Inosine reduces systemic inflammation and improves survival in septic shock induced by cecal ligation and puncture

Details

Serval ID
serval:BIB_EC1F6FB12504
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Inosine reduces systemic inflammation and improves survival in septic shock induced by cecal ligation and puncture
Journal
American Journal of Respiratory and Critical Care Medicine
Author(s)
Liaudet  L., Mabley  J. G., Soriano  F. G., Pacher  P., Marton  A., Hasko  G., Szabo  C.
ISSN
1073-449X (Print)
Publication state
Published
Issued date
10/2001
Volume
164
Number
7
Pages
1213-20
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Oct 1
Abstract
Inosine is a naturally occurring purine formed from the breakdown of adenosine. Here we have evaluated the effects of inosine in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Mice subjected to CLP were treated with either inosine (100 mg/kg, intraperitoneally) or vehicle 1 h before and 6 h after CLP. After 12 h tumor necrosis factor alpha, interleukin 6 (IL-6), and IL-10 were measured in plasma. Biochemical markers of organ damage, liver NAD+/NADH (indicator of the mitochondrial redox state), plasma nitrate, tissue myeloperoxidase (MPO, indicator of neutrophil accumulation) and malondialdehyde (MDA, indicator of lipid peroxidation), liver and lung chemokines (macrophage inflammatory protein 1alpha [MIP-1alpha] and MIP-2), and ex vivo vascular reactivity in aortic rings were also measured. Mice treated with inosine had significantly lower levels of circulating cytokines. Organ damage was significantly reduced by inosine treatment, which was associated at the tissue level with an increased hepatic NAD+/NADH ratio, decreased MPO activity in the lung, reduced MDA formation in the gut and liver, and decreased MIP-1alpha and MIP-2 in the lung and liver. Furthermore, inosine significantly improved endothelium-dependent relaxant responses of aortic rings. These effects were associated with significant improvement of the survival of CLP mice treated with inosine, an effect that was still observed when inosine treatment was delayed 1 h after CLP, especially when it was associated with appropriate antibiotic treatment. Thus, inosine reduced systemic inflammation, organ damage, tissue dysoxia, and vascular dysfunction, resulting in improved survival in septic shock.
Keywords
Animals Biological Markers/blood Cecum Cytokines/blood Inflammation/blood/*drug therapy/etiology Inosine/*therapeutic use Ligation Male Mice Mice, Inbred BALB C Punctures Shock, Septic/blood/*drug therapy/etiology/*mortality Survival Rate
Pubmed
Web of science
Create date
24/01/2008 17:01
Last modification date
20/08/2019 16:14
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