Introduction to Oxidative Stress

  • Mohinder Bansal
  • Naveen Kaushal


Oxygen as an essential element is critical for energy production and existence of all organisms on earth. However, there are potentially damaging effects also associated with it leading to production of oxygen centered free radicals. These radicals are highly reactive and can cause damage to various biomolecules. Presence of a physiological antioxidant defense system keeps these free radicals in check. Any imbalance in the levels of free radicals or reactive oxygen species (ROS) leads to oxidative stress in the body and may culminate in various patho-physiological conditions. In this chapter we have systematically provided details about the sources of free radicals, their types, their biomarkers and physiological significance.


Reactive Oxygen Species Nitric Oxide Reactive Oxygen Species Production Superoxide Radical Xanthine Oxidase 
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.


  1. Aikens J, Dix TA (1991) Perhydroxyl radical (Hoo.) initiated lipid peroxidation. The role of fatty acid hydroperoxides. J Biol Chem 266(23):15091–15098PubMedGoogle Scholar
  2. Albelda SM, Smith CW, Ward PA (1994) Adhesion molecules and inflammatory injury. FASEB J 8:504–512PubMedGoogle Scholar
  3. Albina JE, Reichner JS (1998) Role of nitric oxide in mediation of macrophage cytotoxicity and apoptosis. Cancer Metastasis Rev 17:39–53PubMedGoogle Scholar
  4. Babior B, Lambeth J, Nauseef W (2002) The neutrophil NADPH oxidase. Arch Biochem Biophys 397:342–344PubMedGoogle Scholar
  5. Banki K, Hutter E, Gonchoroff NJ, Perl A (1999) Elevation of mitochondrial transmembrane potential and reactive oxygen intermediate levels are early events and occur independently from activation of caspases in Fas signaling. J Immunol 162:1466–1479PubMedPubMedCentralGoogle Scholar
  6. Barnes P, Karin M (1997) Nuclear factor J B: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336:1066–1071PubMedGoogle Scholar
  7. Beckman K, Ames B (1997) Oxidative decay of DNA. J Biol Chem 272:19633–19636PubMedGoogle Scholar
  8. Beckman J, Koppenol W (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad and ugly. Am J Physiol 271:C1424–C1437PubMedGoogle Scholar
  9. Bergendi L, Benes L, Durackova Z, Ferencik M (1999) Chemistry, physiology and pathology of free radicals. Life Sci 65:1865–1874PubMedGoogle Scholar
  10. Berlett B, Stadtman E (1997) Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 272:20313–20316PubMedGoogle Scholar
  11. Bielski B, Cabelli D (1995) Superoxide and hydroxyl radical chemistry in aqueous solution. In: Foote C, Valentine J, Greenberg A, Liebman J (eds) Active oxygen in chemistry. Chapman & Hall, London, pp 66–104Google Scholar
  12. Bielski B, Cabelli B, Arudi R, Ross A (1985) Reactivity of Ro2/O2 radicals in aqueous solution. J Phys Chem Ref Data 14:1041–1100Google Scholar
  13. Bogdan C, Rollinghoff M, Diefenbach A (2000) Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Curr Opin Immunol 12:64–76PubMedGoogle Scholar
  14. Boveris A (1984) Determination of the production of superoxide radicals and hydrogen peroxide in mitochondria. Methods Enzymol 105:429–435PubMedGoogle Scholar
  15. Bredt D, Hwang P, Glatt C, Lowenstein C, Reed R, Synder S (1991) 450 reductase. Nature 351:714–718PubMedGoogle Scholar
  16. Brune B, Gotz C, Messmer UK, Sandau K, Hirvonen MR, Lapetina EG (1997) Superoxide formation and macrophage resistance to nitric oxide-mediated apoptosis. J Biol Chem 272:7253–7258PubMedGoogle Scholar
  17. Bruskov V, Malakhova L, Masalimov Z, Chernikov A (2002) Heat induced formation of reactive oxygen species and 8-oxoguanine, a biomarker of damage to DNA. Nucleic Acids Res 30:1354–1363PubMedPubMedCentralGoogle Scholar
  18. Bunn H, Poyton R (1996) Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev 76:839–885PubMedGoogle Scholar
  19. Butler AR, Glidewell C, Li MS (1988) Nitrosyl complexes of iron sulfur cluster. Adv Inorg Chem 32:335–392Google Scholar
  20. Carney JM, Starke-Reed PE, Oliver CN, Landum RW, Cheng MS et al (1991) Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-α phenylnitrone. Proc Natl Acad Sci U S A 88:3633–3636PubMedPubMedCentralGoogle Scholar
  21. Carr A, Mccall MR, Frei B (2000) Oxidation of LDL by myeloperoxidase and reactive nitrogen species-reaction pathways and antioxidant protection. Arterioscler Thromb Vasc Biol 20:1716–1723PubMedGoogle Scholar
  22. Castedo M, Hirsch T, Susin SA, Zamzami N, Marchetti P, Macho A, Kroemer G (1996) Sequential acquisition of mitochondrial and plasma membrane alterations during early lymphocyte apoptosis. J Immunol 157:512–521PubMedGoogle Scholar
  23. Castro L, Rodriguez M, Radi R (1994) Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide. J Biol Chem 269:29409–29415PubMedGoogle Scholar
  24. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–605PubMedGoogle Scholar
  25. Coles B, Ketterer B (1990) The role of glutathione and glutathione transferases in chemical carcinogenesis. Crit Rev Biochem Mol Biol 25:47–70PubMedGoogle Scholar
  26. Czapski G, Goldstein S (1995) The role of the reactions of no with superoxide and oxygen in biological systems: a kinetic approach. Free Radic Biol Med 19:785–794PubMedGoogle Scholar
  27. Darley-Usmar V, Wiseman H, Halliwell B (1995) Nitric oxide and oxygen radicals: a question of balance. FEBS Lett 369:131–135PubMedGoogle Scholar
  28. Davidson CA, Kaminski PM, Wolin MS (1997) Am J Physiol 273:L437–L444PubMedGoogle Scholar
  29. Davis K (1987) Protein damage and degradation by oxygen radicals. I. General aspects. J Biol Chem 262:9895–9901Google Scholar
  30. De Grey AD (2002) HO2*: the forgotten radical. DNA Cell Biol 21(4):251–257PubMedGoogle Scholar
  31. De Vos K, Goossens V, Boone E, Vercammen D, Vancompernolle K, Vandenabeele P, Haegeman G, Fiers W, Grooten J (1998) The 55-Kda tumor necrosis factor receptor induces clustering of mitochondria through its membrane-proximal region. J Biol Chem 273:9673–9680PubMedGoogle Scholar
  32. Decuyper-Debergh D, Piette J, Van De Vorst A (1987) Singlet oxygen-induced mutations in M13 lacZ phage DNA. EMBO J 6(10):3155–3161PubMedPubMedCentralGoogle Scholar
  33. Demple B, Amabile-Cuevas CF (1991) Redox redux: the control of oxidative stress response. Cell 67:837–840PubMedGoogle Scholar
  34. Di Mascio P, Bechara E, Medeiros M, Briviba K, Sies H (1994) Singlet molecular oxygen production in the reaction of peroxynitrite with hydrogen peroxide. FEBS Lett 355(3):287–289PubMedGoogle Scholar
  35. Di Mascio P, Briviba K, Sasaki S, Catalani L, Medeiros M, Bechara E, Sies H (1997) The reaction of peroxynitrite with tert-butyl hydroperoxide produces singlet molecular oxygen. Biol Chem 378(9):1071–1074PubMedGoogle Scholar
  36. Dröge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95PubMedGoogle Scholar
  37. Dumont A, Hehner S, Hofmann T, Ueffing M, Dro¨ Ge W, Schmitz M (1999) Hydrogen peroxide-induced apoptosis is CD95-independent, requires the release of mitochondria-derived reactive oxygen species and the activation of NF-Kb. Oncogene 18:747–757PubMedGoogle Scholar
  38. Enomoto A, Itoh K, Nagayoshie, Haruta J, Kimura T, Harada T, O’connort T, Yamamoto M (2001) High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of Are regulated drug metabolizing enzymes and antioxidant genes. Toxicol Sci 59:169–177PubMedGoogle Scholar
  39. Epe B, Ballmaier D, Roussyn I, Briviba K, Sies H (1996) DNA damage by peroxynitrite characterized with DNA repair enzymes. Nucleic Acids Res 24(21):4105–4110PubMedPubMedCentralGoogle Scholar
  40. Esteve J, Mompo J, De La Asuncion J, Sastre J, Asensi M, Boix J, Vina J, Vina J, Pallardo’ F (1999) Oxidative damage to mitochondrial DNA and glutathione oxidation in apoptosis: studies in vivo and in vitro. FASEB J 13:1055–1064PubMedGoogle Scholar
  41. Fandrey J, Frede S, Jelkmann W (1994) Role of hydrogen peroxide in hypoxia-induced erythropoietin production. Biochem J 303:507–510PubMedPubMedCentralGoogle Scholar
  42. Fang YZ, Yang S, Wu G (2002) Free radicals, antioxidants, and nutrition. Nutrition 18:872–879PubMedGoogle Scholar
  43. Faraci FM, Didion SP (2004) Superoxide dismutase isoforms in the vessel wall. Arterioscler Thromb Vasc Biol 24:1367PubMedGoogle Scholar
  44. Floyd R (1991) Oxidative damage to behavior during aging. Science 254:1597–97PubMedGoogle Scholar
  45. Forman H, Torres M (2001) Redox signaling in macrophages. Mol Aspects Med 22(4–5):189–216PubMedGoogle Scholar
  46. Frenette PS, Wagner DD (1996) Adhesion molecules. Part I. N Engl J Med 334:1526–1529PubMedGoogle Scholar
  47. Garrison W (1987) Reaction mechanisms in the radiolysis of peptides, polypeptides, and proteins. Chem Rev 87:381–398Google Scholar
  48. Gedik CM, Boyle SP, Wood SG, Vaughan NJ, Collins AR (2002) Oxidative stress in humans: validation of biomarkers of DNA damage. Carcinogenesis 23:1441–1446PubMedGoogle Scholar
  49. Ghafourifar P, Cadenas E (2005) Mitochondrial nitric oxide synthase. Trends Pharmacol Sci 26:190–195PubMedGoogle Scholar
  50. Gopaul NK, Halliwell B, Anggård EE (2000) Measurement of plasma F2-isoprostanes as an index of lipid peroxidation does not appear to be confounded by diet. Free Radic Res 33(2):115–127PubMedGoogle Scholar
  51. Gottschling B, Maronpot R, Hailey J, Peddada S, Moomaw C, Klaunig J, Nyska A (2001) The role of oxidative stress in indium phosphide-induced lung carcinogenesis in rats. Toxicol Sci 64:28–40PubMedGoogle Scholar
  52. Griendling KK, Sorescu D, Lasse’Gue B, Ushio-Fukai M (2000) Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol 20:2175–2183PubMedGoogle Scholar
  53. Griffiths HR, Moller L, Bartosz G, Bast A, Bertonni-Freddari C, Collins A, Coolen S, Haenen G, Hoberg AM, Loft S, Lunec J, Olinski R, Parry J, Pompella A, Poulsen H, Verhagen H, Astley SB (2002) Biomarkers. Mol Aspects Med 23:101–209PubMedGoogle Scholar
  54. Guzik TJ, Mussa S, Gastaldi D, Sadowski J, Ratnatunga C, Pillai R, Channon KM (2002) Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 105:1656–1662PubMedGoogle Scholar
  55. Haber F, Weiss J (1934) The catalytic decomposition of hydrogen peroxide by iron salts. Proc R Soc Lond Ser A 147:332–351Google Scholar
  56. Halliwell B (2000) Lipid peroxidation, antioxidants and cardiovascular disease: how should we move forward? Cardiovasc Res 47(3):410–418PubMedGoogle Scholar
  57. Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97(6):1634–1658PubMedGoogle Scholar
  58. Halliwell B (2009) The wanderings of a free radical. Free Radic Biol Med 46:531–542PubMedGoogle Scholar
  59. Halliwell B, Gutterdgem (1999) Free radicals in biology and medicine, 3rd edn. Oxford University Press, Midsomer NortonGoogle Scholar
  60. Halliwell B, Whiteman M (2004) Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 142:231–255PubMedPubMedCentralGoogle Scholar
  61. Halliwell B, Clement M, Long L (2000) Hydrogen peroxide in the human body. FEBS Lett 486:10–13PubMedGoogle Scholar
  62. Hamuro J, Murata Y, Suzuki M, Takatsuki F, Suga T (1999) The triggering and healing of tumor stromal inflammatory reactions regulated by oxidative and reductive macrophages. Gann Monogr Cancer Res 48:153–164Google Scholar
  63. Hauptmann N, Cadenas E (1997) The oxygen paradox: biochemistry of active oxygen. In: Oxidative stress and the molecular biology of antioxidant defenses. Csh monographs vol 34. Cold Spring Harbor Laboratory Press, PlainviewGoogle Scholar
  64. Hawkins C, Brown B, Davies M (2001) Hypochlorite- and hypochlorite-mediate D radical formation and its role in cell lysis. Arch Biochem Biophys 395:137–145PubMedGoogle Scholar
  65. Henderson C, Mclaren A, Moffat G, Bacon E, Wolf C (1998) Pi-class glutathione S-transferase: regulation and function. Chem Biol Interact 111–112:69–82PubMedGoogle Scholar
  66. Hennet T, Richter C, Peterhans E (1993) Tumor necrosis factor-a induces superoxide anion generation in mitochondria of L929 cells. Biochem J 289:587–592PubMedPubMedCentralGoogle Scholar
  67. Henry Y, Lepoivre M, Drapier J, Ducrocq C, Boucher J, Guissani A (1993) Epr characterization of molecular targets for NO in mammalian cells and organelles. FASEB J 7:1124–1134PubMedGoogle Scholar
  68. Hockenbery D, Oltvai Z, Yin X, Milliman C, Korsmeyer S (1993) Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75:241–251PubMedGoogle Scholar
  69. Huang L, Arany Z, Livingston D, And Bunn F (1996) Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit. J Biol Chem 271:32253–32259PubMedGoogle Scholar
  70. Huang L, Gu J, Schau M, Bunn H (1998) Regulation of hypoxia-inducible factor 1a is mediated by it oxygen-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A 95:7987–7992PubMedPubMedCentralGoogle Scholar
  71. Hug H, Enari M, Nagata S (1994) No requirement of reactive oxygen intermediates in Fas-mediated apoptosis. FEBS Lett 351:311–313PubMedGoogle Scholar
  72. Hur G, Ryu Y, Yun H, Jeon B, Kim Y, Seok J, Lee J (1999) Hepatic ischemia/reperfusion in rats induces iNOS gene transcription by activation of NF-kappaB. Biochem Biophys Res Commun 261:917–922PubMedGoogle Scholar
  73. Ignarro LJ, Kadowitz PJ (1985) The pharmacological and physiological role of cyclic GMP in vascular smooth muscle relaxation. Ann Pharmacol Toxicol 25:171–191Google Scholar
  74. Iida T, Furuta A, Kawashima M, Nishida J, Nakabeppu Y, Iwaki T (2001) Accumulation of 8-Oxo-2-deoxyguanosine and increased expression of Hmth1 protein in brain tumors. Neuro-Oncol 3:73–81PubMedPubMedCentralGoogle Scholar
  75. Immenschuh S, Ramadorig (2000) Gene regulation of heme oxygenase-1 as a therapeutic target. Biochem Pharmacol 60:1121–1128PubMedGoogle Scholar
  76. Jacobson M, Burne J, Raff M (1994) Programmed cell death and Bcl-2 protection in the absence of a nucleus. EMBO J 13:1899–1910PubMedPubMedCentralGoogle Scholar
  77. Janssen Y, Van Houten B, Borm P, Mossman B (1993) Cell and tissue responses to oxidative damage. Lab Invest 69:261–274PubMedGoogle Scholar
  78. Jeong J, Juedes M, Wogan G (1998) Mutations induced in the supF gene of pSP189 by hydroxyl radical and singlet oxygen: relevance to peroxynitrite mutagenesis. Chem Res Toxicol 11(5):550–556PubMedGoogle Scholar
  79. Johnson T, Yu Z, Ferrans V, Lowenstein R, Finkel T (1996) Reactive oxygen species are downstream mediators of P53-dependent apoptosis. Proc Natl Acad Sci U S A 93:11848–11852PubMedPubMedCentralGoogle Scholar
  80. Jones DP (2002) Redox potential of GSH/GSSG couple: assay and biological significance. Methods Enzymol 348:93–112PubMedGoogle Scholar
  81. Jones D (2008) Radical-free biology of oxidative stress. Am J Physiol Cell Physiol 295(4):C849–C868, Epub 2008 Aug 6PubMedPubMedCentralGoogle Scholar
  82. Jones SA, O’donnell VB, Wood JD, Broughton JP, Hughes EJ, Jones OT (1996) Expression of phagocyte NADPH oxidase components in human endothelial cells. Am J Physiol Heart Circ Physiol 271:H1626–H1634Google Scholar
  83. Joseph J, Cutler R (1994) The role of oxidative stress in signal transduction changes and cell loss in senescence. Ann N Y Acad Sci 738:37PubMedGoogle Scholar
  84. Jungermann K, Kietzmann T (1997) Role of oxygen in the zonation of carbohydrate metabolism and gene expression in liver. Kidney Int 51:402–412PubMedGoogle Scholar
  85. Kanofsky J (1989) Singlet oxygen production by biological systems. Chem Biol Interact 70(1–2):1–28PubMedGoogle Scholar
  86. Keisari Y, Braun L, Flescher E (1983) The oxidative burst and related phenomena in mouse macrophages elicited by different sterile inflammatory stimuli. Immunobiology 165:78–89PubMedGoogle Scholar
  87. Kilhovd B, Juutilainen A, Lehto S, Rönnemaa T, Torjesen P, Hanssen K, Laakso M (2007) Increased serum levels of advanced glycation end products predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study. Diabetologia 50(7):1409–1417, Epub 2007 May 4PubMedGoogle Scholar
  88. Klatt P, Lamas S (2000) Regulation of protein function by s glutathiolation in response to oxidative and nitrosative stress. Eur J Biochem 267:4928–4944PubMedGoogle Scholar
  89. Klebanoff S, Vadas M, Harlan J, Sparks L, Gamble J, Agosti J, Waltersdorph A (1986) Stimulation of neutrophils by tumor necrosis factor. J Immunol 136:4220–4225PubMedGoogle Scholar
  90. Klotz Lo, Briviba K, Sies H (2000) Signalling by singlet oxygen in biological systems. Section: reactive species as intracellular messengers. Chapter 1. In: Chandan KS, Helmut S, Bauerle PA (eds) Antioxidant and redox regulations of genes. Academic Press, San DiegoGoogle Scholar
  91. Knight T, Kurtz A, Bajt M, Hinson J, Jaeschke H (2001) Vascular and hepatocellular peroxynitrite formation during acetaminophen toxicity: role of mitochondria L oxidant stress. Toxicol Sci 62:212–220PubMedGoogle Scholar
  92. Kohen R, Nyska A (2002) Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Pathol 30(6):620–650PubMedGoogle Scholar
  93. Korsmeyer S (1995) Regulators of cell death. Trends Genet 11:101–105PubMedGoogle Scholar
  94. Lamas S, Marsden P, Li G, Tempst P, Michel T (1992) Endothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform. Proc Natl Acad Sci U S A 89:6348–6352PubMedPubMedCentralGoogle Scholar
  95. Lands WEM et al (1984) In: Pryor W (ed) Free radicals in biology, vol 6. Academic, New York, pp 39–61Google Scholar
  96. Levine R, Stadtman E (2001) Oxidative modification of proteins during aging. Exp Gerontol 36:1495–1502PubMedGoogle Scholar
  97. Liochev SI, Fridovich I (2002) The Haber–Weiss cycle—70 years later: an alternative view. Redox Rep 7:55–57PubMedGoogle Scholar
  98. Liu Y, Zhu B, Luo L, Li P, Paty D, Cynader M (2001) Heme oxygenase-1 plays an important protective role in experimental autoimmune encephalomyelitis. Neuroreport 12:1841–1845PubMedGoogle Scholar
  99. Lo’Pez-Barneo J, Pardal R, Montoro R, Smani T, Garcı’A-Hirschfeld J, Urena J (1999) K1 and Ca21 channel activity and cytosolic [Ca21] in oxygen-sensing tissues. Respir Physiol 115:215–227Google Scholar
  100. Los M, Droge W, Stricker K, Baeuerle PA, Schulze-Osthoff K (1995) Hydrogen peroxide as a potent activator of T lymphocyte functions. Eur J Immunol 25:159–165PubMedGoogle Scholar
  101. Mckersie BD Oxidative stress by, University Of Guelph (Posted on the internet in 1996)Google Scholar
  102. Mehta JL, Rasouli N, Sinha AK, Molavi B (2006) Oxidative stress in diabetes: a mechanistic overview of its effects on atherogenesis and myocardial dysfunction. Int J Biochem Cell Biol 38:794–803PubMedGoogle Scholar
  103. Meier B, Radeke H, Selle S, Younes M, Sies H, Resch K, Habermehl G (1989) Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumor necrosis factor-a. Biochem J 263:539–545PubMedPubMedCentralGoogle Scholar
  104. Mendez JI, Nicholson WJ, Taylor WR (2005) Sod isoforms and signaling in blood vessels: evidence for the importance of Ros compartmentalization. Arterioscler Thromb Vasc Biol 25:887–888PubMedGoogle Scholar
  105. Milne G, Musiek E, Morrow J (2005) F2-isoprostanes as markers of oxidative stress in vivo: an overview. Biomarkers 10(Suppl 1):S10–S23PubMedGoogle Scholar
  106. Miyata T, Maeda K, Kurokawa K, Van Ypersele De Strihou C (1997) Oxidation conspires with glycation to generate noxious advanced glycation end products in renal failure. Nephrol Dial Transplant 12:255–258PubMedGoogle Scholar
  107. Mohora M, Greabu M, Muscurel C, Duţă C, Totan A (2007) The sources and the targets of oxidative stress in the etiology of diabetic complications. Romanian J Biophys 17(2):63–84, BucharestGoogle Scholar
  108. Moncada S, Higgs A (1993) The L-arginine-nitric oxide pathway. N Engl J Med 329:2002–2012PubMedGoogle Scholar
  109. Montuschi P, Barnes P, Roberts L 2nd (2004) Isoprostanes: markers and mediators of oxidative stress. FASEB J 18(15):1791–1800PubMedGoogle Scholar
  110. Murphy M, Packer M, Scarlet J, Martin S (1998) Peroxynitrite: a biologically significant oxidant. Gen Pharmacol 31:179–186PubMedGoogle Scholar
  111. Neumcke I, Schneider B, Fandrey J, Pagel H (1999) Effects of pro and antioxidative compounds on renal production of erythropoietin. Endocrinology 140:641–645PubMedGoogle Scholar
  112. O’donnell V, Spycher S, Azzi A (1995) Involvement of oxidants and oxidant-generating enzyme(S) in tumor necrosis factor-a-mediated apoptosis: role for lipoxygenase pathway but not mitochondrial respiratory chain. Biochem J 310:133–141PubMedPubMedCentralGoogle Scholar
  113. Ohshima H, Sawa T, Akaike T (2006) 8-nitroguanine, a product of nitrative DNA damage caused by reactive nitrogen species: formation, occurrence, and implications in inflammation and carcinogenesis. Antioxid Redox Signal 8(5–6):1033–1045PubMedGoogle Scholar
  114. Pastor N, Weinstein H, Jamison E, Brenowitz M (2000) A detailed interpretation of OH radical footprints in a TBP-DNA complex reveals the role of dynamics in the mechanism of sequence-specific binding. J Mol Biol 304(1):55–68PubMedGoogle Scholar
  115. Patel R, Mollering D, Murphy-Ullrich J, Jo H, Beckman J, Darley-Usmar V (2000) Cell signaling by reactive nitrogen and oxygen species in atherosclerosis. Free Radic Biol Med 28:1780–1794PubMedGoogle Scholar
  116. Piette J (1991) Biological consequences associated with DNA oxidation mediated by singlet oxygen. J Photochem Photobiol B 11(3–4):241–260PubMedGoogle Scholar
  117. Poss W, Huecksteadt T, Panus P, Freeman B, Hoidal J (1996) Regulation of xanthine dehydrogenase and xanthine oxidase activity by hypoxia. Am J Physiol Lung Cell Mol Physiol 270:L941–L946Google Scholar
  118. Preiser J-C (2012) Oxidative stress. J Parenter Enter Nutr 36(2):147–154Google Scholar
  119. Richter C, Gogvadze V, Laffranchi R, Schlapbach R, Schwezer M, Suter M, Walter P (1995) Oxidants in mitochondria: from physiology to diseases. Biochim Biophys Acta 1271:67–74PubMedGoogle Scholar
  120. Ridnour LA, Thomas DD, Mancardi D, Espey MG, Miranda KM, Paolocci N et al (2004) The chemistry of nitrosative stress induced by nitric oxide and reactive nitrogen oxide species. Putting perspective on stressful biological situations. Biol Chem 385:1–10PubMedGoogle Scholar
  121. Saran M, Bors W (1989) Oxygen radicals acting as chemical messengers: a hypothesis. Free Rad Res Commun 7:3–6Google Scholar
  122. Schafer F, Buettnergr (2001) Redox environments of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Rad Biol Med 30:1191–1212PubMedGoogle Scholar
  123. Schaller MD, Borgman CA, Cobb BS, Vines RR, Reynolds AB, Parsons JT (1992) Pp125fak a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A 89:5192–5196PubMedPubMedCentralGoogle Scholar
  124. Schulze-Osthoff K, Bakker A, Vanhaesebroeck B, Beyaert R, Jacob W, And Fiers W (1992) Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation. J Biol Chem 267:5317–5323PubMedGoogle Scholar
  125. Semenza G (2000) Hif-1: mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol 88:1474–1480PubMedGoogle Scholar
  126. Sen CK (2000) Cellular thiols and redox-regulated signal transduction. Curr Top Cell Regul 36:1–30PubMedGoogle Scholar
  127. Shacter E (2000) Quantification and significance of protein oxidation in biological samples. Drug Metab Rev 32(3–4):307–326PubMedGoogle Scholar
  128. Shalaby M, Aggarwal B, Rinderknecht E, Svedersky L, Finkle B, Palladino M Jr (1985) Activation of human polymorphonuclear neutrophil functions by interferon-G and tumor necrosis factor. J Immunol 135:2069–2073PubMedGoogle Scholar
  129. Slater A, Stefan C, Novel I, Van Den Dobbelsteen D, Orrenius S (1995) Signalling mechanisms and oxidative stress in apoptosis. Toxicol Lett 82–83:149–153PubMedGoogle Scholar
  130. Sohal R, Allen R (1990) Oxidative stress as a causal factor in differentiation and aging: a unifying hypothesis. Exp Gerontol 25:499–522PubMedGoogle Scholar
  131. Steinbeck MJ, Khan AU, Karnovsky MJ (1992) Intracellular singlet oxygen generation by phagocytosing neutrophils in response to particles coated with a chemical trap. J Biol Chem 267(19):13425–13433PubMedGoogle Scholar
  132. Steinbeck MJ, Khan AU, Karnovsky MJ (1993) Extracellular production of singlet oxygen by stimulated macrophages quantified using 9,10-diphenylanthracene and perylene in a polystyrene film. J Biol Chem 268(21):15649–15654PubMedGoogle Scholar
  133. Takahashi S, Hirose M, Tamano S, Ozaki M, Orita S, Ito T, Takeuchi M, Ochi H, Fukada S, Kasai H, Shirai T (1998) Immunohistochemical detection of 8-hydroxy-2-deoxyguanosinE in paraffin embedded sections of rat liver after carbon tetrachloride treatment. Toxicol Pathol 26:247–252PubMedGoogle Scholar
  134. Thannickal VJ, Fanburg BL (1995) Activation of an H2O2-generating NADH oxidase in human lung fibroblasts by transforming growth factor beta 1. J Biol Chem 270:30334–30338PubMedGoogle Scholar
  135. Townsend DM, Tew KD, Tapiero H (2003) The importance of glutathione in human disease. Biomed Pharmacother 57:145–155PubMedGoogle Scholar
  136. Um H, Orenstein J, Wahl S (1996) Fas mediates apoptosis in human monocytes by a reactive oxygen intermediate dependent pathway. J Immunol 156:3469–3477PubMedGoogle Scholar
  137. Upham B, Wagner J (2001) Toxicant-induced oxidative stress in cancer. Toxicol Sci 64:1–3PubMedGoogle Scholar
  138. Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40PubMedGoogle Scholar
  139. Valko M, Leibfritz D, Moncol J, Mark TD, Cronin C, Milan M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84PubMedGoogle Scholar
  140. Vincent J, Zhang H, Szabo C, Preiser J (2000) Effects of nitric oxide in septic shock. Am J Respir Crit Care Med 161:1781–1785PubMedGoogle Scholar
  141. Von Sonntag C (1987) The chemical basis of radiation biology. Taylor & Francis, LondonGoogle Scholar
  142. Wang G, Jiang B, Rue E, Semenza G (1995) Hypoxia-inducible factor 1 is a basic helix-loop-helix-Pas heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A 92:5510–5514PubMedPubMedCentralGoogle Scholar
  143. Weinstein D, Mihm M, Bauer J (2000) Cardiac peroxynitrite formation and left ventricular dysfunction following doxorubicin treatment in mice. J Pharmacol Exp Ther 294:396–401PubMedGoogle Scholar
  144. Williams M, Henkart P (1996) Role of reactive oxygen intermediates in Tcr-induced death of T cell blasts and hybridomas. J Immunol 157:2395–2402PubMedGoogle Scholar
  145. Wolin MS, Burke-Wolin TM, Mohazzab-H KM (1999) Roles of NADPH oxidases and reactive oxygen species in vascular oxygen sensing mechanisms. Respir Physiol 115:229–238PubMedGoogle Scholar
  146. Wu J (1993) Advanced glycosylation end products: a new disease marker for diabetes and aging. J Clin Lab Anal 7(5):252–255PubMedGoogle Scholar
  147. Wyllie A, Kerr J, Currie A (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306PubMedGoogle Scholar
  148. Xie Q, Cho H, Calaycay J, Mumford R, Swiderek K, Lee T, Ding A, Troso T, Nathan C (1992) Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256:225–228PubMedGoogle Scholar
  149. Zamzami Marchetti N, Marchetti P, Castedo M, Decaudin D, Macho A, Hirsch T, Susin S, Petit P, Mignotte B, Kroemer G (1995) Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J Exp Med 182:367–377Google Scholar
  150. Zhu H, Bunn H (1999) Oxygen sensing and signaling: impact on the regulation of physiologically important genes. Respir Physiol 115:239–247PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer India 2014

Authors and Affiliations

  • Mohinder Bansal
    • 1
  • Naveen Kaushal
    • 1
  1. 1.Department of BiophysicsPanjab UniversityChandigarhIndia

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