Inosine improves gut permeability and vascular reactivity in endotoxic shock

Francisco Garcia Soriano, Lucas Liaudet, Anita Marton, György Haskó, Clara Batista Lorigados, Edwin A. Deitch, Csaba Szabó

    Research output: Contribution to journalArticlepeer-review

    53 Scopus citations

    Abstract

    Objective: To investigate the effects of inosine administration on vascular reactivity, gut permeability, neutrophil accumulation and lipid peroxidation 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; b) inosine controls, which received inosine alone (100 mg/kg, ip); c) lipopolysaccharide (LPS)-treated animals, which received LPS (40 and 100 mg/kg, ip, depending on the experimental protocol); d) inosine pretreatment group, which received inosine (100 mg/kg, ip) 30 mins before LPS; and finally, e) inosine posttreatment group, which received inosine (100 mg/kg, ip) 60 mins after LPS. Measurements and Main Results: The passage of fluorescein isothiocyanate-conjugated dextran (4 kDa, FD4) was analyzed in everted gut ileal sacs incubated ex vivo as an index of gut permeability. LPS induced a significant intestinal hyperpermeability, and inosine exerted protective effects both in pre- and posttreatment regimens. Myeloperoxidase and malondialdehyde were also measured to study neutrophil accumulation and lipid peroxidation in selected tissues. Inosine, both in pre- and posttreatment regimens ameliorated the increases in myeloperoxidase and malondialdehyde in the lung and gut. LPS-treated animals showed decreased contractile and relaxant responses, and inosine pretreatment (but not posttreatment) partially improved these responses. Conclusions: Taken together, inosine has organ protective effects during shock. A significant portion of its protective action is maintained even in the posttreatment scenario.

    Original languageEnglish (US)
    Pages (from-to)703-708
    Number of pages6
    JournalCritical care medicine
    Volume29
    Issue number4
    DOIs
    StatePublished - 2001

    Keywords

    • Endothelial
    • Endotoxin
    • Gut
    • Inosine
    • Liver
    • Lung
    • Malondialdehyde
    • Myeloperoxidase
    • Permeability
    • Reactivity
    • Shock
    • Vascular

    ASJC Scopus subject areas

    • Critical Care and Intensive Care Medicine

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