Molecular and Cellular Biochemistry

, Volume 175, Issue 1–2, pp 117–123 | Cite as

Impaired phosphatidylcholine biosynthesis and ascorbic acid depletion in lung during lipopolysaccharide-induced endotoxaemia in guinea pigs

  • Enrique Benito
  • María A. Bosch


Injection of guinea pigs with a single dose of Escherichia coli lipopolysaccharide (3.2 mg/100 g) induces a reversible endotoxic shock that was evaluated by measuring plasma glucose levels and aspartate aminotransferase activity at 24 h after lipopolysaccharide injection. The hypoglycaemia and the increase in plasma aminotransferase activity observed, correlated with the alterations found during the recovery phase of endotoxic shock. When lipid peroxidation and some antioxidant systems were measured in lungs from treated animals, we only found differences in ascorbic acid content, that was decreased by 50%. Lipopolysaccharide treatment results in a depression of pulmonary phosphatidylcholine synthesis, that correlates with the surfactant deficiencies associated with respiratory illnesses in septic shock. Guinea pigs fed on a diet with a low content in ascorbic acid were more sensitive to endotoxin. In these animals we found no detectable levels of ascorbic acid in lung, whereas both vi tamin E lung levels and pulmonary phosphatidylcholine synthesis were significantly decreased. Our results point out the significance of ascorbic acid in the protection against oxidative lung injury associated to endotoxaemia, and validate our shock model for further studies on the mechanisms of this pathological condition. (Mol Cell Biochem 175: 117–123, 1997)

endotoxic shock lipopolysaccharide guinea pig lung phosphatidylcholine ascorbic acid 


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  1. 1.
    Luce JM: Pathogenesis and management of septic shock. Chest 91(6): 883–888, 1987Google Scholar
  2. 2.
    Harris RL, Musher DM, Bloom K, Gathe J, Rice L, Sugarman B, Williams TV, Young EJ: Manifestations of sepsis. Arch Intern Med 147: 1895–1906, 1987Google Scholar
  3. 3.
    Lewis JF, Jobe AH: Surfactant and the adult respiratory distress syndrome. Am Rev Respir Dis 148: 218–233, 1993Google Scholar
  4. 4.
    Goerke J: Lung surfactant. Biochim Biophys Acta 344: 241–261, 1974Google Scholar
  5. 5.
    Von Wichert P, Wiegers W, Stephan W, Eckert P, Riesner K: Altered metabolism of phospholipids in the lung of rats with peritonitis. Res Exp Med 172: 233–239, 1978Google Scholar
  6. 6.
    Idegami K, Mori K, Misumi A, Akagi M: Changes in alveolar stability and phospholipids in pulmonary surfactant in acute pancreatitis. Jap J Surg 13: 227–235, 1983Google Scholar
  7. 7.
    Bosch MA, Risco C, Municio AM: Effect of Escherichia coli lipopolysaccharide on phosphatidylcholine biosynthesis by rat lung and alveolar type II cells. Mol Cell Biochem 93: 167–172, 1990Google Scholar
  8. 8.
    Weiland JE, Davis WB, Holter JF, Mohammed JR, Dorinsky PM, Gadek JE: Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathophysiologic significance. Am Rev Respir Dis 133: 218–225, 1986Google Scholar
  9. 9.
    Holman RG, Maier RV: Superoxide production by neutrophils in a model of adult respiratory distress syndrome. Arch Surg 123: 1491–1495, 1988Google Scholar
  10. 10.
    Heffner JA, Repine JE: Pulmonary strategies of antioxidant defence. Am Rev Respir Dis 140: 531–534, 1989Google Scholar
  11. 11.
    Frei B, England L, Ames BN: Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci 86: 6377–6381, 1989Google Scholar
  12. 12.
    Burton GW, Traber MG, Vitamin E: antioxidant activity, biokinetics and bioavailability. Ann Rev Nutr 10: 357–382, 1990Google Scholar
  13. 13.
    Wong C, Flynn J, Demling RH: Role of oxygen radicals in endotoxininduced lung injury. Arch Surg 119: 77–82, 1984Google Scholar
  14. 14.
    Lowry OH, Rosenbrough NJ, Farr AL, Randall R: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275, 1951Google Scholar
  15. 15.
    Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47: 469–474, 1974Google Scholar
  16. 16.
    Barja de Quiroga G, López-Torres M, Pérez-Campo R, Rojas C. Simultaneous determination of two antioxidants, uric and ascorbic acid, in animal tissue by High-Performance Liquid Chromatography. Anal Biochem 199: 81–85, 1991Google Scholar
  17. 17.
    Vatassery GT, Brin MF, Fahn S, Kayden HJ, Traber M G: Effect of high doses of dietary vitamin E on the concentrations of vitamin E in several brain regions, plasma, liver, and adipose tissue of rats. J Neurochem 51: 621–623, 1988Google Scholar
  18. 18.
    Labarca C, Paigen K: A simple, rapid, and sensitive DNA assay procedure. Anal Biochem 102: 344–352, 1980Google Scholar
  19. 19.
    Bligh EG, Dyer WJ: A rapid method of total lipid extraction and purification. Can J Biochem Physio l 37: 911–917, 1959Google Scholar
  20. 20.
    Bosch MA, García R, Pagani R, Portolés MT, Díaz-Laviada I, Abarca S, Ainaga MJ, Risco C, Municio AM: Induction of reversible shock by Escherichia coli lipopolysaccharide in rats. Changes in serum and cell membrane parameters. Br J Exp Path 69: 805–812, 1988Google Scholar
  21. 21.
    Tsan M: Superoxide dismutase and pulmonary oxygen toxicity. Proc Soc Exp Biol Med 203: 286–290, 1993Google Scholar
  22. 22.
    Kong XJ, Fanburg BL: Regulation of Cu,Zn-Superoxide Dismutase in bovine pulmonary artery endothelial cells. J Cell Physiol 153: 491–497, 1992Google Scholar
  23. 23.
    McCay PB: Vitamin E: interaction with free radicals and ascorbate. Ann Rev Nutr 5: 323–340, 1985Google Scholar
  24. 24.
    Niki E: Vitamin C as an antioxidant in selected vitamins, minerals, and functional consequences of maternal malnutrition. World Rev Nutr Dietet 64: 1–30, 1991Google Scholar
  25. 25.
    Chow CK, Airriess GR, Changchit C. Increased vitamin E content in the lungs of chronic cigarette-smoked rats. Ann NY Acad Sci 570: 425–427, 1989Google Scholar
  26. 26.
    Rüstow B, Haupt R, Stevens PA, Kunze D: Type II pneumocytes secrete vitamin E together with surfactant lipids. Am J Physiol 265: L133–L139, 1993Google Scholar

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© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Enrique Benito
    • 1
  • María A. Bosch
    • 1
  1. 1.Department of Biochemistry and Molecular Biology, Faculty of ChemistryUniversidad ComplutenseMadridSpain

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