Antioxidant Activity in the Therapy of Sepsis: From Experimental Data to Clinical Practice

  • G. P. Novelli
  • R. Casali
  • S. Falsini
  • E. Pieraccioli


An antioxidant is defined as any substance which delays or prevents the oxidation of a substrate when it is present in small amounts relative to the amount of the substrate itself. Antioxidants are active at several levels of the oxidative sequence and their mechanism of action may be unique.


Septic Shock Patient Antioxidant Therapy Extravascular Lung Water Circ Shock Traumatic Shock 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lefer AM, Araki H, Okamatsu S (1981) Beneficial actions of a free radical scavenger in traumatic shock and myocardial ischemia. Circ Shock 8:273–282PubMedGoogle Scholar
  2. 2.
    Novelli GP, De Gaudio AR (1983) Oxygen free-radicals in shock states. Elsevier, AmsterdamGoogle Scholar
  3. 3.
    De Gaudio AR, Sarti A, Palmarini M et al (1983) Prevenzione dello shock sperimentale mediante uno scavenger di radicali liberi: il glutatione ridotto. Acta Anaesth Ital 34:501–507Google Scholar
  4. 4.
    Saez JC, Ward PH, Gunther B et al (1984) Superoxide radical involvement in the pathogenesis of burn shock. Circ Shock 12:229–233PubMedGoogle Scholar
  5. 5.
    Novelh GP (1992) Oxygen radicals in experimental shock: effects of spin-trapping nitrones in ameliorating shock pathophysiology. Crit Care Med 20:499–507CrossRefGoogle Scholar
  6. 6.
    Novelh GP, Angiolini P, Tani R et al (1985) Phenyl-t-butyl-nitrone is active against traumatic shock in rats. Free Radic Res Commun 1:321–327CrossRefGoogle Scholar
  7. 7.
    Goode HF, Webster NR (1993) Free radicals and antioxidants in sepsis. Crit Care Med 21: 1770–1776PubMedCrossRefGoogle Scholar
  8. 8.
    Schiller HJ, Reilly PM, Bulkley GB (1993) Antioxidant therapy. Crit Care Med 21:S92–102PubMedCrossRefGoogle Scholar
  9. 9.
    Rice-Evans CA, Diplock AT (1993) Current status of antioxidant therapy. Free Radic Biol Med 15:77–96PubMedCrossRefGoogle Scholar
  10. 10.
    Bone RC (1992) Inhibitors of complement and neutrophils: a critical evaluation of their role in the treatment of sepsis. Crit Care Med 20:891–898PubMedCrossRefGoogle Scholar
  11. 11.
    Youn YK, Lalonde C, Demling R (1991) Use of antioxidant therapy in shock and trauma. Circ Shock 35:245–249PubMedGoogle Scholar
  12. 12.
    Mannion D, Fitzpatrick GJ, Feeley M (1994) Role of xanthine oxidase inhibition in survival from hemorrhagic shock. Circ Shock 42:39–43PubMedGoogle Scholar
  13. 13.
    Sahm AS (1991) Protection against stress-induced acute gastric mucosal injury by free-radical scavengers. Intensive Care Med 17:455–460CrossRefGoogle Scholar
  14. 14.
    Tani T, Aoki H, Yoshioka T (1993) Treatment of septic shock with a protease inhibitor in a canine model: a prospective, randomized, controlled trial. Crit Care Med 21:925–930PubMedCrossRefGoogle Scholar
  15. 15.
    Novelli GP, Innocenti P, Livi P (1993) II gabesato mesilato (Foy) nuovo antiproteasico sintetico nel trattamento dello shock. Studio multicentrico italiano. Minerva Anestesiol 58: 247–253Google Scholar
  16. 16.
    Novelh GP, Casali R, Bonizzoh M et al (1995) Azione antiossidante del gabesato mesilato (Foy) in un modello sperimentale di shock. Minerva Anestesiol 60 (in press)Google Scholar
  17. 17.
    Sanfey H, Bulkley GB, Cameron JL (1985) The pathogenesis of acute pancreatitis. The source and the role of oxygen-derived free radicals in three different experimental models. Ann Surg 201:633–639PubMedCrossRefGoogle Scholar
  18. 18.
    Fujishima S, Aikawa N (1995) Neutrophil-mediated tissue injury and its modulation. Intensive Care Med 21:277–285PubMedCrossRefGoogle Scholar
  19. 19.
    Wolbarsht ML, Fridovich I (1989) Hyperoxia during reperfusion is a factor in reperfusion injury. Free Radic Biol Med 6:61–62PubMedCrossRefGoogle Scholar
  20. 20.
    Drugas GT, Paidas CN, Yahanda AM et al (1991) Conjugated desferoxamine attenuates hepatic microvascular injury following ischemia-reperfusion. Circ Shock 34:278–283PubMedGoogle Scholar
  21. 21.
    Fleckenstein AE, Smith SL, Linseman KL et al (1991) Comparison of the efficacy of mechanistically different antioxidants in the rat hemorrhagic shock model. Circ Shock 35: 223–230PubMedGoogle Scholar
  22. 22.
    Zhao W, Richardson JS, Mombourquette MJ et al (1995) An in vitro EPR study of the free radical scavenging actions of the lazaroid antioxidants U-74500 A and U-78517 F. Free Radic Biol Med 19:21–30PubMedCrossRefGoogle Scholar
  23. 23.
    Johnson G, Lefer AM (1990) Protective effects of a novel 21-aminosteroid during splanchnic artery occlusion shock. Circ Shock 30:155–164PubMedGoogle Scholar
  24. 24.
    Inove M, Saito Y, Hirata E et al (1987) Regulation of redox states of plasma proteins by metabolism and transport of glutathione and related compounds. J Prot Chem 6:207–225Google Scholar
  25. 25.
    Meister A (1988) Glutathione metabohsm and its selective modification. J Biol Chem 263: 17205–17208PubMedGoogle Scholar
  26. 26.
    Robinson MK, Ahn MS, Rounds JD (1992) Parenteral glutathione monoester enhaucas tissue antioxidant stores. JPEN J Parenter Enteral Nutr 16:413–418PubMedCrossRefGoogle Scholar
  27. 27.
    Griffith OW, Meister A (1985) Origin and turnover of mitochondrial glutathione. Proc Natl Acad Sci USA 82:4668–4672PubMedCrossRefGoogle Scholar
  28. 28.
    Hagen TM, Yee AWT, Jones DP (1988) Glutathione uptake and protection against oxidative injury in isolated kidney cells. Kidney Int 34:74–81PubMedCrossRefGoogle Scholar
  29. 29.
    Falsini S, Celiai MP, Angiolini P et al (1994) Glutatione ridotto e L-cisteina nello shock endotossinico nel ratto. Minerva Anestesiol 60:413–418PubMedGoogle Scholar
  30. 30.
    Novelli GP, Falsini S, Bracciotti G (1991) Exogenous glutathione increases endurance to muscle effort in mice. Pharmacol Res 23:149–155PubMedCrossRefGoogle Scholar
  31. 31.
    Scardi S, Rossi R, Pieraccioli E et al (1993) Reduced glutathione prevents lipid peroxidation as expressed by ethane exhalation during aortic surgery in man. Minerva Anestesiol 59:S2–215Google Scholar
  32. 32.
    Mediati RD, Girardi G, Rossi R et al (1993) Glutathione administration prevents the increase of extravascular lung water during ischemia and reperfusion in man. Minerva Anestesiol 59: S2–214Google Scholar
  33. 33.
    Paternostro E, Scardi S, Pellegrini G (1993) Lung lipoperoxidative stress during hyperoxic anaesthesia: protective effects of reduced glutathione. Minerva Anestesiol 59:S2–213Google Scholar
  34. 34.
    Novelli GP, Casali R, Bonizzoli M et al (1993) Aumento della permeabilità capillare provocato dall’endotossina: protezione con antiossidanti e glutatione. Minerva Anestesiol 59: 211–216PubMedGoogle Scholar
  35. 35.
    Di Filippo A, Paternostro E, Scardi S et al (1992) Insufficienza multipla d’organo sperimentale nel ratto: effetti protettivi del glutatione ridotto. Acta Anaesth Ital 43:358–369Google Scholar
  36. 36.
    Novelli GP, Melani AM, Consales G et al (1994) Antioxidant drugs in cerebral and spinal ischemia. Minerva Anestesiol 60:543–546PubMedGoogle Scholar
  37. 37.
    Novelh GP (1990) I radicali liberi nello shock e in alcuni quadri ad esso correlati. In Albano et al (eds): Radicali liberi in patologia — nuovi orientamenti patogenetici e strategie chniche. Prag 6–9 December 1990Google Scholar
  38. 38.
    Aruoma OI, Halliwell B, Hoey BM (1989) The antioxidant properties of n-acetyl-cysteine. Free Radic Biol Med 6:593–597PubMedCrossRefGoogle Scholar
  39. 39.
    Bernard GR (1991) N-acetylcysteine in experimental and clinical acute lung injury. Am J Med 91:S3 54–59CrossRefGoogle Scholar
  40. 40.
    Spies CD, Reinahart K, Witt I et al (1994) Influence of n-acetylcysteine on indirect indicators of tissue oxygenation in septic shock patients: results from a prospective, randomized, double- blind study. Crit Care Med 22:1738–1746PubMedGoogle Scholar
  41. 41.
    Zimmerman JJ (1992) Radical viewpoints in critical illness. Crit Care Med 20:448–449PubMedCrossRefGoogle Scholar
  42. 42.
    Yamauchi N, Watanabe N, Kuriyama H et al (1990) Suppressive effects of intracellular glutathione on hydroxyl radical production induced by tumor necrosis factor. Int J Cancer 46: 884–888PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia, Milano 1996

Authors and Affiliations

  • G. P. Novelli
  • R. Casali
  • S. Falsini
  • E. Pieraccioli

There are no affiliations available

Personalised recommendations