title: Effects of lipopolysaccharide on intestinal injury; potential role of nitric oxide and lipid peroxidation.
abstract: Nitric oxide can react with superoxide anion to form peroxynitrite. The resultant free radical can be rapidly protonated to yield even more toxic substances such as hydroxyl radical and nitric dioxide. The generation of either of these free radical species can promote lipid peroxidation and subsequent tissue injury if they are formed in excessive amounts. During sepsis, both nitric oxide synthesis and peroxynitrite production are substantially enhanced in a variety of tissues, effects which favor the development of lipid peroxidation. Consequently, this study was undertaken in conscious rats, to ascertain what effect lipopolysaccharide (LPS) has on inducible nitric oxide synthase expression in the small intestine and to determine whether this is associated with lipid peroxidation or morphologic injury. When examined by Western immunoblot analysis, significantly more inducible nitric oxide synthase immunoreactivity was detected in the ileum than in the jejunum 5 hr after treatment with intraperitoneal LPS (1 and 20 mg/kg). Further, using the thiobarbituric acid assay as an index of lipid peroxidation, it was demonstrated that significantly more thiobarbituric acid reactive substances were present in the ileal mucosa than in the jejunal mucosa after LPS (20 mg/kg) administration. However, LPS (20 mg/kg) resulted in morphologic damage to both segments of the intestinal epithelium. These data indicate that the gut is a target during sepsis and that regional differences exist within the small bowel with respect to induction of nitric oxide synthase and lipid peroxidation following LPS treatment. Thus, while induction of nitric oxide synthase during endotoxic shock may still represent a mechanism of local intestinal damage, it is not necessarily associated with enhanced lipid peroxidation.
authors.affiliation: Department of Surgery, University of Texas Medical School, Houston 77030, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Mercer
authors.forename: G S
authors.initials: GS
authors.lastname: Smith
authors.forename: J M
authors.initials: JM
authors.lastname: Cross
authors.forename: D H
authors.initials: DH
authors.lastname: Russell
authors.forename: L
authors.initials: L
authors.lastname: Chang
authors.forename: J
authors.initials: J
authors.lastname: Cacioppo
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000473:pathology / Q000503:physiopathology*; D015153:Blotting, Western; D004790:Enzyme Induction; D004927:Escherichia coli Infections / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D017665:Hydroxyl Radical / Q000378:metabolism; D007082:Ileum; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D007527:Isoenzymes / Q000096:biosynthesis; D007583:Jejunum; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000633:toxicity*; D008871:Microvilli / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014617:Vacuoles / Q000473:pathology / Q000648:ultrastructure
chemical_list: D007527:Isoenzymes; D008070:Lipopolysaccharides; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D019001:Nitric Oxide Synthase