1887

Abstract

Antioxidants are known to exhibit numerous health benefits including anti-ageing, anti-apoptotic and immuno-stimulatory effects. However, we present the data showing counterproductive effects of therapeutically relevant antioxidants on bacterial clearance by the immune system in a murine peritonitic model. The antioxidants ascorbic acid, glutathione and -acetylcysteine augmented morbidity and mortality in mice carrying -induced acute bacterial peritonitis. Treatment of peritonitic mice with antioxidants significantly increased their bacterial load in the range of 0.3–2 logs. Antioxidant administration to peritonitic mice resulted in decreased numbers of macrophages, B-cells and dendritic cells at the primary site of infection and increased neutrophil infiltration. Serum TNF-α levels were also decreased in antioxidant-treated peritonitic mice. experiments showed that antioxidants reduced the phagocytic efficacy of peritoneal macrophages by ~60–75 % and also decreased -induced oxidative burst in macrophages cells. Taken together, our data indicate that the antioxidants increased the severity of peritonitis by decreasing the phagocytic efficiency, oxidative burst, and TNF-α production, and increasing neutrophil infiltration. Based on these results, we propose that antioxidant supplementation during the course of bacterial infection is not recommended as it could be detrimental for the host. In addition, the present study underlines the importance of timing and context of antioxidant administration rather than indiscriminate usage to gain the best possible therapeutic advantage of these redox compounds.

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2014-03-01
2019-10-18
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References

  1. Aitio M. L. . ( 2006; ). N-acetylcysteine-passe-partout or much ado about nothing. ? Br J Clin Pharmacol 61:, 5–15.[CrossRef]
    [Google Scholar]
  2. Albesa I. , Becerra M. C. , Battán P. C. , Páez P. L. . ( 2004; ). Oxidative stress involved in the antibacterial action of different antibiotics. . Biochem Biophys Res Commun 317:, 605–609. [CrossRef] [PubMed]
    [Google Scholar]
  3. Billips B. K. , Forrestal S. G. , Rycyk M. T. , Johnson J. R. , Klumpp D. J. , Schaeffer A. J. . ( 2007; ). Modulation of host innate immune response in the bladder by uropathogenic Escherichia coli . . Infect Immun 75:, 5353–5360. [CrossRef] [PubMed]
    [Google Scholar]
  4. Blot S. , De Waele J. J. . ( 2005; ). Critical issues in the clinical management of complicated intra-abdominal infections. . Drugs 65:, 1611–1620. [CrossRef] [PubMed]
    [Google Scholar]
  5. Brinkmann V. , Reichard U. , Goosmann C. , Fauler B. , Uhlemann Y. , Weiss D. S. , Weinrauch Y. , Zychlinsky A. . ( 2004; ). Neutrophil extracellular traps kill bacteria. . Science 303:, 1532–1535. [CrossRef] [PubMed]
    [Google Scholar]
  6. Brunelli L. , Crow J. P. , Beckman J. S. . ( 1995; ). The comparative toxicity of nitric oxide and peroxynitrite to Escherichia coli . . Arch Biochem Biophys 316:, 327–334. [CrossRef] [PubMed]
    [Google Scholar]
  7. Bump E. A. , al-Sarraf R. , Pierce S. M. , Coleman C. N. . ( 1992; ). Elevation of mouse kidney thiol content following administration of glutathione. . Radiother Oncol 23:, 21–25. [CrossRef] [PubMed]
    [Google Scholar]
  8. Butler J. , Hoey B. M. . ( 1993; ). Redox cycling drugs and DNA damage. . In DNA and Free Radicals, pp. 243–265. Edited by Halliwell B. , Aruoma O. I. . . London:: Ellis Horwood;.
    [Google Scholar]
  9. Castro L. , Rodriguez M. , Radi R. . ( 1994; ). Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide. . J Biol Chem 269:, 29409–29415.[PubMed]
    [Google Scholar]
  10. Checker R. , Sharma D. , Sandur S. K. , Subrahmanyam G. , Krishnan S. , Poduval T. B. , Sainis K. B. . ( 2010; ). Plumbagin inhibits proliferative and inflammatory responses of T cells independent of ROS generation but by modulating intracellular thiols. . J Cell Biochem 110:, 1082–1093. [CrossRef] [PubMed]
    [Google Scholar]
  11. Chen Y. H. , Xu D. X. , Zhao L. , Wang H. , Wang J. P. , Wei W. . ( 2006; ). Ascorbic acid protects against lipopolysaccharide-induced intra-uterine fetal death and intra-uterine growth retardation in mice. . Toxicology 217:, 39–45. [CrossRef] [PubMed]
    [Google Scholar]
  12. Dunn D. L. , Barke R. A. , Knight N. B. , Humphrey E. W. , Simmons R. L. . ( 1985; ). Role of resident macrophages, peripheral neutrophils, and translymphatic absorption in bacterial clearance from the peritoneal cavity. . Infect Immun 49:, 257–264.[PubMed]
    [Google Scholar]
  13. Dwyer D. J. , Kohanski M. A. , Collins J. J. . ( 2009; ). Role of reactive oxygen species in antibiotic action and resistance. . Curr Opin Microbiol 12:, 482–489. [CrossRef] [PubMed]
    [Google Scholar]
  14. Ehlers M. R. . ( 2000; ). CR3: a general purpose adhesion-recognition receptor essential for innate immunity. . Microbes Infect 2:, 289–294. [CrossRef] [PubMed]
    [Google Scholar]
  15. Fischbach M. A. , Walsh C. T. . ( 2009; ). Antibiotics for emerging pathogens. . Science 325:, 1089–1093. [CrossRef] [PubMed]
    [Google Scholar]
  16. Foucault C. , Brouqui P. . ( 2007; ). How to fight antimicrobial resistance. . FEMS Immunol Med Microbiol 49:, 173–183. [CrossRef] [PubMed]
    [Google Scholar]
  17. Goswami M. , Jawali N. . ( 2007; ). Glutathione-mediated augmentation of β-lactam antibacterial activity against Escherichia coli . . J Antimicrob Chemother 60:, 184–185. [CrossRef] [PubMed]
    [Google Scholar]
  18. Goswami M. , Jawali N. . ( 2010; ). N-Acetylcysteine-mediated modulation of bacterial antibiotic susceptibility. . Antimicrob Agents Chemother 54:, 3529–3530. [CrossRef] [PubMed]
    [Google Scholar]
  19. Goswami M. , Mangoli S. H. , Jawali N. . ( 2006; ). Involvement of reactive oxygen species in the action of ciprofloxacin against Escherichia coli . . Antimicrob Agents Chemother 50:, 949–954. [CrossRef] [PubMed]
    [Google Scholar]
  20. Goswami M. , Mangoli S. H. , Jawali N. . ( 2007; ). Effects of glutathione and ascorbic acid on streptomycin sensitivity of Escherichia coli . . Antimicrob Agents Chemother 51:, 1119–1122. [CrossRef] [PubMed]
    [Google Scholar]
  21. Hau T. . ( 1990; ). Bacteria, toxins, and the peritoneum. . World J Surg 14:, 167–175. [CrossRef] [PubMed]
    [Google Scholar]
  22. Herzog T. , Chromik A. M. , Uhl W. . ( 2010; ). Treatment of complicated intra-abdominal infections in the era of multi-drug resistant bacteria. . Eur J Med Res 15:, 525–532. [CrossRef] [PubMed]
    [Google Scholar]
  23. Hogg N. , Joseph J. , Kalyanaraman B. . ( 1994; ). The oxidation of α-tocopherol and trolox by peroxynitrite. . Arch Biochem Biophys 314:, 153–158. [CrossRef] [PubMed]
    [Google Scholar]
  24. Jiang Q. , Cross A. S. , Singh I. S. , Chen T. T. , Viscardi R. M. , Hasday J. D. . ( 2000; ). Febrile core temperature is essential for optimal host defense in bacterial peritonitis. . Infect Immun 68:, 1265–1270. [CrossRef] [PubMed]
    [Google Scholar]
  25. Joiner K. A. , Brown E. J. , Frank M. M. . ( 1984; ). Complement and bacteria: chemistry and biology in host defense. . Annu Rev Immunol 2:, 461–492. [CrossRef] [PubMed]
    [Google Scholar]
  26. Kadkhodaee M. , Khastar H. , Faghihi M. , Ghaznavi R. , Zahmatkesh M. . ( 2005; ). Effects of co-supplementation of vitamins E and C on gentamicin-induced nephrotoxicity in rat. . Exp Physiol 90:, 571–576. [CrossRef] [PubMed]
    [Google Scholar]
  27. Khan N. M. , Poduval T. B. . ( 2011; ). Immunomodulatory and immunotoxic effects of bilirubin: molecular mechanisms. . J Leukoc Biol 90:, 997–1015. [CrossRef] [PubMed]
    [Google Scholar]
  28. Kim Y. M. , Hong S. J. , Billiar T. R. , Simmons R. L. . ( 1996; ). Counterprotective effect of erythrocytes in experimental bacterial peritonitis is due to scavenging of nitric oxide and reactive oxygen intermediates. . Infect Immun 64:, 3074–3080.[PubMed]
    [Google Scholar]
  29. Kim J. M. , Kim H. , Kwon S. B. , Lee S. Y. , Chung S. C. , Jeong D. W. , Min B. M. . ( 2004; ). Intracellular glutathione status regulates mouse bone marrow monocyte-derived macrophage differentiation and phagocytic activity. . Biochem Biophys Res Commun 325:, 101–108. [CrossRef] [PubMed]
    [Google Scholar]
  30. Kohanski M. A. , Dwyer D. J. , Collins J. J. . ( 2010; ). How antibiotics kill bacteria: from targets to networks. . Nat Rev Microbiol 8:, 423–435. [CrossRef] [PubMed]
    [Google Scholar]
  31. Krogfelt K. A. , Bergmans H. , Klemm P. . ( 1990; ). Direct evidence that the FimH protein is the mannose-specific adhesin of Escherichia coli type 1 fimbriae. . Infect Immun 58:, 1995–1998.[PubMed]
    [Google Scholar]
  32. Lazarev V. N. , Borisenko G. G. , Shkarupeta M. M. , Demina I. A. , Serebryakova M. V. , Galyamina M. A. , Levitskiy S. A. , Govorun V. M. . ( 2010; ). The role of intracellular glutathione in the progression of Chlamydia trachomatis infection. . Free Radic Biol Med 49:, 1947–1955. [CrossRef] [PubMed]
    [Google Scholar]
  33. Lopez N. , Kobayashi L. , Coimbra R. . ( 2011; ). A comprehensive review of abdominal infections. . World J Emerg Surg 6:, 7. [CrossRef] [PubMed]
    [Google Scholar]
  34. Marathe S. A. , Kumar R. , Ajitkumar P. , Nagaraja V. , Chakravortty D. . ( 2013; ). Curcumin reduces the antimicrobial activity of ciprofloxacin against Salmonella typhimurium and Salmonella typhi . . J Antimicrob Chemother 68:, 139–152. [CrossRef] [PubMed]
    [Google Scholar]
  35. May A. K. , Gleason T. G. , Sawyer R. G. , Pruett T. L. . ( 2000; ). Contribution of Escherichia coli alpha-hemolysin to bacterial virulence and to intraperitoneal alterations in peritonitis. . Infect Immun 68:, 176–183. [CrossRef] [PubMed]
    [Google Scholar]
  36. McLean S. , Bowman L. A. , Sanguinetti G. , Read R. C. , Poole R. K. . ( 2010; ). Peroxynitrite toxicity in Escherichia coli K12 elicits expression of oxidative stress responses and protein nitration and nitrosylation. . J Biol Chem 285:, 20724–20731. [CrossRef] [PubMed]
    [Google Scholar]
  37. Miller R. A. , Britigan B. E. . ( 1997; ). Role of oxidants in microbial pathophysiology. . Clin Microbiol Rev 10:, 1–18.[PubMed]
    [Google Scholar]
  38. Mingeot-Leclercq M. P. , Tulkens P. M. . ( 1999; ). Aminoglycosides: nephrotoxicity. . Antimicrob Agents Chemother 43:, 1003–1012.[PubMed]
    [Google Scholar]
  39. Montravers P. , Mohler J. , Saint Julien L. , Carbon C. . ( 1997; ). Evidence of the proinflammatory role of Enterococcus faecalis in polymicrobial peritonitis in rats. . Infect Immun 65:, 144–149.[PubMed]
    [Google Scholar]
  40. Müller C. M. , Aberg A. , Straseviçiene J. , Emody L. , Uhlin B. E. , Balsalobre C. . ( 2009; ). Type 1 fimbriae, a colonization factor of uropathogenic Escherichia coli, are controlled by the metabolic sensor CRP-cAMP. . PLoS Pathog 5:, e1000303. [CrossRef] [PubMed]
    [Google Scholar]
  41. Nathan C. F. , Hibbs J. B. Jr . ( 1991; ). Role of nitric oxide synthesis in macrophage antimicrobial activity. . Curr Opin Immunol 3:, 65–70. [CrossRef] [PubMed]
    [Google Scholar]
  42. Nathan C. , Shiloh M. U. . ( 2000; ). Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. . Proc Natl Acad Sci U S A 97:, 8841–8848. [CrossRef] [PubMed]
    [Google Scholar]
  43. Pavlidis T. E. . ( 2003; ). Cellular changes in association with defense mechanisms in intra-abdominal sepsis. . Minerva Chir 58:, 777–781.[PubMed]
    [Google Scholar]
  44. Pomposiello P. J. , Demple B. . ( 2000; ). Oxidative stress. . In Encyclopedia of Microbiology, , 2nd edn., pp. 526–532. Edited by Lederberg J. . . San Diego, CA:: Academic Press;.
    [Google Scholar]
  45. Rocksén D. , Lilliehöök B. , Larsson R. , Johansson T. , Bucht A. . ( 2000; ). Differential anti-inflammatory and anti-oxidative effects of dexamethasone and N-acetylcysteine in endotoxin-induced lung inflammation. . Clin Exp Immunol 122:, 249–256.[PubMed] [CrossRef]
    [Google Scholar]
  46. Rooijakkers S. H. , van Strijp J. A. . ( 2007; ). Bacterial complement evasion. . Mol Immunol 44:, 23–32. [CrossRef] [PubMed]
    [Google Scholar]
  47. Sha S. H. , Schacht J. . ( 2000; ). Antioxidants attenuate gentamicin-induced free radical formation in vitro and ototoxicity in vivo: d-methionine is a potential protectant. . Hear Res 142:, 34–40. [CrossRef] [PubMed]
    [Google Scholar]
  48. Sharma D. , Eichelberg M. R. , Haag J. D. , Meilahn A. L. , Muelbl M. J. , Schell K. , Smits B. M. , Gould M. N. . ( 2012; ). Effective flow cytometric phenotyping of cells using minimal amounts of antibody. . Biotechniques 53:, 57–60.[PubMed]
    [Google Scholar]
  49. Steinhauser M. L. , Hogaboam C. M. , Matsukawa A. , Lukacs N. W. , Strieter R. M. , Kunkel S. L. . ( 2000; ). Chemokine C10 promotes disease resolution and survival in an experimental model of bacterial sepsis. . Infect Immun 68:, 6108–6114. [CrossRef] [PubMed]
    [Google Scholar]
  50. Sterns T. , Pollak N. , Echtenacher B. , Männel D. N. . ( 2005; ). Divergence of protection induced by bacterial products and sepsis-induced immune suppression. . Infect Immun 73:, 4905–4912. [CrossRef] [PubMed]
    [Google Scholar]
  51. Tajimi K. M. D., , Kosugi I. , Ohmura A. M. D. , Okada K. M. D. . ( 1982; ). Reduced glutathione significantly improves the survival rate in endotoxin shock. . Am Soc Anaesthesiol Abstr 57:, A130.[CrossRef]
    [Google Scholar]
  52. Tan X. X. , Actor J. K. , Chen Y. . ( 2005; ). Peptide nucleic acid antisense oligomer as a therapeutic strategy against bacterial infection: proof of principle using mouse intraperitoneal infection. . Antimicrob Agents Chemother 49:, 3203–3207. [CrossRef] [PubMed]
    [Google Scholar]
  53. Umezawa N. , Arakane K. , Ryu A. , Mashiko S. , Hirobe M. , Nagano T. . ( 1997; ). Participation of reactive oxygen species in phototoxicity induced by quinolone antibacterial agents. . Arch Biochem Biophys 342:, 275–281. [CrossRef] [PubMed]
    [Google Scholar]
  54. Walley K. R. , Lukacs N. W. , Standiford T. J. , Strieter R. M. , Kunkel S. L. . ( 1997; ). Elevated levels of macrophage inflammatory protein 2 in severe murine peritonitis increase neutrophil recruitment and mortality. . Infect Immun 65:, 3847–3851.[PubMed]
    [Google Scholar]
  55. Wentworth P. Jr , McDunn J. E. , Wentworth A. D. , Takeuchi C. , Nieva J. , Jones T. , Bautista C. , Ruedi J. M. , Gutierrez A. . & other authors ( 2002; ). Evidence for antibody-catalyzed ozone formation in bacterial killing and inflammation. . Science 298:, 2195–2199. [CrossRef] [PubMed]
    [Google Scholar]
  56. Wink D. A. , Kasprzak K. S. , Maragos C. M. , Elespuru R. K. , Misra M. , Dunams T. M. , Cebula T. A. , Koch W. H. , Andrews A. W. . & other authors ( 1991; ). DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. . Science 254:, 1001–1003. [CrossRef] [PubMed]
    [Google Scholar]
  57. Wu W. J. , Sha S. H. , Schacht J. . ( 2002; ). Recent advances in understanding aminoglycoside ototoxicity and its prevention. . Audiol Neurootol 7:, 171–174. [CrossRef] [PubMed]
    [Google Scholar]
  58. Yoda Y. , Nakazawa M. , Abe T. , Kawakami Z. . ( 1986; ). Prevention of doxorubicin myocardial toxicity in mice by reduced glutathione. . Cancer Res 46:, 2551–2556.[PubMed]
    [Google Scholar]
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