effects. CONCLUSIONS AND IMPLICATIONS:Exogenous nitrite deserves further investigation as a possible treatment for POI. Nitrite-induced protection of POI in mice was dependent on NO and this effect was not related to inhibition of mitochondrial complex I, but did involve activation of soluble guanylyl cyclase.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Cosyns SM,Shiva S,Lefebvre RA

doi

10.1111/bph.13255

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

4864-74

issue

20

eissn

0007-1188

issn

1476-5381

journal_volume

172

pub_type

杂志文章

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