Endotoxin-induced ileal mucosal injury and nitric oxide dysregulation are temporally dissociated.
Am J Respir Crit Care Med
; 161(5): 1705-12, 2000 May.
Article
em En
| MEDLINE
| ID: mdl-10806178
ABSTRACT
Despite recent investigations, the mechanisms responsible for intestinal epithelial injury during endotoxemia remain unclear. The present study tests the hypothesis that epithelial necrosis and/or apoptosis correlate with nitric oxide (NO) dysregulation in a nonischemic model of sepsis-induced ileal injury. To test this hypothesis, a well-established in situ, autoperfused, feline ileal preparation was employed. After endotoxin (lipopolysaccharide [LPS], 3 mg/ kg, intravenously; n = 9) or vehicle (control; n = 5) treatment, ileal segments were obtained at baseline, 2 and 4 h for simultaneous evaluations of cellular and mitochondrial ultrastructure, immunoprevalence of inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (a stable biomarker of peroxynitrite), and histochemical evidence of apoptosis. Epithelial necrosis was prominent by 2 h post-LPS, despite unaltered global ileal tissue oxygen content, blood volume, and blood flow. Significant evidence of apoptosis and increases in the immunoprevalence of iNOS and 3-nitrotyrosine were not evident until 4 h post-LPS. These results suggest that the early ileal mucosal necrosis may be due to LPS-induced activation of inflammatory pathways and/or microcirculatory disturbances, whereas NO dysregulation may participate in later events, including protein nitration and epithelial apoptosis.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Sepse
/
Íleo
/
Mucosa Intestinal
/
Óxido Nítrico
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article