Skip to main content

Biomarkers of Oxidative Stress in Blood

  • Living reference work entry
  • First Online:
General Methods in Biomarker Research and their Applications

Abstract

The malfunction of the finely tuned homeostatic systems that maintain oxidative balance is part of the pathology of almost every known human disease. There are scores of individual components and pathways which maintain oxidative balance. One or more of these maybe altered in disease, though it is difficult to determine what the triggering pathway or analyte is. In light of this, biomarkers are useful tools to evaluate oxidative imbalance or indicate the degree of oxidative stress.

When selecting which biomarkers for oxidative stress, there are three categories of biomarkers to choose from. These depend on the target of oxidation and are isoprostanes, oxysterols, and hydroxyoctadecadienoic acid. Biomarkers of nucleic acid oxidation include nucleotides, single- and double-stranded breaks in DNA, and RNA oxidative products. Oxidative damage to proteins can be measured via protein carbonyls, glutathione levels, glycosylated hemoglobin, and erythrocyte oxidation from fluorescent heme degradation products. In isolation, each of these will give specific information on the target of oxidation, as well as providing tentative information regarding affected pathways. Here, we describe in detail the selective markers, protein carbonyls, oxysterols, isoprostanes, heme degradation products, HbA1C, and many more.

All the above biomarkers are discussed in this review. As with ideal biomarkers, these have a mixed utility and can be measured in different tissues and compartments. In blood, each will provide a certain amount of information, which will vary between giving a systemic scope of oxidative stress (e.g., erythrocyte oxidation) to evaluating oxidative stress in specific diseases (e.g., glycosylated hemoglobin and diabetes). Ideally, it is better to select multiple biomarkers based on an in-depth knowledge of the condition at hand.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

Similar content being viewed by others

Abbreviations

8-OHG:

7,8-Dihydro-8-Oxo-Guanosine

8-oxodG:

8-Oxo-7 8-Dihydro-2′Deoxyguanosine

8-oxoGua:

8-Oxo-7 8-Dihydroguanine

AGE:

Advanced Glycation End Products

AO:

Antioxidant

ATP:

Adenosine Triphosphate

CRP:

C-Reactive Protein

DNA:

Deoxyribonucleic Acid

DSB:

Double-Stranded Break

ELISA:

Enzyme-Linked Immunosorbent Assay

FACS:

Fluorescence Activated Cell Sorting

GC:

Gas Chromatography

GSH:

Glutathione

HbA1c:

Glycosylated Hemoglobin

HPLC:

High Performance Liquid Chromatography

IFNγ:

Interferon γ

IHC:

Immunohistochemistry

IL-1:

Interleukin-1

IL-6:

Interleukin-6

mRNA:

Messenger Ribonucleic Acid

MS:

Mass Spectrometry

NF-κB:

Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells

PBMC:

Peripheral Blood Mononuclear Cells

RAGE:

Receptors for Advanced Glycation End Products

RNA:

Ribonucleic Acid

ROS:

Reactive Oxygen Species

SSB:

Single-Stranded Break

TNFα:

Tumor Necrosis Factor α

References

  • Abe T, Isobe C, Murata T, Sato C, Tohgi H. Alteration of 8-hydroxyguanosine concentrations in the cerebrospinal fluid and serum from patients with Parkinson’s disease. Neurosci Lett. 2003;336(2):105–8.

    Article  CAS  PubMed  Google Scholar 

  • Aghaloo TL, Amantea CM, Cowan CM, Richardson JA, Wu BM, Parhami F, Tetradis S. Oxysterols enhance osteoblast differentiation in vitro and bone healing in vivo. J Orthop Res. 2007;25(11):1488–97.

    Article  CAS  PubMed  Google Scholar 

  • Ames BN, Shigenaga MK, Gold LS. DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis. Environ Health Perspect. 1993;101 Suppl 5:35–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bachi A, Zuccato E, Baraldi M, Fanelli R, Chiabrando C. Measurement of urinary 8-Epi-prostaglandin F2alpha, a novel index of lipid peroxidation in vivo, by immunoaffinity extraction/gas chromatography-mass spectrometry. Basal levels in smokers and nonsmokers. Free Radic Biol Med. 1996;20(4):619–24.

    Article  CAS  PubMed  Google Scholar 

  • Badr KF, Abi-Antoun TE. Isoprostanes and the kidney. Antioxid Redox Signal. 2005;7(1–2):236–43.

    Article  CAS  PubMed  Google Scholar 

  • Bandeen-Roche K, Walston JD, Huang Y, Semba RD, Ferrucci L. Measuring systemic inflammatory regulation in older adults: evidence and utility. Rejuvenation Res. 2009;12(6):403–10.

    Article  PubMed Central  PubMed  Google Scholar 

  • Beutler E, Gelbart T. Plasma glutathione in health and in patients with malignant disease. J Lab Clin Med. 1985;105(5):581–4.

    CAS  PubMed  Google Scholar 

  • Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95.

    Article  Google Scholar 

  • Bonaventura C, Henkens R, Alayash AI, Banerjee S, Crumbliss AL. Molecular controls of the oxygenation and redox reactions of hemoglobin. Antioxid Redox Signal. 2013;18(17):2298–313.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bopp C, Bierhaus A, Hofer S, Bouchon A, Nawroth PP, Martin E, Weigand MA. Bench-to-bedside review: the inflammation-perpetuating pattern-recognition receptor RAGE as a therapeutic target in sepsis. Crit Care. 2008;12(1):201.

    Article  PubMed Central  PubMed  Google Scholar 

  • Broedbaek K, Poulsen HE, Weimann A, Kom GD, Schwedhelm E, Nielsen P, Boger RH. Urinary excretion of biomarkers of oxidatively damaged DNA and RNA in hereditary hemochromatosis. Free Radic Biol Med. 2009;47(8):1230–3.

    Article  CAS  PubMed  Google Scholar 

  • Broedbaek K, Ribel-Madsen R, Henriksen T, Weimann A, Petersen M, Andersen JT, Afzal S, Hjelvang B, Roberts 2nd LJ, Vaag A, Poulsen P, Poulsen HE. Genetic and environmental influences on oxidative damage assessed in elderly Danish twins. Free Radic Biol Med. 2011a;50(11):1488–91.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Broedbaek K, Siersma V, Andersen JT, Petersen M, Afzal S, Hjelvang B, Weimann A, Semba RD, Ferrucci L, Poulsen HE. The association between low-grade inflammation, iron status and nucleic acid oxidation in the elderly. Free Radic Res. 2011b;45(4):409–16.

    Article  CAS  PubMed  Google Scholar 

  • Cade WT. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther. 2008;88(11):1322–35.

    Article  PubMed Central  PubMed  Google Scholar 

  • Chapple IL. Reactive oxygen species and antioxidants in inflammatory diseases. J Clin Periodontol. 1997;24(5):287–96.

    Article  CAS  PubMed  Google Scholar 

  • Collins AR. The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol. 2004;26(3):249–61.

    Article  CAS  PubMed  Google Scholar 

  • Collins, et al. Mol Biotechnol. 2004;26:249–61.

    Article  CAS  PubMed  Google Scholar 

  • Costa AD, Pierre SV, Cohen MV, Downey JM, Garlid KD. cGMP signalling in pre- and post-conditioning: the role of mitochondria. Cardiovasc Res. 2008;77(2):344–52.

    Article  CAS  PubMed  Google Scholar 

  • Crawford JH, Chacko BK, Kevil CG, Patel RP. The red blood cell and vascular function in health and disease. Antioxid Redox Signal. 2004;6(6):992–9.

    Article  CAS  PubMed  Google Scholar 

  • Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta. 2003;329(1–2):23–38.

    Article  CAS  PubMed  Google Scholar 

  • Dar ME, Jorgensen TJ. Deletions at short direct repeats and base substitutions are characteristic mutations for bleomycin-induced double- and single-strand breaks, respectively, in a human shuttle vector system. Nucleic Acids Res. 1995;23(16):3224–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dzeletovic S, Breuer O, Lund E, Diczfalusy U. Determination of cholesterol oxidation products in human plasma by isotope dilution-mass spectrometry. Anal Biochem. 1995;225(1):73–80.

    Article  CAS  PubMed  Google Scholar 

  • Encode Project Consortium, Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE, Kuehn MS, Taylor CM, Neph S, Koch CM, Asthana S, Malhotra A, Adzhubei I, Greenbaum JA, Andrews RM, Flicek P, Boyle PJ, Cao H, Carter NP, Clelland GK, Davis S, Day N, Dhami P, Dillon SC, Dorschner MO, Fiegler H, Giresi PG, Goldy J, Hawrylycz M, Haydock A, Humbert R, James KD, Johnson BE, Johnson EM, Frum TT, Rosenzweig ER, Karnani N, Lee K, Lefebvre GC, Navas PA, Neri F, Parker SC, Sabo PJ, Sandstrom R, Shafer A, Vetrie D, Weaver M, Wilcox S, Yu M, Collins FS, Dekker J, Lieb JD, Tullius TD, Crawford GE, Sunyaev S, Noble WS, Dunham I, Denoeud F, Reymond A, Kapranov P, Rozowsky J, Zheng D, Castelo R, Frankish A, Harrow J, Ghosh S, Sandelin A, Hofacker IL, Baertsch R, Keefe D, Dike S, Cheng J, Hirsch HA, Sekinger EA, Lagarde J, Abril JF, Shahab A, Flamm C, Fried C, Hackermuller J, Hertel J, Lindemeyer M, Missal K, Tanzer A, Washietl S, Korbel J, Emanuelsson O, Pedersen JS, Holroyd N, Taylor R, Swarbreck D, Matthews N, Dickson MC, Thomas DJ, Weirauch MT, Gilbert J, Drenkow J, Bell I, Zhao X, Srinivasan KG, Sung WK, Ooi HS, Chiu KP, Foissac S, Alioto T, Brent M, Pachter L, Tress ML, Valencia A, Choo SW, Choo CY, Ucla C, Manzano C, Wyss C, Cheung E, Clark TG, Brown JB, Ganesh M, Patel S, Tammana H, Chrast J, Henrichsen CN, Kai C, Kawai J, Nagalakshmi U, Wu J, Lian Z, Lian J, Newburger P, Zhang X, Bickel P, Mattick JS, Carninci P, Hayashizaki Y, Weissman S, Hubbard T, Myers RM, Rogers J, Stadler PF, Lowe TM, Wei CL, Ruan Y, Struhl K, Gerstein M, Antonarakis SE, Fu Y, Green ED, Karaoz U, Siepel A, Taylor J, Liefer LA, Wetterstrand KA, Good PJ, Feingold EA, Guyer MS, Cooper GM, Asimenos G, Dewey CN, Hou M, Nikolaev S, Montoya-Burgos JI, Loytynoja A, Whelan S, Pardi F, Massingham T, Huang H, Zhang NR, Holmes I, Mullikin JC, Ureta-Vidal A, Paten B, Seringhaus M, Church D, Rosenbloom K, Kent WJ, Stone EA, N. C. S. Program, C. Baylor College of Medicine Human Genome Sequencing, C. Washington University Genome Sequencing, Broad I, I. Children’s Hospital Oakland Research, Batzoglou S, Goldman N, Hardison RC, Haussler D, Miller W, Sidow A, Trinklein ND, Zhang ZD, Barrera L, Stuart R, King DC, Ameur A, Enroth S, Bieda MC, Kim J, Bhinge AA, Jiang N, Liu J, Yao F, Vega VB, Lee CW, Ng P, Shahab A, Yang A, Moqtaderi Z, Zhu Z, Xu X, Squazzo S, Oberley MJ, Inman D, Singer MA, Richmond TA, Munn KJ, Rada-Iglesias A, Wallerman O, Komorowski J, Fowler JC, Couttet P, Bruce AW, Dovey OM, Ellis PD, Langford CF, Nix DA, Euskirchen G, Hartman S, Urban AE, Kraus P, Van Calcar S, Heintzman N, Kim TH, Wang K, Qu C, Hon G, Luna R, Glass CK, Rosenfeld MG, Aldred SF, Cooper SJ, Halees A, Lin JM, Shulha HP, Zhang X, Xu M, Haidar JN, Yu Y, Ruan Y, Iyer VR, Green RD, Wadelius C, Farnham PJ, Ren B, Harte RA, Hinrichs AS, Trumbower H, Clawson H, Hillman-Jackson J, Zweig AS, Smith K, Thakkapallayil A, Barber G, Kuhn RM, Karolchik D, Armengol L, Bird CP, de Bakker PI, Kern AD, Lopez-Bigas N, Martin JD, Stranger BE, Woodroffe A, Davydov E, Dimas A, Eyras E, Hallgrimsdottir IB, Huppert J, Zody MC, Abecasis GR, Estivill X, Bouffard GG, Guan X, Hansen NF, Idol JR, Maduro VV, Maskeri B, McDowell JC, Park M, Thomas PJ, Young AC, Blakesley RW, Muzny DM, Sodergren E, Wheeler DA, Worley KC, Jiang H, Weinstock GM, Gibbs RA, Graves T, Fulton R, Mardis ER, Wilson RK, Clamp M, Cuff J, Gnerre S, Jaffe DB, Chang JL, Lindblad-Toh K, Lander ES, Koriabine M, Nefedov M, Osoegawa K, Yoshinaga Y, Zhu B, de Jong PJ. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007;447(7146):799–816.

    Article  CAS  Google Scholar 

  • Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev. 2002;23(5):599–622.

    Article  CAS  PubMed  Google Scholar 

  • Fairbairn DW, Olive PL, O’Neill KL. The comet assay: a comprehensive review. Mutat Res. 1995;339(1):37–59.

    Article  CAS  PubMed  Google Scholar 

  • Fasshauer M, Paschke R. Regulation of adipocytokines and insulin resistance. Diabetologia. 2003;46(12):1594–603.

    Article  CAS  PubMed  Google Scholar 

  • Fedorova M, Bollineni RC, Hoffmann R. Protein carbonylation as a major hallmark of oxidative damage: update of analytical strategies. Mass Spectrom Rev. 2014;33:79–97.

    Article  CAS  PubMed  Google Scholar 

  • Fialkow L, Wang Y, Downey GP. Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol Med. 2007;42(2):153–64.

    Article  CAS  PubMed  Google Scholar 

  • Gambhir JK, Lali P, Jain AK. Correlation between blood antioxidant levels and lipid peroxidation in rheumatoid arthritis. Clin Biochem. 1997;30(4):351–5.

    Article  CAS  PubMed  Google Scholar 

  • Go YM, Jones DP. The redox proteome. J Biol Chem. 2013;288(37):26512–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gur M, Yildiz A, Demirbag R, Yilmaz R, Kocyigit A, Celik H, Aksoy N. Increased lymphocyte deoxyribonucleic acid damage in patients with cardiac syndrome X. Mutat Res. 2007;617(1–2):8–15.

    Article  CAS  PubMed  Google Scholar 

  • Haghdoost S, Maruyama Y, Pecoits-Filho R, Heimburger O, Seeberger A, Anderstam B, Suliman ME, Czene S, Lindholm B, Stenvinkel P, Harms-Ringdahl M. Elevated serum 8-oxo-dG in hemodialysis patients: a marker of systemic inflammation? Antioxid Redox Signal. 2006;8(11–12):2169–73.

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B, Lee CY. Using isoprostanes as biomarkers of oxidative stress: some rarely considered issues. Antioxid Redox Signal. 2010;33(2):145–56.

    Article  CAS  Google Scholar 

  • Henriksen T, Hillestrom PR, Poulsen HE, Weimann A. Automated method for the direct analysis of 8-oxo-guanosine and 8-oxo-2′-deoxyguanosine in human urine using ultraperformance liquid chromatography and tandem mass spectrometry. Free Radic Biol Med. 2009;47(5):629–35.

    Article  CAS  PubMed  Google Scholar 

  • Hofer T, Badouard C, Bajak E, Ravanat JL, Mattsson A, Cotgreave IA. Hydrogen peroxide causes greater oxidation in cellular RNA than in DNA. Biol Chem. 2005;386(4):333–7.

    Article  CAS  PubMed  Google Scholar 

  • Honda K, Smith MA, Zhu X, Baus D, Merrick WC, Tartakoff AM, Hattier T, Harris PL, Siedlak SL, Fujioka H, Liu Q, Moreira PI, Miller FP, Nunomura A, Shimohama S, Perry G. Ribosomal RNA in Alzheimer disease is oxidized by bound redox-active iron. J Biol Chem. 2005;280(22):20978–86.

    Article  CAS  PubMed  Google Scholar 

  • Honda A, Yamashita K, Hara T, Ikegami T, Miyazaki T, Shirai M, Xu G, Numazawa M, Matsuzaki Y. Highly sensitive quantification of key regulatory oxysterols in biological samples by LC-ESI-MS/MS. J Lipid Res. 2009;50(2):350–7.

    Article  CAS  PubMed  Google Scholar 

  • Huang LC, Clarkin KC, Wahl GM. Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest. Proc Natl Acad Sci U S A. 1996;93(10):4827–32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hussain SP, Schwank J, Staib F, Wang XW, Harris CC. TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. Oncogene. 2007;26(15):2166–76.

    Article  CAS  PubMed  Google Scholar 

  • Isobe C, Abe T, Terayama Y. Homocysteine may contribute to pathogenesis of RNA damage in brains with Alzheimer’s disease. Neurodegener Dis. 2009;6(5–6):252–7.

    Article  CAS  PubMed  Google Scholar 

  • Jacob KD, Noren Hooten N, Trzeciak AR, Evans MK. Markers of oxidant stress that are clinically relevant in aging and age-related disease. Mech Ageing Dev. 2013;134(3–4):139–57.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Janssen LJ. Isoprostanes and lung vascular pathology. Am J Respir Cell Mol Biol. 2008;39(4):383–9.

    Article  CAS  PubMed  Google Scholar 

  • Kanias T, Acker JP. Biopreservation of red blood cells–the struggle with hemoglobin oxidation. FEBS J. 2010;277(2):343–56.

    Article  CAS  PubMed  Google Scholar 

  • Kasapoglu M, Ozben T. Alterations of antioxidant enzymes and oxidative stress markers in aging. Exp Gerontol. 2001;36(2):209–20.

    Article  CAS  PubMed  Google Scholar 

  • Kastle M, Grune T. Protein oxidative modification in the aging organism and the role of the ubiquitin proteasomal system. Curr Pharm Des. 2011;17(36):4007–22.

    Article  PubMed  Google Scholar 

  • Kedziora-Kornatowska K, Szewczyk-Golec K, Czuczejko J, van Marke K, de Lumen H, Pawluk J, Motyl MK, Kedziora J. Effect of melatonin on the oxidative stress in erythrocytes of healthy young and elderly subjects. J Pineal Res. 2007;42(2):153–8.

    Article  CAS  PubMed  Google Scholar 

  • Kong Q, Shan X, Chang Y, Tashiro H, Lin CL. RNA oxidation: a contributing factor or an epiphenomenon in the process of neurodegeneration. Free Radic Res. 2008;42(9):773–7.

    Article  CAS  PubMed  Google Scholar 

  • Kosower NS, Kosower EM. The glutathione status of cells. Int Rev Cytol. 1978;54:109–60.

    Article  CAS  PubMed  Google Scholar 

  • Kuo LJ, Yang LX. Gamma-H2AX – a novel biomarker for DNA double-strand breaks. In Vivo. 2008;22(3):305–9.

    CAS  PubMed  Google Scholar 

  • Larsen ML, Horder M, Mogensen EF. Effect of long-term monitoring of glycosylated hemoglobin levels in insulin-dependent diabetes mellitus. N Engl J Med. 1990;323(15):1021–5.

    Article  CAS  PubMed  Google Scholar 

  • Lehman R, Krumholz HM. Tight control of blood glucose in long standing type 2 diabetes. BMJ. 2009;338:b800.

    Article  PubMed  Google Scholar 

  • Levine RL, Stadtman ER. Oxidative modification of proteins during aging. Exp Gerontol. 2001;36(9):1495–502.

    Article  CAS  PubMed  Google Scholar 

  • Libby P, Ridker PM. Inflammation and atherosclerosis: role of C-reactive protein in risk assessment. Am J Med. 2004;116(Suppl 6A):9S–16.

    Article  PubMed  Google Scholar 

  • Lindahl T. Instability and decay of the primary structure of DNA. Nature. 1993;362(6422):709–15.

    Article  CAS  PubMed  Google Scholar 

  • Little RR, Sacks DB. HbA1c: how do we measure it and what does it mean? Curr Opin Endocrinol Diabetes Obes. 2009;16(2):113–8.

    Article  PubMed  Google Scholar 

  • Lyons TJ, Basu A. Biomarkers in diabetes: hemoglobin A1c, vascular and tissue markers. Transl Res. 2012;159(4):303–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Maeda H, Akaike T. Nitric oxide and oxygen radicals in infection, inflammation, and cancer. Biochemistry (Mosc). 1998;63(7):854–65.

    CAS  Google Scholar 

  • Mano J. Reactive carbonyl species: their production from lipid peroxides, action in environmental stress, and the detoxification mechanism. Plant Physiol Biochem. 2012;59:90–7.

    Article  CAS  PubMed  Google Scholar 

  • Martinet W, de Meyer GR, Herman AG, Kockx MM. Reactive oxygen species induce RNA damage in human atherosclerosis. Eur J Clin Invest. 2004;34(5):323–7.

    Article  CAS  PubMed  Google Scholar 

  • Mastaloudis A, Yu TW, O’Donnell RP, Frei B, Dashwood RH, Traber MG. Endurance exercise results in DNA damage as detected by the comet assay. Free Radic Biol Med. 2004;36(8):966–75.

    Article  CAS  PubMed  Google Scholar 

  • Matsubara LS, Machado PE. Age-related changes of glutathione content, glutathione reductase and glutathione peroxidase activity of human erythrocytes. Braz J Med Biol Res. 1991;24(5):449–54.

    CAS  PubMed  Google Scholar 

  • Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts 2nd LJ. A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci U S A. 1990;87(23):9383–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Morrow JD, Awad JA, Kato T, Takahashi K, Badr KF, Roberts 2nd LJ, Burk RF. Formation of novel non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in carbon tetrachloride hepatotoxicity. An animal model of lipid peroxidation. J Clin Invest. 1992a;90(6):2502–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Morrow JD, Awad JA, Boss HJ, Blair IA, Roberts 2nd LJ. Non-cyclooxygenase-derived prostanoids (F2-isoprostanes) are formed in situ on phospholipids. Proc Natl Acad Sci U S A. 1992b;89(22):10721–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Moynahan ME, Jasin M. Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol. 2010;11(3):196–207.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nagababu E, Rifkind JM. Formation of fluorescent heme degradation products during the oxidation of hemoglobin by hydrogen peroxide. Biochem Biophys Res Commun. 1998;247(3):592–6.

    Article  CAS  PubMed  Google Scholar 

  • Nagababu E, Mohanty JG, Bhamidipaty S, Ostera GR, Rifkind JM. Role of the membrane in the formation of heme degradation products in red blood cells. Life Sci. 2010;86(3–4):133–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nakamura AJ, Chiang YJ, Hathcock KS, Horikawa I, Sedelnikova OA, Hodes RJ, Bonner WM. Both telomeric and non-telomeric DNA damage are determinants of mammalian cellular senescence. Epigenetics Chromatin. 2008;1(1):6.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Nakamura T, Cho DH, Lipton SA. Redox regulation of protein misfolding, mitochondrial dysfunction, synaptic damage, and cell death in neurodegenerative diseases. Exp Neurol. 2012;238(1):12–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Niki E. Lipid peroxidation: physiological levels and dual biological effects. Free Radic Biol Med. 2009;47(5):469–84.

    Article  CAS  PubMed  Google Scholar 

  • Niki E, Yoshida Y, Saito Y, Noguchi N. Lipid peroxidation: mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun. 2005;338(1):668–76.

    Article  CAS  PubMed  Google Scholar 

  • Noren Hooten N, Ejiogu N, Zonderman AB, Evans MK. Association of oxidative DNA damage and C-reactive protein in women at risk for cardiovascular disease. Arterioscler Thromb Vasc Biol. 2012;32(11):2776–84.

    Article  PubMed  CAS  Google Scholar 

  • Nouroog-Zadeh J. Key issues in F2-isoprostane analysis. Biochem Soc Trans. 2008;36(Pt 5):1060–5.

    Article  CAS  Google Scholar 

  • Nunomura A, Perry G, Hirai K, Aliev G, Takeda A, Chiba S, Smith MA. Neuronal RNA oxidation in Alzheimer’s disease and Down’s syndrome. Ann N Y Acad Sci. 1999;893:362–4.

    Article  CAS  PubMed  Google Scholar 

  • Pardo B, Gomez-Gonzalez B, Aguilera A. DNA repair in mammalian cells: DNA double-strand break repair: how to fix a broken relationship. Cell Mol Life Sci. 2009;66(6):1039–56.

    Article  CAS  PubMed  Google Scholar 

  • Poulsen HE, Nadal LL, Broedbaek K, Nielsen PE, Weimann A. Detection and interpretation of 8-oxodG and 8-oxoGua in urine, plasma and cerebrospinal fluid. Biochim Biophys Acta. 2014;1840(2):801–8.

    Article  CAS  PubMed  Google Scholar 

  • Reilly M, Delanty N, Lawson JA, FitzGerald GA. Modulation of oxidant stress in vivo in chronic cigarette smokers. Circulation. 1996;94(1):19–25.

    Article  CAS  PubMed  Google Scholar 

  • Rhee Y, Valentine MR, Termini J. Oxidative base damage in RNA detected by reverse transcriptase. Nucleic Acids Res. 1995;23(16):3275–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rifkind JM, Ramasamy S, Manoharan PT, Nagababu E, Mohanty JG. Redox reactions of hemoglobin. Antioxid Redox Signal. 2004;6(3):657–66.

    Article  CAS  PubMed  Google Scholar 

  • Roberts LJ, Morrow JD. Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo. Free Radic Biol Med. 2000;28(4):505–13.

    Article  CAS  PubMed  Google Scholar 

  • Rozalski R, Siomek A, Gackowski D, Foksinski M, Gran C, Klungland A, Olinski R. Substantial decrease of urinary 8-oxo-7,8-dihydroguanine, a product of the base excision repair pathway, in DNA glycosylase defective mice. Int J Biochem Cell Biol. 2005;37(6):1331–6.

    Article  CAS  PubMed  Google Scholar 

  • Ryan KA, Smith Jr MF, Sanders MK, Ernst PB. Reactive oxygen and nitrogen species differentially regulate Toll-like receptor 4-mediated activation of NF-kappa B and interleukin-8 expression. Infect Immun. 2004;72(4):2123–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Samiec PS, Drews-Botsch C, Flagg EW, Kurtz JC, Sternberg Jr P, Reed RL, Jones DP. Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes. Free Radic Biol Med. 1998;24(5):699–704.

    Article  CAS  PubMed  Google Scholar 

  • Schurman SH, Dunn CA, Greaves R, Yu B, Ferrucci L, Croteau DL, Seidman MM, Bohr VA. Age-related disease association of endogenous gamma-H2AX foci in mononuclear cells derived from leukapheresis. PLoS One. 2012;7(9):e45728.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shan X, Lin CL. Quantification of oxidized RNAs in Alzheimer’s disease. Neurobiol Aging. 2006;27(5):657–62.

    Article  CAS  PubMed  Google Scholar 

  • Shen Z, Wu W, Hazen SL. Activated leukocytes oxidatively damage DNA, RNA, and the nucleotide pool through halide-dependent formation of hydroxyl radical. Biochemistry. 2000;39(18):5474–82.

    Article  CAS  PubMed  Google Scholar 

  • Sinha K, Das J, Pal PB, Sil PC. Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol. 2013;87(7):1157–80.

    Article  CAS  PubMed  Google Scholar 

  • Siomek A, Rytarowska A, Szaflarska-Poplawska A, Gackowski D, Rozalski R, Dziaman T, Czerwionka-Szaflarska M, Olinski R. Helicobacter pylori infection is associated with oxidatively damaged DNA in human leukocytes and decreased level of urinary 8-oxo-7,8-dihydroguanine. Carcinogenesis. 2006;27(3):405–8.

    Article  CAS  PubMed  Google Scholar 

  • Sircar D, Subbaiah PV. Isoprostane measurement in plasma and urine by liquid chromatography-mass spectrometry with one-step sample preparation. Clin Chem. 2007;53(2):251–8.

    Article  CAS  PubMed  Google Scholar 

  • Skold A, Cosco DL, Klein R. Methemoglobinemia: pathogenesis, diagnosis, and management. South Med J. 2011;104(11):757–61.

    Article  PubMed  Google Scholar 

  • Sorci G, Riuzzi F, Giambanco I, Donato R. RAGE in tissue homeostasis, repair and regeneration. Biochim Biophys Acta. 2013;1833(1):101–9.

    Article  CAS  PubMed  Google Scholar 

  • Szanton SL, Rifkind JM, Mohanty JG, Miller 3rd ER, Thorpe RJ, Nagababu E, Epel ES, Zonderman AB, Evans MK. Racial discrimination is associated with a measure of red blood cell oxidative stress: a potential pathway for racial health disparities. Int J Behav Med. 2012;19(4):489–95.

    Article  PubMed Central  PubMed  Google Scholar 

  • Tanaka M, Chock PB, Stadtman ER. Oxidized messenger RNA induces translation errors. Proc Natl Acad Sci U S A. 2007;104(1):66–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tetik S, Ahmad S, Alturfan AA, Fresko I, Disbudak M, Sahin Y, Aksoy H, Yardimci KT. Determination of oxidant stress in plasma of rheumatoid arthritis and primary osteoarthritis patients. Indian J Biochem Biophys. 2010;47(6):353–8.

    CAS  PubMed  Google Scholar 

  • Thompson D, Pepys MB, Wood SP. The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure. 1999;7(2):169–77.

    Article  CAS  PubMed  Google Scholar 

  • Toda T, Nakamura M, Morisawa H, Hirota M, Nishigaki R, Yoshimi Y. Proteomic approaches to oxidative protein modifications implicated in the mechanism of aging. Geriatr Gerontol Int. 2010;10 Suppl 1:S25–31.

    Article  PubMed  Google Scholar 

  • Trzeciak M, Glen J, Roszkiewicz J, Nedoszytko B. Association of single nucleotide polymorphism of interleukin-18 with atopic dermatitis. J Eur Acad Dermatol Venereol. 2010;24(1):78–9.

    Article  CAS  PubMed  Google Scholar 

  • Trzeciak AR, Mohanty JG, Jacob KD, Barnes J, Ejiogu N, Lohani A, Zonderman AB, Rifkind JM, Evans MK. Oxidative damage to DNA and single strand break repair capacity: relationship to other measures of oxidative stress in a population cohort. Mutat Res. 2012;736(1–2):93–103.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • van Leeuwen FW, de Kleijn DP, van den Hurk HH, Neubauer A, Sonnemans MA, Sluijs JA, Koycu S, Ramdjielal RD, Salehi A, Martens GJ, Grosveld FG, Peter J, Burbach H, Hol EM. Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer’s and down patients. Science. 1998;279(5348):242–7.

    Article  PubMed  Google Scholar 

  • Vangaveti V, Baune BT, Kennedy RL. Hydroxyoctadecadienoic acids: novel regulators of macrophage differentiation and atherogenesis. Ther Adv Endocrinol Metab. 2010;1(2):51–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vaya J, Szuchman A, Tavori H, Aluf Y. Oxysterols formation as a reflection of biochemical pathways: summary of in vitro and in vivo studies. Chem Phys Lipids. 2011;164(6):438–42.

    Article  CAS  PubMed  Google Scholar 

  • Weimann A, Belling D, Poulsen HE. Quantification of 8-oxo-guanine and guanine as the nucleobase, nucleoside and deoxynucleoside forms in human urine by high-performance liquid chromatography-electrospray tandem mass spectrometry. Nucleic Acids Res. 2002;30(2):E7.

    Article  PubMed Central  PubMed  Google Scholar 

  • Wu IC, Shiesh SC, Kuo PH, Lin XZ. High oxidative stress is correlated with frailty in elderly Chinese. J Am Geriatr Soc. 2009;57(9):1666–71.

    Article  PubMed  Google Scholar 

  • Xu L, Korade Z, Rosado Jr DA, Liu W, Lamberson CR, Porter NA. An oxysterol biomarker for 7-dehydrocholesterol oxidation in cell/mouse models for Smith-Lemli-Opitz syndrome. J Lipid Res. 2011;52(6):1222–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yamagishi S, Matsui T. Soluble form of a receptor for advanced glycation end products (sRAGE) as a biomarker. Front Biosci (Elite Ed). 2010;2:1184–95.

    Article  Google Scholar 

  • Yoshida Y, Niki E. Bio-markers of lipid peroxidation in vivo: hydroxyoctadecadienoic acid and hydroxycholesterol. Biofactors. 2006;27(1–4):195–202.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fawaz Alzaid .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Alzaid, F., Patel, V.B., Preedy, V.R. (2014). Biomarkers of Oxidative Stress in Blood. In: Preedy, V., Patel, V. (eds) General Methods in Biomarker Research and their Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7740-8_41-1

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-7740-8_41-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-7740-8

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics