Role of oxidative stress in the pathogenesis of septic ileus in mice.
We investigated the role of oxidative stress in the pathogenesis of septic ileus. Sepsis was induced by intraperitoneal (i.p.) injection of lipopolysaccharides (LPS, 20 mg kg(-1)) in mice. The effect of two i.p. injections of superoxide dismutase [polyethylene glycol (PEG)-SOD, 4000 U kg(-1)] and catalase (PEG-CAT, 15,000 U kg(-1)) was investigated on gastric emptying, intestinal transit and total nitrite plasma concentrations. We also performed immunohistochemical experiments on gastric and ileal tissue. LPS significantly delayed gastric emptying and intestinal transit while plasma nitrite levels increased. Polyethylene glycol (PEG)-SOD reversed the endotoxin-induced delay in gastric emptying and improved the delay in intestinal transit without effect on plasma nitrite levels. PEG-CAT slightly improved the delay in gastric emptying without effect on intestinal transit. Immunohistochemistry showed the presence of nitrotyrosine (NT) and 4-hydroxy-2-nonenal (HNE) in the gastric and ileal mucosa of LPS-treated mice. Treatment with PEG-SOD or PEG-CAT of LPS mice diminished the presence of NT or HNE in both tissues. In addition, LPS induced a significant increase in inducible nitric oxide synthase (iNOS)-positive residential macrophages in the external musculature of stomach and ileum, which significantly decreased after PEG-SOD or PEG-CAT treatment. The present results support a role for oxidative and nitrosative stress in the pathogenesis of septic ileus in mice.
de Winter
B Y
BY
Division of Gastroenterology, Faculty of Medicine, University of Antwerp (campus Drie Eiken), Universiteitsplein 1, 2610 Antwerp, Belgium. benedicte.dewinter@ua.ac.be
van Nassauw
L
L
de Man
J G
JG
de Jonge
F
F
Bredenoord
A J
AJ
Seerden
T C
TC
Herman
A G
AG
Timmermans
J-P
JP
Pelckmans
P A
PA
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D004195:Disease Models, Animal; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology; D045823:Ileus / Q000139:chemically induced / Q000503:physiopathology*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000502:physiology*; D018805:Sepsis / Q000139:chemically induced / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D000447:Aldehydes; D000975:Antioxidants; D008070:Lipopolysaccharides; D009573:Nitrites; C002744:3-nitrotyrosine; D014443:Tyrosine; D002374:Catalase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D013482:Superoxide Dismutase; C027576:4-hydroxy-2-nonenal