Reaction Pathways of Oxidative Transformation of the Radioprotector Quercetin

Quercetin is one of the most promising natural polyphenolic radioprotective compounds. This property is based on its radical-scavenging activity and high antioxidant capacity, in the manifestation of which the products of oxidative degradation of quercetin play a significant role. The formation of specific metabolites during the oxidation of quercetin can determine not only its radioprotective properties, but also toxic manifestations. The purpose of this article is to summarize previously obtained data regarding the reaction pathways of oxidative transformation of quercetin. Materials and methods. We used publicly available scientific publications dedicated to the study of quercetin transformation processes. The method of analysis is descriptive. The discussion of the results. A review of scientific works dedicated to oxygen oxidation, radical-initiated oxidation, electrochemical and enzymatic oxidation is presented, possible transformation products of quercetin and the mechanisms of their formation are given. The most characteristic oxidation pathways of quercetin are determined by the chemical structure of the rings, which exhibit specific reactivity. The influence of the solvent composition on the oxidation products during the autoxidation of quercetin was revealed, while the radical and electrochemical models of oxidation differ in the presence of polymer adducts. Once in a living organism, quercetin can bind free radicals, thereby preventing the harmful effects of radiation, that is, it has the properties of a radioprotector. Conclusions. Quercetin can be considered as a potential radioprotector due to its ability to bind free radicals formed in the biological fluids of living organisms exposed to radiation.

1. Anand David AV, Arulmoli R, Parasuraman S. Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid. Pharmacogn Rev. 2016;10(20):84–9. https://doi.org/10.4103/0973-7847.194044

2. Oboh G, Odubanjo V, Bello F, Ademosun AO, Oyeleye SI, Nwanna Emem EE, Ademiluyi AO. Aqueous extracts of avocado pear (Persea americana Mill.) leaves and seeds exhibit anti-cholinesterases and antioxidant activities in vitro. J Basic Clin Physiol Pharmacol. 2016;27(2):131–40. https://doi.org/10.1515/jbcpp-2015-0049

3. Benković V, Knezević AH, Dikić D, Lisicić D, Orsolić N, Basić I, Kopjar N. Radioprotective effects of quercetin and ethanolic extract of propolis in gamma-irradiated mice. Arh Hig Rada Toksikol. 2009;60(2):129–38. https://doi.org/10.2478/10004-1254-60-2009-1908

4. Patil SL, Mallaiah SH, Patil RK. Antioxidative and radioprotective potential of rutin and quercetin in Swiss albino mice exposed to gamma radiation. J Med Phys. 2013;38(2):87–92. https://doi.org/10.4103/0971-6203.111321

5. Nierenstein M, Whedale M Anthocyanin I. Anthocyanin-like Oxidation Products of Quercetin. Ber Deut Chem Ges. 1912;(44):3487–91.

6. Fuentes J, Atala E, Pastene E, Carrasco-Pozo C, Speisky H. Quercetin Oxidation Paradoxically Enhances its Antioxidant and Cytoprotective Properties. J Agric Food Chem. 2017;65(50):11002–10. https://doi.org/10.1021/acs.jafc.7b05214

7. Zenkevich IG, Eshchenko AY, Makarova SV, Vitenberg AG, Dobryakov YG, Utsal VA. Identification of the products of oxidation of quercetin by air oxygen at ambient temperature. Molecules. 2007;12(3):654–72. https://doi.org/10.3390/12030654

8. Черников ДА, Пальшин ВА, Баженов БН, Сафронов АЮ, Кашевский АВ. Гидроксиацетофеноны – новые модели при изучении электроокисления кверцетина. Известия ВУЗов. Химия и химическая техно- логия. 2012;55(8):43–7. Chernikov DA, Palshin VA, Bazhenov BN, Safronov AYu, Kashevsky AV. Hydroxyacetophenones are new models in the study of quercetin electrooxidation. ChemChemTech [Izv Vyssh Uchebn Zaved Khim Khim Tekhnol]. 2012;55(8):43–7 (In Russian).

9. Makhotkina O, Kilmartin PA. Electrochemical Oxidation of Wine Polyphenols in the Presence of Sulfur Dioxide. J Agric Food Chem. 2013;61(23):5573–81. https://doi.org/10.1021/jf400282z

10. Sokolová R, Degano I, Ramešová S, Bulíčková J, Hromadová M, Gál M, et al. The oxidation mechanism of the antioxidant quercetin in nonaqueous media. Electrochimica Acta. 2011;56(21):7421–7. https://doi.org/10.1016/j.electacta.2011.04.121

11. Cherviakovsky EM, Bolibrukh DA, Baranovsky AV, Vlasova TM, Kurchenko VP, Gilep AA, Usanov SA. Oxidative modification of quercetin by hemeproteins. Biochem Biophys Res Commun. 2006;342(2):459–64. https://doi.org/10.1016/j.bbrc.2006.02.001

12. Takahama U, Hirota S, Nishioka T, Yoshitama K. Oxidation of Quercetin by Salivary Components II. Effects of Quercetin on Reactive Oxygen Metabolism by Salivary Polymorphonuclear Leukocytes. Food Science and Technology Research. 2002;8(3):276–80. https://doi.org/10.3136/fstr.8.276

13. Kubo I, Nihei K, Shimizu K. Oxidation products of quercetin catalyzed by mushroom tyrosinase. Bioorganic Medicinal Chemistry. 2004;12(20):5343–7. https://doi.org/10.1016/j.bmc.2004.07.050

14. Momić T, Savić J, Vasić V. Oxidation of Quercetin by Myeloperoxidase. Research Letters in Physical Chemistry. 2009;2009:614362. https://doi.org/10.1155/2009/614362

15. Takahama U, Oniki T, Hirota S. Oxidation of Quercetin by Salivary Components. I. Salivary Peroxidase- Dependent Oxidation of Quercetin and Characterization of the Oxidation Products. FSTR. 2002;8(2):148–53. https://doi.org/10.1021/jf011697q

16. Зенкевич ИГ, Пушкарева ТИ. О моделировании механизма образования димерных продуктов окисления флафоноидов. Химия растительного сырья. 2018;(3):185–97. https://doi.org/10.14258/jcprm.2018033589 Zenkevich IG, Pushkareva TI. On modeling the mechanism of formation of dimeric oxidation products of flafonoids. Chemistry of plant raw materials. 2018;(3):185–97 (In Russian). https://doi.org/10.14258/jcprm.2018033589

17. Barnes JS., Schug KA. Oxidative Degradation of Quercetin with Hydrogen Peroxide Using Continuous- Flow Kinetic Electrospray–Ion Trap–Time-of-Flight Mass Spectrometry. J Agric Food Chem. 2014;62(19):4322–31. https://doi.org/10.1021/jf500619x

18. Zhou A, Sadik OA. Comparative Analysis of Quercetin Oxidation by Electrochemical, Enzymatic, Autoxidation, and Free Radical Generation Techniques: A Mechanistic Study. J Agric Food Chem. 2008;56(24):12081–91. https://doi.org/10.1021/jf802413v

19. Barnes JS, Foss FW Jr, Schug KA. Thermally Accelerated Oxidative Degradation of Quercetin Using Continuous Flow Kinetic Electrospray-Ion Trap-Time of Flight Mass Spectrometry. J Am Soc Mass Spectrom. 2013;24(10):1513–22. https://doi.org/10.1007/s13361-013-0698-6

20. Krishnamachari V, Levine LH, Paré PW. Flavonoid oxidation by the radical generator AIBN: a unified mechanism for quercetin radical scavenging. J Agric Food Chem. 2002;50(15):4357–63. https://doi.org/10.1021/jf020045e

21. Brown SB, Rajananda V, Holroyd JA, Evans EG. A study of the mechanism of quercetin oxygenation by 18O labelling. A comparison of the mechanism with that of haem degradation. Biochem J. 1982;205(1):239–44. https://doi.org/10.1042/bj2050239

22. Miller E, Schreier P. Studies on flavonol degradation by peroxidase (donor: H2O2-oxidoreductase, EC 1.11.1.7): Part 1–Kaempferol. Food Chemistry. 1985;17(@):143–54. https://doi.org/10.1016/0308-8146(85)90111-6

23. Ramos FA, Takaishi Y, Shirotori M, Kawaguchi Y, Tsuchiya K, Shibata H, et al. Antibacterial and antioxidant activities of quercetin oxidation products from yellow onion (Allium cepa) skin. J Agric Food Chem. 2006;54(10):3551–7. https://doi.org/10.1021/jf060251c