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 Szabo

Research output: Contribution to journalArticle

49 Citations (Scopus)

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
StatePublished - 2001
Externally publishedYes

Fingerprint

Inosine
Capillary Permeability
Septic Shock
Lipopolysaccharides
Malondialdehyde
Lipid Peroxidation
Peroxidase
Shock
Permeability
Neutrophils
Endotoxins
Blood Vessels
Prospective Studies

Keywords

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

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Garcia Soriano, F., Liaudet, L., Marton, A., Haskó, G., Batista Lorigados, C., Deitch, E. A., & Szabo, C. (2001). Inosine improves gut permeability and vascular reactivity in endotoxic shock. Critical Care Medicine, 29(4), 703-708.

Inosine improves gut permeability and vascular reactivity in endotoxic shock. / Garcia Soriano, Francisco; Liaudet, Lucas; Marton, Anita; Haskó, György; Batista Lorigados, Clara; Deitch, Edwin A.; Szabo, Csaba.

In: Critical Care Medicine, Vol. 29, No. 4, 2001, p. 703-708.

Research output: Contribution to journalArticle

Garcia Soriano, F, Liaudet, L, Marton, A, Haskó, G, Batista Lorigados, C, Deitch, EA & Szabo, C 2001, 'Inosine improves gut permeability and vascular reactivity in endotoxic shock', Critical Care Medicine, vol. 29, no. 4, pp. 703-708.
Garcia Soriano F, Liaudet L, Marton A, Haskó G, Batista Lorigados C, Deitch EA et al. Inosine improves gut permeability and vascular reactivity in endotoxic shock. Critical Care Medicine. 2001;29(4):703-708.
Garcia Soriano, Francisco ; Liaudet, Lucas ; Marton, Anita ; Haskó, György ; Batista Lorigados, Clara ; Deitch, Edwin A. ; Szabo, Csaba. / Inosine improves gut permeability and vascular reactivity in endotoxic shock. In: Critical Care Medicine. 2001 ; Vol. 29, No. 4. pp. 703-708.
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AU - Garcia Soriano, Francisco

AU - Liaudet, Lucas

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AU - Haskó, György

AU - Batista Lorigados, Clara

AU - Deitch, Edwin A.

AU - Szabo, Csaba

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AB - 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.

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