Zusammenfassung
Sauerstoff ist für eukaryontische Zellen essenziell für die Energieproduktion. Ein Leben in einer aeroben Umgebung bedeutet aber auch eine ständige Konfrontation mit reaktiven Sauerstoffverbindungen, die z. B. als Nebenprodukte des aeroben Stoffwechsels entstehen. Sauerstoffradikale werden ebenfalls im Rahmen von Immunaktivierungsvorgängen durch immunkompetente Zellen massiv freigesetzt und können Schäden an Zellstrukturen verursachen. Die hauptsächlichen Ziele der Radikale sind hierbei Enzyme, Zellmembrane sowie die DNS. Oxidativer Stress entsteht, wenn eine zu große Bildung von Sauerstoffradikalen einem zu geringen Pool an Antioxidantien gegenübersteht. Die Entdeckung, dass oxidativer Stress eine wichtige Rolle in der Pathogenese einer großen Reihe von Erkrankungen spielt, hat die Erforschung dieser Vorgänge in den Fokus des Interesses gesetzt. Unterschiedliche Methoden wurden entwickelt, um oxidativen Stress in vivo zu quantifizieren, wie die Messungen von Oxidationsprodukten bei der Lipidperoxidation, oxydierte Proteine oder DNS. Alternativ dazu ist die Evaluierung des Verbrauchs von Antioxidantien. Diese Zusammenfassung gibt einen Überblick über verschiedener Methoden zur Quantifizierung von oxidativem Stress in vivo.
Abstract
Oxygen is required by eukaryotic cells for energy production. Living in an aerobic environment brings with the exposure of cells to reactive oxygen species (ROS). ROS for example accumulate as byproducts of the aerobic metabolism, and a substantial endogenous generation of ROS occurs during immune response by immunocompetent cells. Massive occurrence of ROS results in oxidative damage of cellular components. The primary targets of ROS are enzymes, cell membranes, and DNA. Oxidative stress is defined by an overwhelming occurrence of ROS opposed by an exhausted pool of antioxidants. In the last decade, the role of oxidative stress in the pathogenesis of a wide range of human diseases became obvious, and determination of the phenomenon of oxidative stress moved into the focus of interest. Several approaches were developed to quantify this condition. Among them are measurements of oxidation products such as lipid peroxidation, oxidized protein, or DNA. Alternatively, oxidative stress can be determined by the loss of antioxidants. This review briefly summarizes current available methods for the quantification of oxidative stress in vivo.
Schlüsselwörter
Sauerstoffradikale - Antioxidantien - Immunantwort - Neopterin
Key words
Reactive oxygen species - antioxidants - immune response - neopterin
References
1
Hurst J K, Barette W C.
Leukocyte oxygen activation and microbicidal oxidative toxins.
Crit Rev Biochem Mol Biol.
1989;
24
271-328
2
Kohen R, Nydka A.
Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification.
Toxicol Pathol.
2002;
30
620-650
3
Halliwell B.
Free radicals, antioxidants, and human disease: curiosity, cause, or consequence?.
Lancet.
1984;
344
721-724
4
Powis G, Briehl M, Oblong J.
Redox signalling and the control of cell growth and death.
Pharmac Ther.
1995;
65
149-173
5
Davies K J.
Protein damage and degradation of oxygen radicals. I. General aspects.
J Biol Chem.
1987;
262
9895-9901
6 Halliwell B, Gutteridge J MC. Free radicals in biology and medicine. 2nd ed. Oxford; Clarendon Press 1990
7
Beckman K B, Ames B N.
Oxidative decay of DNA.
J Biol Chem.
1997;
272
19633-19636
8
Esterbauer H, Schaur R J, Zollner H.
Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes.
Free Radic Biol Med.
1991;
11
81-128
9
Bird R P, Draper H H.
Comparative studies on different methods of malondialdehyde determination.
Methods Enzymol.
1984;
105
299-305
10
Marnett L F, Tuttle M A.
Comparison of the mutagenicities of malondialdehyde and the side products formed during its chemical synthesis.
Cancer Res.
1980;
40
276-282
11
Benzie I F.
Lipid peroxidation: a review of causes, consequences, measurement and dietary influences.
Int J Fodd Sci Nutr.
1996;
47
233-261
12
Dib M, Garrel C, Favie A, Robin V, Desnuelle C.
Can malondialdehyde be used as a biological marker of progression in neurodegenerative disease?.
J Neurol.
2002;
249
367-374
13
Valles J, Aznar J, Santos M T, Fernandez M A.
Elevated lipid peroxide levels in platelets of chronic ischemic heart disease patients.
Thromb Res.
1882;
27
585-589
14
Roberts L J, Morrow J D.
Measurement of F2-isoprostanes as an index of oxidative stress in vivo.
Free Radic Biol Med.
2000;
28
505-513
15
Praticò D.
F2-isoprostanes, sensitive and specific non-invasive indices of lipid peroxidation in vivo.
Atherosclerosis.
1999;
147
1-10
16
Patrono C, FitzGerald G A.
Isoprostanes: potential markers of oxidant stress in atherothrombotic disease.
Arterioscler Thromb Vasc Biol.
1997;
17
2309-2315
17
Jiang Z Y, Hunt J V, Wolff S P.
Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in lowdensity lipoprotein.
Anal Biochem.
1992;
202
384-389
18
Davies M F, Fu S, Wang H, Dean R T.
Stable markers of oxidant damage to proteins and their application in the study of human disease.
Free Radic Biol Med.
1999;
27
1151-1163
19
Beckman J S, Koppenol W H.
Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly.
Am J Physiol.
1996;
271
C1424-1437
20
Halliwell B.
Reactive oxygen species and the central nervous system.
J Neurochem.
1992;
59
1609-1623
21
Good P F, Hsu A, Werner P, Perl D P, Oanow C W.
Protein nitration in Parkinson's disease.
J Neuropathol Exp Neurol.
1998;
57
338-342
22
Shigenaga M K, Gimeno C J, Ames B N.
Urinary 8-hydroxy-2'-deoxyguanosine as a biomarker of in vivo oxidative DNA damage.
Proc Natl Acad Sci USA.
1989;
86
9697-9701
23
Iiada T, Furuta A, Kawashima M, Nishida J, Nakabeppu Y, Iwaki T.
Accumulation of 8-oxo-2'-deoxyguanosine and increased expression of hMTH1 protein in brain tumors.
Neurooncol.
2001;
3
73-81
24
Tietze F.
Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues.
Anal Biochem.
1969;
27
502-522
25
Brigelius R, Muckel C, Akerboom T P, Sies H.
Identification and quantitation of glutathione in hepatic protein mixed disulfides and its relationship to glutathione disulfide.
Biochem Pharmacol.
1983;
32
2529-2534
26
Reed D J, Babson J R, Beatty P W, Brodie A E, Ellis W W, Potter D W.
High-performance liquid chromatography analysis of nanomole levels of glutathione, glutathione disulfide, and related thiols and disulfides.
Anal Biochem.
1980;
106
55-62
27
Newton G L, Dorian R, Fahey R C.
Analysis of biological thiols: derivatization with monobromobimane and separation by reverse phase high-performance liquid chromatography.
Anal Biochem.
1981;
114
383-387
28
Samiec P S, Drews-Botsch F, Flagg E W, Kurtz J C, Sterinberg P, Reed R L, Jones D P.
Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes.
Free Radic Biol Med.
1998;
24
699-704
29
Navarro J, Obrador E, Carretero J, Petschen I, Avino J, Perez P, Estrela J M.
Changes in glutathione status and the antioxidant system in blood and in cancer cells associated with tumour growth in vivo.
Free Radic Biol Med.
1999;
26
410-418
30
Herzenberg L A, Rosa S C De, Dubs J G, Roederer M, Anderson M T, Ela S W, Dereninski S C, Herzenberg L A.
Glutathione deficiency is associated with impaired survival in HIV disease.
Proc Natl Acad Sci USA.
1997;
94
1967-1972
31
Ross R, Milzani A, Dalle-Donne I, Giustarini D, Lusini L, Colombo R, Simplicio P Di.
Blood glutathione disulfide: In vivo factor or in vitro artefact?.
Clin Chem.
2002;
48
742-753
32
Brigelium-Flohé R, Kelly F J, Salonen J R, Neuzil J, Zingg J M, Azzi A.
The European perspective on vitamin E: current knowledge and future research.
Am J Clin Nutr.
2002;
76
703-716
33
Benzie I F, Strain J J.
The ferric reducing ability of plasma (FRAP) as a measure of „antioxidant power”: the FRAP assay.
Anal Biochem.
1996;
239
70-76
34
Güler K, Palanduz S, Ademoglu E, Sahnayenli N, Gökkusu C, Vatanserver S.
Total antioxidant status, lipid parameters, lipid peroxidation and glutathione levels in patients with acute myocardial infarction.
Med Sci Res.
1998;
26
105-106
35
Miller N J, Rice-Evans C, Davies M J, Gopinathan V, Milner A.
A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in plasma and body fluids.
Meth Enzymol.
1994;
234
279-293
36
Rice-Evans C, Miller N J.
Total antioxidant status in plasma and body fluids.
Meth Enzymol.
1994;
234
279-293
37
Wayner D D, Burton G W, Ingold K U, Locke S.
Quantitative measurement of the total, peroxyl radical-trapping antioxidant capacity of human blood plasma by controlled peroxidation.
FEBS Lett.
1985;
187
33-37
38
Alho H, Leinonen J.
Total antioxidant activity measured by chemiluminescence methods.
Meth Enzymol.
1999;
299
3-14
39
Glazer A N.
Phycoerythrin fluorescence-based assay for reactive oxygen species.
Meth Enzymol.
1990;
186
161-168
40
Cao G, Booth S L, Sadowski J A, Prior R L.
Increases in human plasma antioxidant capacity following consumption of controlled diets high in fruits and vegetables.
Am J Clin Nutr.
1998;
68
1081-1087
41
Cao G, Prior R L.
Comparison of different analytical methods for assessing total antioxidant capacity of human serum.
Clin Chem.
1998;
44
1309-1315
42
Jackson P, Loughrey C M, Leghtbody J H, McNamee P T, Young I S.
Effect of hemodialysis on total antioxidant capacity and serum antioxidants in patients with chronic renal failure.
Clin Chem.
1995;
41
1135-1138
43
Gerardi G M, Usberti M, Martini G, Alberini A, Sugherini L, Pompella A, Lorenzo D Di.
Plasma total antioxidant capacity in hemodialyzed patients and its relationships to other biomarkers of oxidative stress and lipid peroxidation.
Clin Chem Lab Med.
2002;
40
104-110
44
Cao G, Shukitt-Hale B, Bichford P C, Joseph J A, McEwen J, Prior R L.
Hyperoxida-induced changes in antioxidant capacity and the effect of dietary antioxidants.
J Appl Physiol.
1999;
86
1817-1822
45
Farinati F, Cardin R, Degan P, Maria N De, Floyd R A, Thiel D H Van, Naccarato R.
Oxidative DNA damage in circulating leukocytes occurs as an early event in chronic HCV infection.
Free Radic Biol Med.
1999;
27
1284-1291
46
O'Byrne K F, Dalgleish A G.
Chronic immune activation and inflammation as the cause of malignancy.
Brit J Cancer.
2001;
85
473-483
47
Nathan C F.
Peroxide and pteridine: a hypothesis on the regulation of macrophage antimicrobial activity by interferon gamma.
Interferon.
1986;
7
125-143
48
Huber C, Batchelor J R, Fuchs D, Hausen A, Lang A, Niederwieser D, Reibnegger G, Swetly P, Troppmair J, Wachter H.
Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma.
J Exp Med.
1984;
160
310-316
49
Reibnegger G, Auhuber I, Fuchs D, Hausen A, Judmaier G, Prior C, Werner E R, Wachter H.
Urinary neopterin levels in acute viral hepatitis.
Hepatology.
1988;
8
771-774
50
Fuchs D, Hausen A, Reibnegger G, Werner E R, Dierich M P, Wachter H.
Neopterin as a marker for activated cell-mediated immunity: application in HIV infection.
Immunol Today.
1988;
9
150-155
51
Lim K L, Jones A C, Brown N S, Powell R J.
Urine neopterin as a parameter of disease activity in patients with systemic lupus erythematosus: comparisons with serum sIL-2R and antibodies to dsDNA, erythrocyte sedimentation rate, and plasma C3, C4, and C3 degradation products.
Ann Rheum Dis.
1993;
52
429-435
52
Hausen A, Fuchs D, Grunewald K, Huber H, Koenig K, Wachter H.
Urinary neopterine as marker for haematological neoplasias.
Clin Chim Acta.
1981;
117
297-305
53
Murr C, Bergant A, Widschwendter M, Heim K, Schröcksnadel H, Fuchs D.
Neopterin is an independent prognostic variable in females with breast cancer.
Clin Chem.
1999;
45
1998-2004
54
Margreiter R, Fuchs D, Hausen A, Huber C, Reibnegger G, Spielberger M, Wachter H.
Neopterin as a new biochemical marker for diagnosis of allograft rejection. Experience based upon evaluation of 100 consecutive cases.
Transplantation.
1983;
36
650-653
55
Tatzber F, Rabl H, Koriska K, Erhart U, Puhl H, Waeg G, Krebs A, Esterauer H.
Elevated serum neopterin levels in atherosclerosis.
Atherosclerosis.
1991;
89
203-208
56
Leblhuber F, Walli J, Demel U, Tilz G P, Widner B, Fuchs D.
Increased serum neopterin concentrations in patients with Alzheimer's disease.
Clin Chem Lab Med.
1999;
37
429-431
57
Widner B, Leblhuber F, Fuchs D.
Increased neopterin production and tryptophan degradation in advanced Parkinson's disease.
J Neural Transm.
2002;
109
181-189
58
Murr C, Fuchs D, Gossler W, Hausen A, Reibnegger G, Werner E R, Werner-Felmayer G, Esterbauer H, Wachter H.
Enhancement of hydrogen peroxide-induced luminol-dependent chemiluminescence by neopterin depends on the presence of iron chelator complexes.
FEBS Lett.
1994;
338
223-226
59
Herpfer I, Greilberger J, Ledinski G, Widner B, Fuchs D, Jurgens G.
Neopterin and 7,8-dihydroneopterin interfere with low density lipoprotein oxidation mediated by peroxynitrite and/or copper.
Free Radic Res.
2002;
36
509-520
60
Widner B, Baier-Bitterlich G, Wede I, Wirleitner B, Fuchs D.
Neopterin derivatives modulate the nitration of tyrosine by peroxynitrite.
Biochem Biophys Res Commun.
1998;
248
341-346
61
Kojima S, Icho T, Mori H, Arai T.
Enhancing potency of neopterin toward B-16 melanoma cell damage induced by UV-A irradiation and its possible application for skin tumor treatment.
Anticancer Res.
1995;
15
1975-1980
62
Weiss G, Fuchs D, Hausen A, Reibnegger G, Werner E R, Werner-Felmayer G, Semenitz E, Dierich M P, Wachter H.
Neopterin modulates toxicity mediated by reactive oxygen and chloride species.
FEBS Lett.
1993;
321
89-92
63
Reibnegger G, Fuchs D, Murr C, Dierich M P, Pfleiderer W, Wachter H.
Effects of pteridines on luminol-dependent chemiluminescence induced by chloramine-T.
Free Radic Biol Med.
1995;
18
515-523
64
Gieseg S P, Reibnegger G, Wachter H, Esterbauer H.
7,8 -dihydroneopterin inhibits low density lipoprotein oxidation in vitro. Evidence that this macrophage secreted pteridine is an anti-oxidant.
Free Radic Res.
1995;
23
123-136
65
Baier-Bitterlich G, Fuchs D, Murr C, Reibnegger G, Werner-Felmayer G, Sgonc R, Bock G, Dierich M P, Wachter H.
Effect of neopterin and 7,8-dihydroneopterin on tumor necrosis factor-alpha induced programmed cell death.
FEBS Lett.
1995;
364
234-238
66
Oettl K, Dikalov S, Freisleben H J, Mlekusch W, Reibnegger G.
Spin trapping study of antioxidant properties of neopterin and 7,8-dihydroneopterin.
Biochem Biophys Res Commun.
1997;
234
774-778
67
Thomas A H, Lorente C, Capparelli A L, Martinez C G, Braun A M, Oliveros E.
Singlet oxygen (1deltag) production by pterin derivatives in aqueous solutions.
Photochem Photobiol Sci.
2003;
2
245-250
68 Razumovitchi J A, Semenkova G N, Fuchs D, Cherenkevich S N. Influence of neopterin on the generation of reactive oxygen species in human neutrophils under the action of neopterin. FEBS Lett 2003, in press
69
Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, Nguyen-Khoa T, Nguyen A T, Zingraff J, Jungers P, Descamps-Latscha B.
Advanced oxidation protein products as a novel marker of oxidative stress in uremia.
Kidney Int.
1996;
49
1304-1313
70
Witko-Sarsat V, Friedlander M, Nguyen K hoa, Capeillere-Blandin C, Nguyen A T, Canteloup S, Dayer J M, Jungers P, Drueke T, Descamps-Latscha B.
Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure.
J Immunol.
1998;
161
2524-2532
71
Sattler W, Leblhuber F, Walli J, Widner B, Fuchs D.
Cerebrospinal fluid levels of α-tocopherol and neopterin in patients with dementia.
Pteridines.
1999;
10
220-224
72
Solichova D, Melichar B, Blaha V, Klejna M, Vavrova J, Palicka V, Zadak Z.
Biochemical profile and survival in nonagenarians.
Clin Biochem.
2001;
34
563-569
73
Hronek M, Zadak Z, Solichova D, Jandik P, Melichar B.
The association between specific nutritional antioxidants and manifestation of colorectal cancer.
Nutrition.
2000;
16
189-191
74
Zvetkova E, Wirleitner B, Tram N T, Schennach H, Fuchs D.
Aqueous extracts of Crinum latifolium (L.) and Camellia sinensis show immunomodulatory properties in human peripheral blood mononuclear cells.
Int Immunopharmacol.
2001;
1
2143-2150
75
Neurauter G, Wirleitner B, Schroecksnadel K, Schennach H, Fuchs D.
Red and white wine as well as grape juice modulate interferon-γ-induced neopterin production and tryptophan degradation in human PBMC.
Pteridines.
2003;
14
52
76
Heyden S.
Das Ende der Supplementierung mit antioxidantiven Vitaminen.
Aktuel Ernaehr Med.
2003;
28
113-120
77
El-Khairy L, Vollset S E, Refsum H, Ueland P M.
Plasma total cysteine, mortality, and cardiovascular disease hospitalizations: The Hordaland homocysteine study.
Clin Chem.
2003;
49
895-900
78
Wede I, Altindag Z Z, Widner B, Wachter H, Fuchs D.
Inhibition of xanthine oxidase by pterins.
Free Radic Res.
1998;
29
331-338
79
Baier-Bitterlich G, Fuchs D, Zangerle R, Baeuerle P A, Werner E R, Fresser F, Überall F, Baier G, Wachter H.
Trans-Activation of the HIV type 1 promoter by 7,8-dihydroneopterin in vitro.
AIDS Res Hum Retroviruses.
1997;
13
173-178
80
Überall F, Werner-Felmayer G, Schubert C, Grunicke H H, Wachter H, Fuchs D.
Neopterin derivatives together with cyclic guanosine monophosphate induce c-fos gene expression.
FEBS Lett.
1994;
352
11-14
81
Baier-Bitterlich G, Fuchs D, Wachter H.
7,8-dihydroneopterin upregulates interferon-gamma promoter in T cells.
Immunobiology.
1996;
196
350-355
82
Hoffmann G, Frede S, Kenn S, Smolny M, Wachter H, Fuchs D, Grote J, Rieder J, Schobersberger W.
Neopterin-induced tumor necrosis factor-alpha synthesis in vascular smooth muscle cells in vitro.
Int Arch Allergy Immunol.
1998;
116
240-245
83
Hoffmann G, Rieder J, Smolny M, Seibel M, Wirleitner B, Fuchs D, Schobersberger W.
Neopterin-induced expression of intercellular adhesion molecule-1 (ICAM-1) in type II-like alveolar epithelial cells.
Clin Exp Immunol.
1999;
118
435-440
84
Schobersberger W, Hoffmann G, Grote J, Wachter H, Fuchs D.
Induction of inducible nitric oxide synthase expression by neopterin in vascular smooth muscle cells.
FEBS Lett.
1995;
377
461-464
85
Baier-Bitterlich G, Baier G, Fuchs D, Bock G, Hausen A, Utermann G, Pavelka M, Wachter H.
Role of 7,8-dihydroneopterin in T-cell apoptosis and HTLV-1 transcription in vitro.
Oncogene.
1996;
13
2281-2285
Dr. Dietmar Fuchs
Institut für medizinische Chemie und Biochemie · Leopold-Franzens-Universität Innsbruck · Boltzmann-Institut für AIDS-Forschung
Fritz-Pregl-Straße 3
6020 Innsbruck · Austria
Phone: ++ 43/512/507-3519
Fax: ++ 43/512/507-2865
Email: dietmar.fuchs@uibk.ac.at