Journal
CRITICAL CARE MEDICINE
Volume 29, Issue 4, Pages 703-708Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00003246-200104000-00001
Keywords
inosine; shock; endotoxin; gut; vascular; endothelial; permeability; reactivity; lung; liver; myeloperoxidase; malondialdehyde
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Funding
- NIGMS NIH HHS [R43GM59560, R29GM54773] Funding Source: Medline
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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; h) 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.
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