EFFECTS OF LIPOPOLYSACCHARIDE ON INTESTINAL INJURY - POTENTIAL ROLE OF NITRIC-OXIDE AND LIPID-PEROXIDATION

Nitric oxide can react with superoxide anion to form peroxynitrite, Th e resultant free radical can be rapidly protonated to yield even more toxic substances such as hydroxyl radical and nitric dioxide. The gene ration of either of these free radical species can promote lipid perox idation and subsequent tissue injury if they are formed in excessive a mounts. During sepsis, both nitric oxide synthesis and peroxynitrite p roduction 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 lipop olysaccharide (LPS) has on inducible nitric oxide synthase expression in the small intestine and to determine whether this is associated wit h lipid peroxidation or morphologic injury. When examined by Western i mmunoblot analysis, significantly more inducible nitric oxide synthase immunoreactivity was detected in the ileum than in the jejunum 5 hr a fter treatment with intraperitoneal LPS (1 and 20 mg/kg). Further, usi ng 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 mucos a after LPS (20 mg/kg) administration. However, LPS (20 mg/kg) resulte d in morphologic damage to both segments of the intestinal epithelium. These data indicate that the gut is a target during sepsis and that r egional differences exist within the small bowel with respect to induc tion of nitric oxide synthase and lipid peroxidation following LPS tre atment. Thus, while induction of nitric oxide synthase during endotoxi c shock may still represent a mechanism of local intestinal damage, it is not necessarily associated with enhanced lipid peroxidation. (C) 1 996 Academic Press, Inc.