ENDOTOXIN-INDUCED OXIDATIVE STRESS IN THE RAT SMALL-INTESTINE - ROLE OF NITRIC-OXIDE

Reactive oxygen species have been implicated in the gastrointestinal p athogenesis of septic and endotoxic shock. The objective of this study was to investigate the role of inducible nitric oxide synthase during endotoxin-induced formation of oxidants by cells of the small intesti ne. After intravenous Escherichia coil lipopolysaccharide (LPS) (1 mg/ kg) injection, nitric oxide production was measured as nitrosyl comple x formation in the ileum using electron paramagnetic resonance spectro scopy, Oxidative stress biomarkers were determined as duodenal mucosal -reduced thiols, the ileal lipid peroxidation and luminal free radical production using spin trapping methodology. Demonstration of nitrosyl complex formation commenced at 3 h and diminished 24 h post-LPS. Muco sal thiol levels were decreased at 3, 6, 12, and 18 h post-LPS treatme nt. At these lime points, the ileal lipid peroxidation also increased as did luminal formation of hydroxyl radical adduct. Nitric oxide synt hase inhibitors reversed the elevation of hydroxyl radical formation a nd reversed the decrease in mucosal-reduced thiol levels in the LPS-tr eated rats. Our data indicate that nitric oxide or its oxidant product (s), such as peroxynitrite, contribute to oxidative injury in the smal l intestine of rats treated with endotoxin.