METHODS OF ESTIMATION AND THE ROLE OF RESPIRATORY BURST IN THE PATHOGENESIS OF INFECTIOUS AND INFLAMMATORY DISEASES

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  • Authors: Savchenko A.A.1,2, Kudryavtsev I.V.3,4, Borisov A.G.1,2
  • Affiliations:
    1. Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Scientific Research Institute of Medical Problems of the North, Krasnoyarsk
    2. Krasnoyarsk State Medical University named after prof. V.F. Voino-Yasenetsky, Krasnoyarsk
    3. Institute of Experimental Medicine, St. Petersburg
    4. Pavlov First Saint Petersburg State Medical University, St. Petersburg
  • Issue: Vol 7, No 4 (2017)
  • Pages: 327-340
  • Section: REVIEWS
  • Submitted: 20.01.2018
  • Accepted: 20.01.2018
  • Published: 20.01.2018
  • URL: https://iimmun.ru/iimm/article/view/590
  • DOI: https://doi.org/10.15789/2220-7619-2017-4-327-340
  • ID: 590


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Abstract

According to the modern concepts the respiratory burst directly related to the processes of phagocytosis characterizes the functional activity of phagocytic cells. This review presents modern methods for assessing the respiratory burst state of phagocytes based on cytofluorometric and chemiluminescent analysis. The sequence and mechanisms of the reactions of reactive oxygen species (ROS) synthesis in the process of respiratory cell burst are presented in detail. The sequence of synthesis from ROS with low bactericidal activity to ROS with high bactericidal activity is characterized. The review describes in detail the most popular dyes for cytofluorometric analysis to assess the levels of ROS synthesis. Characteristics and examples of the use of such dyes as dihydroethidine, dichlorodihydrofluorescein and dihydrorhodamine 123 are given. The main stages and mechanisms of the chemiluminescence reaction are presented. The features of the use of the main indicators (luminol and lucigenin) of the chemiluminescence reaction are described. A mechanism for estimating the parameters of the chemiluminescence reaction characterizing the features of the state and kinetics of the respiratory burst of phagocytic cells is given. The separate section of the review is devoted to the role of a respiratory burst in phagocytic cells in various immunopathological states. Data on the pathogenetic significance of changes in the intensity and kinetics of respiratory burst of phagocytes in infectious, inflammatory and oncological diseases were presented. Examples of new methods for diagnosing and predicting the course of the immunopathological states characters are presented on the basis of an assessment of the respiratory burst of phagocytic cells. The literature data show that at present, in the diagnosis and evaluation of the nature of the diseases characters the state of a respiratory burst is evaluated in various types of cells of innate immunity: neutrophils, monocytes, etc. It is concluded that the evaluation of the respiratory burst of phagocytic cells can be characterized as the fundamental mechanisms of reacting cells of innate immunity to pathogenic and regulatory effects, so to develop new highly sensitive methods for diagnosing and predicting the development and outcome of various immunopathological conditions. The presented methods of flow cytometry and chemiluminescence analysis make it possible to determine both the integral state of the respiratory explosion, and the levels and kinetic parameters of the synthesis of individual ROS.

About the authors

A. A. Savchenko

Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Scientific Research Institute of Medical Problems of the North, Krasnoyarsk;
Krasnoyarsk State Medical University named after prof. V.F. Voino-Yasenetsky, Krasnoyarsk

Email: igorek1981@yandex.ru
PhD, MD (Medicine), Professor, Head of the Laboratory of Molecular-Cell Physiology and Pathology, Scientific Research Institute of Medical Problems of the North Россия

I. V. Kudryavtsev

Institute of Experimental Medicine, St. Petersburg;
Pavlov First Saint Petersburg State Medical University, St. Petersburg

Author for correspondence.
Email: igorek1981@yandex.ru
PhD (Biology), Senior Researcher, Laboratory of Immunology, Institute of Experimental Medicine, St. Petersburg, Russian Federation; Senior Researcher, Department of Fundamental Medicine, Far Eastern Federal University, Vladivostok, Russian Federation; Associate Professor, Department of Immunology, Pavlov First St. Petersburg State Medical University Россия

A. G. Borisov

Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Scientific Research Institute of Medical Problems of the North, Krasnoyarsk;
Krasnoyarsk State Medical University named after prof. V.F. Voino-Yasenetsky, Krasnoyarsk

Email: igorek1981@yandex.ru
PhD (Medicine), Leading Researcher, Laboratory of Molecular-Cell Physiology and Pathology, Scientific Research Institute of Medical Problems of the North Россия

References

  1. Бердюгина О.В., Ершова А.В. Функционально-метаболические особенности фагоцитов крови при разных формах туберкулезного воспалительного процесса легких // Медицинская иммунология. 2016. Т. 18, № 1. С. 21–32. [Berdyugina O.V., Ershova A.V. Functional-metabolic features of blood phagocytes in different forms of tuberculous inflammatory process of the lungs. Meditsinskaya immunologiya = Medical Immunology, 2016, vol. 18, no. 1, pp. 21–32. doi: 10.15789/1563-0625-2016-1-21-32 (In Russ.)]
  2. Владимиров Ю.А., Проскурнина Е.В. Свободные радикалы и клеточная хемилюминесценция // Успехи биологической химии. 2009. Т. 49. С. 341–388. [Vladimirov Yu.A., Proskurnina E.V. Free radicals and cellular chemiluminescence. Uspekhi bio-logicheskoi khimii = Advances in Biochemistry, 2009, vol. 49, pp. 341–388. (In Russ.)]
  3. Куртасова Л.М., Зуков Р.А., Семенов Э.В. Особенности хемилюминесценции нейтрофилов периферической крови у онкоурологических больных в динамике заболевания // Медицинская иммунология. 2016. Т. 18, № 6. С. 589–594. [Kurtasova L.M., Zukov R.A., Semenov E.V. Features of chemiluminescence of peripheral blood neutrophils in oncourologic patients in the course of the disease dynamics. Meditsinskaya immunologiya = Medical Immunology (Russia), 2016, vol. 18, no. 6, pp. 589–594. doi: 10.15789/1563-0625-2016-6-589-594 (In Russ.)]
  4. Куртасова Л.М., Шакина Н.А., Шмидт А.Р. Клеточная чувствительность к интерферону-2 in vitro у детей с инфекционным мононуклеозом, вызванным вирусом Эпштейна–Барр // Медицинская иммунология. 2016. Т. 18, № 1. С. 79–84. [Kurtasova L.M., Shakina N.A., Schmidt A.R. In vitro cellular response to interferon-2 in children with infectious mononucleosis caused by Epstein-Barr virus. Meditsinskaya immunologiya = Medical Immunology (Russia), 2016, vol. 18, no. 1, pp. 79–84. doi: 10.15789/1563-0625-2016-1-79-84 (In Russ.)]
  5. Патент 2293988 Российская Федерация. Способ оценки чувствительности к интерферону у больных раком почки / Куртасова Л.М., Шкапова Е.А., Савченко А.А., Крыжановский А.И., Зуков Р.А., Рачкова Н.В. Заявители и патенто-обладатели: ГУ НИИ медицинских проблем Севера СО РАМН, Красноярский краевой онкологический диспансер; заявл. 10.09.2005; опубл. 20.02.2007 [Patent 2293988 Russian Federation. Method for assessing sensitivity to interferon in patients with kidney cancer / Kurtasova L.M., Shkapova E.A., Savchenko A.A., Kryzhanovskii A.I., Zukov R.A., Rachkova N.V. Applicants and patent holders: State Research Institute of Medical Problems of the North, Siberian Branch of the Russian Academy of Medical Sciences, Krasnoyarsk Regional Oncology Center; stat. 10.09.2005; publ. 20.02.2007]
  6. Савченко А.А., Борисов А.Г., Здзитовецкий Д.Э., Гвоздев И.И. Особенности цитокиновой регуляции респираторного взрыва нейтрофилов крови в прогнозе развития абдоминального сепсиса у больных распространенным гнойным перитонитом // Медицинская иммунология. 2016. Т. 18, № 5. С. 475–482. [Savchenko A.A., Borisov A.G., Zdzitovetsky D.E., Gvozdev I.I. Cytokine regulation of respiratory burst in blood neutrophils for prediction of abdominal sepsis in patients with extended purulent peritonitis. Meditsinskaya immunologiya = Medical Immunology (Russia), 2016, vol. 18, no. 5, pp. 475–482. doi: 10.15789/1563-0625-2016-5-475-482 (In Russ.)]
  7. Патент 2620560 Российская Федерация. Способ прогнозирования развития абдоминального сепсиса у больных с распространенным гнойным перитонитом / Савченко А.А., Борисов А.Г., Здзитовецкий Д.Э., Гвоздев И.И. Заявители и патентообладатели: ФИЦ КНЦ СО РАН; заявл. 10.11.2015; опубл. 26.05.2017 [Patent 2620560 Russian Federation. A method for predicting the development of abdominal sepsis in patients with advanced purulent peritonitis / Savchenko A.A., Borisov A.G., Zdzitovetskiy D.E., Gvozdev I.I. Applicants and patent holders: FIC KNTS SO RAN; stat. 10.11.2015; publ. 26.05.2017]
  8. Савченко А.А., Борисов А.Г., Модестов А.А., Кудрявцев И.В., Мошев А.В., Гвоздев И.И., Тоначева О.Г. Особенности взаимосвязи фенотипа и хемилюминесцентной активности нейтрофильных гранулоцитов у больных раком почки // Медицинская иммунология. 2016. Т. 18, № 3. С. 259–268. [Savchenko A.A., Borisov A.G., Modestov A.A., Kudryavtsev I.V., Moshev A.V., Gvozdev I.I., Tonacheva O.G. Phenotypic features and chemiluminescent activity of neutrophilic granulocytes in the patients with renal cancer. Meditsinskaya immunologiya = Medical Immunology (Russia), 2016, vol. 18, no. 3, pp. 259–268. doi: 10.15789/1563-0625-2016-3-259-268 (In Russ.)]
  9. Савченко А.А., Борисов А.Г., Модестов А.А., Мошев А.В., Кудрявцев И.В., Тоначева О.Г., Кощеев В.Н. Фенотипический состав и хемилюминесцентная активность моноцитов у больных почечно-клеточным раком // Медицинская иммунология. 2015. Т. 17. № 2. С. 141–150. [Savchenko A.A., Borisov A.G., Modestov A.A., Moshev A.V., Kudryavtsev I.V., Tonacheva O.G., Koshcheev V.N. Monocytes subpopulations and chemiluminescent activity in patients with renal cell carcinoma. Meditsinskaya immunologiya = Medical Immunology (Russia), 2015, vol. 17, no. 2, pp. 141–150. doi: 10.15789/1563-0625-2015-2-141-150 (In Russ.)]
  10. Савченко А.А., Здзитовецкий Д.Э., Борисов А.Г. Иммунометаболические нарушения при распространенном гнойном перитоните. Новосибирск: Наука, 2013. 142 с. [Savchenko A.A., Zdzitoveckij D.E., Borisov A.G. The immune and metabolic disorders by the widespread purulent peritonitis. Novosibirsk: Nauka, 2013. 142 p.]
  11. Савченко А.А., Здзитовецкий Д.Э., Борисов А.Г., Лузан Н.А. Хемилюминесцентная активность нейтрофильных гранулоцитов и уровни концентрации цитокинов у больных распространенным гнойным перитонитом // Цитокины и воспаление. 2013. Т. 12, № 1–2. С. 115–119. [Savchenko A.A., Zdzitovetskiy D.E., Borisov A.G., Luzan N.A. Neutrophil chemiluminescent activity and cytokine concentration levels in patients with extensive purulent peritonitis. Tsitokiny i vospalenie = Cytokines and Inflammation, 2013, vol. 12, no. 1–2, pp. 115–119. (In Russ.)]
  12. Смирнова О.В., Титова Н.М., Каспаров Э.В., Елманова Н.Г. Хемилюминесцентная активность нейтрофильных гранулоцитов в прогрессировании механической желтухи в зависимости от уровня билирубина и генеза желтухи // Медицинская иммунология. 2016. Т. 18, № 3. С. 269–278. [Smirnova O.V., Titova N.M., Kasparov E.W., Yelmanova N.G. Chemiluminescent activity of neutrophilic granulocytes in progression of obstructive jaundice depending on its origin and bilirubin levels. Meditsinskaya immunologiya = Medical Immunology (Russia), 2016, vol. 18, no. 3, pp. 269–278. doi: 10.15789/1563-0625-2016-3-269-278 (In Russ.)]
  13. Черешнев В.А., Шмагель К.В. Иммунология. М.: Магистр-Пресс, 2013. 448 с. [Chereshnev V.A., Shmagel’ K.V. Immunologiya [Immunology]. Moscow: Magistr-Press, 2013. 448 p.]
  14. Allen R.C. Neutrophil leukocyte: combustive microbicidal action and chemiluminescence. J. Immunol. Res., 2015, vol. 2015, 11 p. doi: 10.1155/2015/794072
  15. Aranda A., Sequedo L., Tolosa L., Quintas G., Burello E., Castell J.V., Gombau L. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay: a quantitative method for oxidative stress assessment of nanoparticle-treated cells. Toxicol. In Vitro, 2013, vol. 27, iss. 2, pp. 954–963. doi: 10.1016/j.tiv.2013.01.016
  16. Back P., Matthijssens F., Vanfleteren J.R., Braeckman B.P. A simplified hydroethidine method for fast and accurate detection of superoxide production in isolated mitochondria. Anal. Biochem., 2012, vol. 423, no 1, pp. 147–151. doi: 10.1016/j.ab.2012.01.008
  17. Beutler B. Innate immunity: an overview. Mol. Immunol., 2004, vol. 40, iss. 12, pp. 845–859. doi: 10.1016/j.molimm.2003.10.005
  18. Broxton C.N., Culotta V.C. SOD enzymes and microbial pathogens: surviving the oxidative storm of infection. PLoS Pathog., 2016, vol. 12, no. 1: e1005295. doi: 10.1371/journal.ppat.1005295
  19. Chae C.S., Teran-Cabanillas E., Cubillos-Ruiz J.R. Dendritic cell rehab: new strategies to unleash therapeutic immunity in ovarian cancer. Cancer Immunol. Immunother., 2017, vol. 66, iss. 8, pp. 969–977. doi: 10.1007/s00262-017-1958-2
  20. Chio I.I.C., Tuveson D.A. ROS in cancer: the burning question. Trends Mol. Med., 2017, vol. 23, iss. 5, pp. 411–429. doi: 10.1016/j.molmed.2017.03.004
  21. Cooper E.L. From Darwin and Metchnikoff to Burnet and beyond. Contrib. Microbiol., 2008, vol. 15, pp. 1–11. doi: 10.1159/ 000135680
  22. Dehne N., Mora J., Namgaladze D., Weigert A., Brüne B. Cancer cell and macrophage cross-talk in the tumor microenvironment. Curr. Opin. Pharmacol., 2017, vol. 35, pp. 12–19. doi: 10.1016/j.coph.2017.04.007
  23. Dzik J.M. The ancestry and cumulative evolution of immune reactions. Acta Biochim. Pol., 2010, vol. 57, no. 4, pp. 443–466.
  24. Folkes L.K., Patel K.B., Wardman P., Wrona M. Kinetics of reaction of nitrogen dioxide with dihydrorhodamine and the reaction of the dihydrorhodamine radical with oxygen: implications for quantifying peroxynitrite formation in cells. Arch. Biochem. Biophys., 2009, vol. 484, iss. 2, pp. 122–126. doi: 10.1016/j.abb.2008.10.014
  25. Granot Z., Jablonska J. Distinct functions of neutrophil in cancer and its regulation. Mediators Inflamm., 2015, vol. 2015, 11 p. doi: 10.1155/2015/701067
  26. Haselmayer P., Tenzer S., Kwon B.S., Jung G., Schild H., Radsak M.P. Herpes virus entry mediator synergizes with Toll-like receptor mediated neutrophil inflammatory responses. Immunology, 2006, vol. 119, no. 3, pp. 404–411. doi: 10.1111/j.1365-2567.2006.02449.x
  27. Havixbeck J.J., Wong M.E., More Bayona J.A., Barreda D.R. Multi-parametric analysis of phagocyte antimicrobial responses using imaging flow cytometry. J. Immunol. Methods, 2015, vol. 423, pp. 85–92. doi: 10.1016/j.jim.2015.03.016
  28. Hosaka S., Obuki M., Nakajima J., Suzuki M. Comparative study of antioxidants as quenchers or scavengers of reactive oxygen species based on quenching of MCLA-dependent chemiluminescence. Luminescence, 2005, vol. 20, iss. 6, pp. 419–427. doi: 10.1002/bio.867
  29. Ichibangase T., Ohba Y., Kishikawa N., Nakashima K., Kuroda N. Evaluation of lophine derivatives as L-012 (luminol analog)-dependent chemiluminescence enhancers for measuring horseradish peroxidase and H2O2. Luminescence, 2014, vol. 29, iss. 2, pp. 118–121. doi: 10.1002/bio.2513
  30. Kalyanaraman B., Darley-Usmar V., Davies K.J., Dennery P.A., Forman H.J., Grisham M.B., Mann G.E., Moore K., Roberts II L.J., Ischiropoulos H. Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations. Free Radic. Biol. Med., 2012, vol. 52, iss. 1, pp. 1–6. doi: 10.1016/j.freeradbiomed.2011.09.030
  31. Kalyanaraman B., Dranka B.P., Hardy M., Michalski R., Zielonka J. HPLC-based monitoring of products formed from hydro-ethidine-based fluorogenic probes — the ultimate approach for intra- and extracellular superoxide detection. Biochim. Biophys. Acta, 2014, vol. 1840, iss. 2, pp. 739–744. doi: 10.1016/j.bbagen.2013.05.008
  32. Koul M., Kumar A., Deshidi R., Sharma V., Singh R.D., Singh J., Sharma P.R., Shah B.A., Jaglan S., Singh S. Cladosporol A triggers apoptosis sensitivity by ROS-mediated autophagic flux in human breast cancer cells. BMC Cell Biol., 2017, vol. 18, no. 26, 15 p. doi: 10.1186/s12860-017-0141-0
  33. Lyublinskaya O.G., Zenin V.V., Shatrova A.N., Aksenov N.D., Zemelko V.I., Domnina A.P., Litanyuk A.P., Burova E.B., Gubarev S.S., Negulyaev Y.A., Nikolsky N.N. Intracellular oxidation of hydroethidine: compartmentalization and cytotoxicity of oxidation products. Free Radic. Biol. Med., 2014, vol. 75, pp. 60–68. doi: 10.1016/j.freeradbiomed.2014.07.008
  34. Maeda H., Yamamoto K., Nomura Y., Kohno I., Hafsi L., Ueda N., Yoshida S., Fukuda M., Fukuyasu Y., Yamauchi Y., Itoh N. A design of fluorescent probes for superoxide based on a nonredox mechanism. J. Am. Chem. Soc., 2005, vol. 127, no 1, pp. 68–69. doi: 10.1021/ja047018k
  35. Mechnikov I.I. Immunity in infective diseases. By Il’ia Il’ich Mechnikov, 1905. Rev. Infect. Dis., 1988, vol. 10, no 1, pp. 223–227.
  36. Pliyev B.K., Shmidt E.I., Ivanova A.V., Menshikov M. Circulating CD35–/CD49d+ neutrophils in influenza virus infection patients. Hum. Immunol., 2012, vol. 73, no 11, pp. 1087–1090. doi: 10.1016/j.humimm.2012.07.327
  37. Ramanathan S., Jagannathan N. Tumor associated macrophage: a review on the phenotypes, traits and functions. Iran J. Cancer Prev., 2014, vol. 7, no 1, pp. 1–8.
  38. Robinson K.M., Janes M.S., Beckman J.S. The selective detection of mitochondrial superoxide by live cell imaging. Nat. Protoc., 2008, vol. 3, no 6, pp. 941–947. doi: 10.1038/nprot.2008.56
  39. Saengmuang P., Kewcharoenwong C., Tippayawat P., Nithichanon A., Buddhisa S., Lertmemongkolchai G. Effect of host factors on neutrophil functions in response to Burkholderia pseudomallei in healthy Thai subjects. Jpn. J. Infect. Dis., 2014, vol. 67, no 6, pp. 436–440.
  40. Scharn C.R., Collins A.C., Nair V.R., Stamm C.E., Marciano D.K., Graviss E.A., Shiloh M.U. Heme oxygenase-1 regulates inflammation and mycobacterial survival in human macrophages during Mycobacterium tuberculosis infection. J. Immunol., 2016, vol. 196, no 11, pp. 4641–4649. doi: 10.4049/jimmunol.1500434
  41. Sikora J.P., Chlebna-Sokół D., Andrzejewska E., Chrul S., Polakowska E., Wysocka A., Sikora A. Clinical evaluation of pro-inflammatory cytokine inhibitors (sTNFR I, sTNFR II, IL-1 ra), anti-inflammatory cytokines (IL-10, IL-13) and activation of neutrophils after burn-induced inflammation. Scand. J. Immunol., 2008, vol. 68, iss. 2, pp. 145–152. doi: 10.1111/j.1365-3083.2008.02126.x
  42. Sirokmány G., Donkó Á., Geiszt M. Nox/Duox family of NADPH oxidases: lessons from knockout mouse models. Trends Pharmacol. Sci., 2016, vol. 37, iss. 4, pp. 318–327. doi: 10.1016/j.tips.2016.01.006
  43. Talib J., Maghzal G.J., Cheng D., Stocker R. Detailed protocol to assess in vivo and ex vivo myeloperoxidase activity in mouse models of vascular inflammation and disease using hydroethidine. Free Radic. Biol. Med., 2016, vol. 97, pp. 124–135. doi: 10.1016/j.freeradbiomed.2016.05.004
  44. Tripathi S., Wang G., White M., Rynkiewicz M., Seaton B., Hartshorn K. Identifying the critical domain of LL-37 involved in mediating neutrophil activation in the presence of influenza virus: functional and structural analysis. PLoS One, 2015, vol. 10, no 8:e0133454. doi: 10.1371/journal.pone.0133454
  45. Vowells S.J., Sekhsaria S., Malech H.L., Shalit M., Fleisher T.A. Flow cytometric analysis of the granulocyte respiratory burst: a comparison study of fluorescent probes. J. Immunol. Methods, 1995, vol. 178, no 1, pp. 89–97.
  46. Wang J., Xu M., Chen M., Jiang Z., Chen G. Study on sonodynamic activity of metallophthalocyanine sonosensitizers based on the sonochemiluminescence of MCLA. Ultrason. Sonochem., 2012, vol. 19, no 2, pp. 237–242. doi: 10.1016/j.ultsonch.2011.06.021
  47. Wang Y., Wang W., Xu H., Sun Y., Sun J., Jiang Y., Yao J., Tian Y. Non-lethal sonodynamic therapy inhibits atherosclerotic plaque progression in apoE-/- mice and attenuates ox-LDL-mediated macrophage impairment by inducing heme oxygenase-1. Cell Physiol. Biochem., 2017, vol. 41, no. 6, pp. 2432–2446. doi: 10.1159/000475913
  48. Wardman P. Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: progress, pitfalls, and prospects. Free Radic. Biol. Med., 2007, vol. 43, iss. 7, pp. 995–1022. doi: 10.1016/j.freeradbiomed.2007.06.026
  49. Wardman P. Methods to measure the reactivity of peroxynitrite-derived oxidants toward reduced fluoresceins and rhodamines. Methods Enzymol., 2008, vol. 441, pp. 261–282. doi: 10.1016/S0076-6879(08)01214-7
  50. Zielonka J., Kalyanaraman B. Hydroethidine- and mitoSOX-derived red fluorescence is not a reliable indicator of intracellular superoxide formation: another inconvenient truth. Free Radic. Biol. Med., 2010, vol. 48, iss. 8, pp. 983–1001. doi: 10.1016/j.freeradbiomed.2010.01.028
  51. Zielonka J., Lambeth J.D., Kalyanaraman B. On the use of L-012, a luminol-based chemiluminescent probe, for detecting su-peroxide and identifying inhibitors of NADPH oxidase: a reevaluation. Free Radic. Biol. Med., 2013, vol. 65, pp. 1310–1314. doi: 10.1016/j.freeradbiomed.2013.09.017

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