Antioxidant Safety and Antioxidant-induced Stress

Öz

The safe use of antioxidants and reliable antioxidant applications are a new and important area of debate that has been continuing for decades. Today, antioxidant plants, phytochemicals and products are the most popular supplements. Most of them are sold without a prescription, even though they are used like a medicine. We know many scientific reports on the benefits of antioxidants but there are also studies that question whether antioxidant products have harmful effects. Nowadays antioxidant safety is the one of the most important medical topics at oxidant-antioxidant balance and oxidative stress. A physiological balance exists between oxidants and antioxidants in the organism only when both of the forces are present. Studies which document that antioxidant supplementation, inhibits the reactions and effects of free radicals are common. But, it is still unclear which exogen antioxidants and doses should be used to have an efective defense and also what safe limit is for use. It is possible that many of antioxidant phytochemicals and supplements can cause harmful changes in tissues by initiating different mechanisms. The most important question related to the use of antioxidants and antioxidant safety is the names, amounts, kinds and forms of them. The term antioxidative stress is a new strategic word on oxidant-antioxidant balance as like as oxidative stress. Antioxidants may cause stress in tisssues which refers to antioxidative stress. An extraordinary attention on antioxidative stress is a necessity for today's medical disciplines. The further studies are needed to clarify the harmful effects of antioxidants and antioxidative stress for the antioxidant safety. We aimed to focuse on the antioxidant-induced stress. For this reason, some reports on the harmful effects of antioxidants have been discussed in this paper.

Anahtar Kelimeler

• antioxidative stress,harmful effects of antioxidants,antioxidant safety

Antioksidan Güvenliği ve Antioksidan Kaynaklı Stres

Öz

Antioksidanların güvenli kullanımı ve güvenilir antioksidan uygulamaları, on yıllar boyu devam edecek yeni ve önemli bir tartışma alanıdır. Günümüzde antioksidan bitkiler, fitokimyasallar ve antioksidan ürünler en popüler tıbbi ürünlerdir. Büyük çoğunluğu ilaç gibi kullanılmasına rağmen bu ürünler reçetesiz satılır. Antioksidanların yararları hakkında birçok bilimsel rapor biliyoruz, ancak olası zararlı etkilerini sorgulayan araştırmalar ve önemli raporlar da mevcuttur. Aslında antioksidan güvenliği, oksidan-antioksidan denge açısından çok önemlidir. Organizmadaki oksidanlar ve antioksidanlar arasındaki fizyolojik denge, bu kuvvetlerin her ikisi de geçerli olduğunda dengelenir. Antioksidan takviyesinin serbest radikal ürünleri, reaksiyonları ve etkilerini engellediğini belgeleyen çalışmalar yaygındır. Ancak, etkili bir antioksidan savunmaya sahip olmak için hangi ajanların ve hangi miktarların gerekli olduğu ve hangi dozun kullanım için güvenli limiti yansıttığı hala bilinmemektedir. Ekzojen antioksidan fitokimyasalların ve eklerin çoğu, farklı mekanizmalar başlatarak dokularda zararlı değişikliklere neden olabilir. Antioksidan kullanımı ile ilgili en önemli nokta, antioksidan güvenliği için bunların çeşitleri, formları ve dozlarıdır. Antioksidatif stres terimi oksidatif stres gibi oksidan-antioksidan dengesinde yeni bir stratejik kelimedir. Antioksidanlar, dokuları antioksidatif stres olarak adlandırılan strese yönlendirebilir. Olağanüstü bir dikkat ve antioksidan strese odaklanmak, bugünün medikal disiplinleri için bir zorunluluktur. Antioksidan güvenlik için antioksidan ve antioksidan stresin zararlı etkilerini aydınlatmak için daha ileri çalışmalara ihtiyaç olduğunu düşünüyoruz. Bu derlemenin amacı antioksidan kaynaklı strese odaklanmaktır, bu nedenle bu çalışmada antioksidanların zararlı etkileri hakkındaki mevcut kanıtlar analiz edilmiştir.

Anahtar Kelimeler

• Antioksidan güvenliği,antioksidatif stres,antioksidanların zararlı etkileri

Kaynakça

1. Aslan R, Şekeroğlu MR, Tarakçıoğlu M, Bayıroğlu F, Meral İ. Effect Of Acute And Regular Exercise On Antioxidative Enzymes, Tissue Damage Markers And Membran Lipid Peroxidation of Erythrocytes in Sedentary Students. Turkish Journal of Medical Science 1998; 4(28): 411-15.
2. Aslan R, Dündar Y. Nitric Oxide as a Biophysiological Component and a Radical Metabolite. Hayvancılık Araştırma Dergisi 1998; 8(1-2): 34-38.
3. Aslan R. Homeostatik Mekanizmanın Korunması ve Sağaltımda Antioksidanlar. İlaç ve Tedavi Dergisi 1999; 12(8): 475-480.
4. Azam S, Hadi N, Khan NU, Hadi SM. Prooxidant property of green tea polyphenols epicatechin and epigallocatechin-3-gallate: implications for anticancer properties. Toxicology. 2004;18: 555-61.
5. Cheung MC, Zhao XQ, Chait A, Albers JJ, Brown BG. Antioxidant supplements block the response of hdl to simvastatin-niacin therapy in patients with coronary artery disease and low hdl. Arterioscler Thromb Vasc Biol. 2001; 21: 1320-1326.
6. Childs A, Jacobs C, Kaminski T, Halliwell B, Leeuwenburgh C. Supplementation with vitamin c and n-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. Free Radic. Biol Med. 2001; 31: 745-753.
7. Clarkson PM. Antioxidants and physical performance. Critical Reviews in Food and Nutrition. 1995; 35(1-2): 131-141.
8. Çevik C, Aslan R. Effects of photoperiod variations and alpha-lipoic acid treatment on melatonin, cortisol, and oxidative stress levels in the blood of rats. Turk J Biol 2015; 39: 941-949.

9. Dündar Y, Aslan R. Antioxidative stress. Eastern J Med. 2000; 5: 45-47.
10. Evcimen M, Aslan R, Gulay MS. Protective effects of polydatin and grape seed extract in rats exposed to cadmium. Drug and Chemical Toxicology June 2018; DOI:10.1080/01480545.2018.1480629
11. 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: 924–932.
12. Halliwell B, Gutteridge JM. The definition and measurement of antioxidants in biological systems. Free Radic Biol Med. 1995; 18: 125–126.
13. Halliwell B. Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies? Arch Biochem Biophys. 2008; 476: 107-112.
14. Halliwell B. The wanderings of a free radical. Free Radic Biol Med. 2009; 46: 531-542.
15. Herbert V. Viewpoint does mega-C do more good than harm, or more harm than good? Nutrition Today 1993; 28: 126-33.
16. Ji LL. Modulation of skeletal muscle antioxidant defense by exercise: Role of redox signaling. Free Radic Biol Med. 2008; 44: 142-152.
17. Lakshman MR. Alpha and omega of carotenoid cleavage. J Nutr. 2004; 134:241S-245S.
18. Martin HD, Ruck C, Schmidt M, Sell S, Beutner S, Mayer B, Walsh R. Chemistry of carotenoid oxidation and free radical reactions. Pure Appl Chem. 1999; 71: 2253-2262.
19. McCord JM, Keele BB, Fridovich I. An enzyme-based theory of obligate anaerobiosis: The physiological function of superoxide dismutase. Proc Natl Acad Sci. 1971; 68: 1024-1027.
20. Munik MS, Ekmekcioğlu C. Prooxidant effects of melatonin: a brief review. Turk J Biol. 2015; 39: 832-839.
21. Narwaley M, Michail K, Arvadia P, Siraki AG. Drug-induced protein free radical formation is attenuated by unsaturated fatty acids by scavenging drug-derived phenyl radical metabolites. Chem Res Toxicol. 2011; 24: 1031-1039.
22. Niki E. Vitamin C as an antioxidant. Vitamins, Minerals, and Functional Consequences of Maternal Malnutrition. World Res. Nutr. Diet. Basel Karger. 1991; 64: 4-30.
23. Pechanova O, Simko F. Chronic antioxidant therapy fails to ameliorate hypertension: Potential mechanisms behind. J Hypertens. 2009; 27: 32-36.
24. Poljsak B, Gazdag Z, Jenko-Brinovec S, Fujs S, Pesti M, Belagyi J, Plesnicar S, Raspor P. Pro-oxidative vs antioxidative properties of ascorbic acid in chromium-induced damage: An in vivo and in vitro approach. J Appl Toxicol. 2005; 25: 535-548.
25. Poljsak B, Milisav I. The Neglected Significance of “Antioxidative Stress” Oxidative Medicine and Cellular Longevity. 2012; P:1-12 doi:10.1155/2012/480895
26. Ristow M, Zarse K, Oberbach A, Kloting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Bluher M. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci. 2009; 106: 8665-8670.
27. Robaszkiewicz A, Balcerczyk A, Bartosz G. Antioxidative and prooxidative effects of quercetin on A549 cells. Cell biology international 2007; 31: 1245-50.
28. Sevanian A, Davies KJ, Hochstein P. Serum urate as an antioxidant for ascorbic acid. Am J Clin Nutr. 1991; 54: 1129S-1134S.
29. Ward NC, Hodgson JM, Croft KD, Burke V, Beilin LJ, Puddey IB. The combination of vitamin c and grape seed polyphenols increases blood pressure: A randomized, double blind, placebo controlled trial. J Hypertens. 2005; 23: 427-434.
30. Witting LA. Vitamin E and lipid antioxidants in free radical-initiated reactions. In Priyor A (ed) Free radicals in biology. IV. New York Academic Press. 1980; 295-319.
31. Villanueva C, Kross RD. Antioxidant-Induced Stress. Int J Mol Sci. 2012; 13(2); 2091-109.
32. Yen GC, Duh PD, Tsai HL, Huang SL. Pro-oxidative properties of flavonoids in human lymphocytes. Bioscience Biotechnology and Biochemistry. 2003; 67: 1215-22.
33. Yeum KJ, Aldini G, Russell RM, Krinsky NI. Antioxidant/pro-oxidant Actions of Carotenoids. In Carotenoids. Birkhäuser Verlag: Basel, Switzerland. 2009; 5: 235-268.