Inosine improves gut permeability and vascular reactivity in endotoxic shock

Objective: To investigate the effects of inosine administration on vascular reactivity, gut permeability, neutrophil accumulation and lipid peroxidati on in tissues in murine endotoxin shock. Design:Randomized, prospective laboratory study. Setting: Research laboratory. Subjects: BALB/c mice 6-8 wks age. Interventions: BALB/c mice were randomly assigned to one of five groups: a) vehicle controls, which received saline intraperitoneally; h) inosine cont rols, which received inosine alone (100 mg/kg, ip); c) lipopolysaccharide ( LPS)-treated animals, which received LPS (40 and 100 mg/kg, ip, depending o n the experimental protocol); d) inosine pretreatment group, which received inosine (100 mg/kg, ip) 30 mins before LPS; and finally, e) inosine posttr eatment group, which received inosine (100 mg/kg, ip) 60 mins after LPS. Measurements and Main Results: The passage of fluorescein isothiocyanate-co njugated dextran (4 kDa, FD4) was analyzed in everted gut ileal sacs incuba ted ex vivo as an index of gut permeability, LPS induced a significant inte stinal hyperpermeability, and inosine exerted protective effects both in pr e- and posttreatment regimens, Myeloperoxidase and malondialdehyde were als o measured to study neutrophil accumulation and lipid peroxidation in selec ted tissues, Inosine, both in pre- and posttreatment regimens ameliorated t he increases in myeloperoxidase and malondialdehyde in the lung and gut. LP S-treated animals showed decreased contractile and relaxant responses, and inosine pretreatment (but not posttreatment) partially improved these respo nses. Conclusions:Taken together, inosine has organ protective effects during sho ck, A significant portion of its protective action is maintained even in th e posttreatment scenario.