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Strategies to Target Mitochondria and Oxidative Stress by Antioxidants: Key Points and Perspectives

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ABSTRACT

For several decades, many antioxidants studies have emphasized the marked disparity between the beneficial effect of the antioxidants shown in preclinical studies and their inability to show beneficial effects in clinical trials. Besides, it is not uncommon to find highly contradictory clinical results, which may explain why consumers are less enthusiastic for antioxidant uses. This perspective article aims to highlights the critical role of Reactive Oxygen Species (ROS) and antioxidants, the potential mechanisms that might account for these discrepancies in clinical trials and some strategies to target oxidative stress and mitochondria by antioxidants. We need urgently to set up standard methods to evaluate antioxidants and oxidative stress in human and in particular at mitochondria level. The determination of what the basal level of ROS is in normal human may be used to identify pathologic ROS levels in patients and ultimately guide antioxidants treatment.

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REFERENCES

  1. Halliwell B. Oxygen radicals: a commonsense look at their nature and medical importance. Med Biol. 1984;62(2):71-77.

    PubMed  CAS  Google Scholar 

  2. Halliwell B. The wanderings of free radicals. Free Radic Biol Med. 2009;46:531-542.

    Article  PubMed  CAS  Google Scholar 

  3. McCord JM, Edeas MA. SOD, oxidative stress and human pathologies: a brief history and a future vision. Biomed Pharmacother. 2005;59(4):139-42.

    Article  PubMed  CAS  Google Scholar 

  4. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44-84.

    Article  PubMed  CAS  Google Scholar 

  5. Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Rad Biol Med. 2000;29(3-4):222-230.

    Article  PubMed  CAS  Google Scholar 

  6. Piotrowski WJ, Marczak J. Cellular sources of oxidants in the lung. Int J Occup Med Environ Health. 2000;13(4):369-385.

    PubMed  CAS  Google Scholar 

  7. Rammal H, Bouayed J, Soulimani R. A direct relationship between aggressive behavior in the resident/intruder test and cell oxidative status in adult male mice. Eur J Pharmacol. 2010;627(1-3):173-176.

    Article  PubMed  CAS  Google Scholar 

  8. Van Heerebeek L, Meischl C, Stooker W, Meijer CJ, Niessen HW, Roos D. NADPH oxidase(s): new source(s) of reactive oxygen species in the vascular system? J Clin Pathol. 2002;55(8):561-568.

    Article  PubMed  Google Scholar 

  9. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res. 2000;86(5):494-501.

    PubMed  CAS  Google Scholar 

  10. Omura T. Forty years of cytochrome P450. Biochem Biophys Res Commun. 1999;266(3):690-698.

    Article  PubMed  CAS  Google Scholar 

  11. Klebanoff SJ. Myeloperoxidase: friend and foe. J Leukoc Biol. 2005;77(5):598-625.

    Article  PubMed  CAS  Google Scholar 

  12. Gizi A, Papassotiriou I, Apostolakou F, et al. Assessment of oxidative stress in patients with sickle cell disease: The glutathione system and the oxidant-antioxidant status. Blood Cells Mol Dis. 2007;46(3):220-225.

    Article  Google Scholar 

  13. Trinei M, Giorgio M, Cicalese A, Barozzi S, Ventura A, Migliaccio E, et al. A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis. Oncogene. 2002;21(24):3872-78.

    Article  PubMed  CAS  Google Scholar 

  14. Edeas M. Antioxidants, Controversies and Perspectives: How to explain the failure of clinical studies using antioxidants? J Soc Biol. 2009;203(3):271-80.

    Article  PubMed  CAS  Google Scholar 

  15. Grune T. Oxidants and antioxidative defense. Hum Exp Toxicol. 2002;21(2):61-62.

    Article  PubMed  CAS  Google Scholar 

  16. Misciagna G, De Michele G, Trevisan M. Non enzymatic glycated proteins in the blood and cardiovascular disease. Curr Pharm Des. 2007;13(36):3688-95.

    Article  PubMed  CAS  Google Scholar 

  17. Ravelojaona V, Péterszegi G, Molinari J, Gesztesi JL, Robert L. Demonstration of the cytotoxic effect of Advanced Glycation Endproducts (AGE-s). J Soc Biol. 2007;201(2):185-8.

    Article  PubMed  CAS  Google Scholar 

  18. Wang AL, Yu A, Qi H, Zhu XA, Tso M. AGEs mediated expression and secretion of TNF alpha in rat retinal microglia. Exp Eye Res. 2007;84(5):905-913.

    Article  PubMed  CAS  Google Scholar 

  19. Martin KR, Barrett JC. Reactive oxygen species as double-edged swords in cellular processes: low-dose cell signaling versus high-dose toxicity. Hum Exp Toxicol. 2002;21(2):71-75.

    Article  PubMed  CAS  Google Scholar 

  20. Sarmadi BH, Ismail A. Antioxidative peptides from food proteins: a review. Peptides. 2010;31(10):1949-1956.

    Article  PubMed  CAS  Google Scholar 

  21. Sagun KC, Carcamo JM, Golde DW. Vitamin C enters mitochondria via facilitative glucose transporter 1 (Glut1) and confers mitochondrial protection against oxidative injury. FASEB J. 2005;19(12):1657-67.

    Article  CAS  Google Scholar 

  22. Frankel EN, Finley JW. How to standardize the multiplicity of methods to evaluate natural antioxidants. J Agric Food Chem. 2008;56:4901-4908.

    Article  PubMed  CAS  Google Scholar 

  23. Yin H. New techniques to detect oxidative stress markers: mass spectrometry-based methods to detect isoprostanes as the gold standard for oxidative stress in vivo. BioFactors (Oxford, England). 2008;34(2):109-124.

    CAS  Google Scholar 

  24. Sies H. Total antioxidant capacity: Appraisal of a concept. J Nutr. 2007;137:1493-1495.

    PubMed  CAS  Google Scholar 

  25. Bouayed J, Bohn T. Exogenous antioxidants-Double-edged swords in cellular redox state: Health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxid Med Cell Longev. 2010;3(4):228-237.

    Article  PubMed  Google Scholar 

  26. Patel SR, Sigman M. Antioxidant therapy in male infertility. Urol Clin N Am. 2008;35(2):319-330.

    Article  Google Scholar 

  27. Tremellen K. Oxidative stress and male infertility--A clinical perspective. Hum Reprod Update. 2008;14(3):243-258.

    Article  PubMed  CAS  Google Scholar 

  28. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial ROS-induced ROS release: an update and review. Biochim Biophys Acta. 2006;1757(5-6):509-517.

    PubMed  CAS  Google Scholar 

  29. Gutierrez J, Ballinger SW, Darley-Usmar VM, Landar A. Free radicals, mitochondria, and oxidized lipids: the emerging role in signal transduction in vascular cells. Circ Res. 2006;99(9):924-932.

    Article  PubMed  CAS  Google Scholar 

  30. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005;54(6):1615-25.

    Article  PubMed  CAS  Google Scholar 

  31. Yu T, Robotham JL, Yoon Y. Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc Natl Acad Sci USA. 2006;103(8):2653-8.

    Article  PubMed  CAS  Google Scholar 

  32. Green K, Brand MD, Murphy MP. Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Diabetes. 2004;53 Suppl 1:110-8.

    Article  Google Scholar 

  33. Edeas M, Attaf D, Mailfert AS, Nasu M, Joubet R. Maillard reaction, mitochondria and oxidative stress: potential role of antioxidants. Pathol Biol. 2010;58(3):220-225.

    Article  PubMed  CAS  Google Scholar 

  34. Mustata GT, Rosca M, Biemel KM, Reihl O, Smith MA, Viswanathan A, et al. Paradoxical effects of green tea (Camellia sinensis) and antioxidant vitamins in diabetic rats: improved retinopathy and renal mitochondrial defects but deterioration of collagen matrix glycoxidation and cross-linking. Diabetes. 2005;54(2):517-26.

    Article  PubMed  CAS  Google Scholar 

  35. Sheu SS, Nauduri D, Anders MW. Targeting antioxidants to mitochondria: a new therapeutic direction. Biochim Biophys Acta. 2006;1762(2):256-65.

    PubMed  CAS  Google Scholar 

  36. Klings ES, Farber HW. Role of free radicals in the pathogenesis of acute chest syndrome in sickle cell disease. Respir Res. 2001;2(5):280-285.

    Article  PubMed  CAS  Google Scholar 

  37. Metodiewa D, Jaiswal AK, Cenas N, Dickancaite E, Segura-Aguilar J. Quercetin may act as a cytotoxic prooxidant after its metabolic activation to semiquinone and quinoidal product. Free Radic Biol Med. 1999;26:107-116.

    Article  PubMed  CAS  Google Scholar 

  38. Watjen W, Michels G, Steffan B, et al. Low concentrations of flavonoids are protective in rat H4IIE cells whereas high concentrations cause DNA damage and apoptosis. J Nutr. 2005;135(3):525-531.

    PubMed  Google Scholar 

  39. Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Rad Biol Med. 1996;20(7):933-956.

    Article  PubMed  CAS  Google Scholar 

  40. Galati G, Lin A, Sultan AM, O'Brien PJ. Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins. Free Rad Biol Med. 2006;40(4):570-580.

    Article  PubMed  CAS  Google Scholar 

  41. Raza H, John A. Green tea polyphenol epigallocatechin-3-gallate differentially modulates oxidative stress in PC12 cell compartments. Toxicol Appl Pharmacol. 2005;207(3):212-220.

    Article  PubMed  CAS  Google Scholar 

  42. Halliwell B, Gutteridge JM. Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol. 1990;186(1-85).

  43. Akoh CC, Min DB. Food lipids. Chemistry, nutrition and biotechnology.3rd edition. Boca raton:CRC press/Taylor and Francis group [Book]

  44. Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J. Vitamin C exhibits pro-oxidant properties. Nature. 1998;392(6676):559.

    Article  PubMed  CAS  Google Scholar 

  45. Prieme H, Loft S, Nyyssonen K, Salonen JT, Poulsen HE. No effect of supplementation with vitamin E, ascorbic acid, or coenzyme Q10 on oxidative DNA damage estimated by 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion in smokers. Am J Clin Nutr. 1997;65(2):503-507.

    PubMed  CAS  Google Scholar 

  46. Carr AC, Zhu BZ, Frei B. Potential antiatherogenic mechanisms of ascorbate (vitamin C) and alpha-tocopherol (vitamin E). Circ Res. 2000;87(5):349-354.

    PubMed  CAS  Google Scholar 

  47. Farbstein D, Kozak-Blickstein A, Levy AP. Antioxidant vitamins and their use in preventing cardiovascular disease. Molecules (Basel, Switzerland). 2010;15(11):8098-8110.

    CAS  Google Scholar 

  48. Halliwell B. Effect of diet on cancer development: is oxidative DNA damage a biomarker? Free Rad Biol Med. 2002;32(10):968-974.

    Article  PubMed  CAS  Google Scholar 

  49. Lairon D. Intervention studies on Mediterranean diet and cardiovascular risk. Mol Nutr Food Res. 2007;51(10):1209-1214.

    PubMed  CAS  Google Scholar 

  50. Goralczyk R. Beta-carotene and lung cancer in smokers: review of hypotheses and status of research. Nutr Cancer. 2009;61(6):767-774.

    Article  PubMed  CAS  Google Scholar 

  51. Yeh SL, Wang HM, Chen PY, Wu TC. Interactions of beta-carotene and flavonoids on the secretion of pro-inflammatory mediators in an in vitro system. Chem Biol Interact. 2009;179(2-3):386-393.

    Article  PubMed  CAS  Google Scholar 

  52. Leppala JM, Virtamo J, Fogelholm R, et al. Controlled trial of alpha-tocopherol and beta-carotene supplements on stroke incidence and mortality in male smokers. Arterioscler Thromb Vasc Biol. 2000;20(1):230-235.

    Article  PubMed  CAS  Google Scholar 

  53. Tatsuta T, Langer T. Quality control of mitochondria: protection against neurodegeneration and ageing. EMBO J. 2008;27(2):306-314.

    Article  PubMed  CAS  Google Scholar 

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  1. Institute For Antioxidants Applications International Society of Antioxidants in Nutrition and Health (ISANH) Antioxidants Task Force, 15 rue de la paix, 75002, Paris, France

    Marvin Edeas

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  1. Marvin Edeas
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Correspondence to Marvin Edeas.

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Edeas, M. Strategies to Target Mitochondria and Oxidative Stress by Antioxidants: Key Points and Perspectives. Pharm Res 28, 2771–2779 (2011). https://doi.org/10.1007/s11095-011-0587-2

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