Alleviation Effects of Diosmetin on H2O2-Induced Oxidative Damage in Human Erythrocytes

Abstract

Free radicals (FRs) are formed in the high amounts result of the metabolic imbalance in cells and tissue. These radicals-induced oxidative damages constitute the basis of many diseases. Organisms have antioxidant defence systems (ADS) to eliminate the destructive effects of the oxidative damage. In addition to these antioxidant systems, dietary flavonoids have the antioxidant effect and the protective role against oxidative damage. In the present study, it was investigated whether a flavonoid derived diosmetin (10, 50, and 100 µM) have the elimination potential on hydrogen peroxide (H2O2)-induced oxidative damage in erythrocyte culture by using biomarkers such as lipid peroxidation (LP) level, catalase (CAT), total superoxide dismutase (SOD) activity and changes of SOD isozymes containing the manganese SOD (Mn SOD) and the cupper-zinc SOD (CuZn SOD). CAT, total SOD, Mn SOD and CuZn SOD activities showed a serious decline with H2O2 treatment, but diosmetin addition significantly increased their activities. While the H2O2 application critically increased LP products in erythrocytes, diosmetin considerably reduced these oxidative damage products. In conclusion, it has been determined that diosmetin can moderate oxidative damage in human erythrocytes by activating or protecting the ADS.

Keywords

• Diosmetin
• Flavonoid
• Oxidative damage
• Human erythrocyte

References

1. Adžić, M., Nićiforović, A., Filipović, D., Vučić, V., Nešković-Konstantinović, Z., & Radojčić, M.B. (2004). Manganese Superoxid Dismutase Level in Blood Cells of Patients with Breast Cancer. Fifth Yugoslav Nuclear Society Conference YUNSC, 391-397.
2. Aebi, H. (1984). Catalase in vitro. Method Enzymol., 105, 121–126. https://doi.org/10.1016/S0076-6879(84)05016-3
3. Alugoju, P.A, Jestadib, D.B., & Periyasamy, L. (2015). Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases. Indian J Clin Biochem., 30(1),11-26. https://doi.org/10.1007/s12291-014-0446-0
4. An, F., Wang, S., Yuan, D., Gong, Y., & Wang, S. (2016). Attenuation of Oxidative Stress of Erythrocytes by Plant-Derived Flavonoids, Orientin and Luteolin. Evid Based Compl Alt., Article ID 3401269, 1-8. https://doi.org/10.1155/2016/3401269
5. Atmaca, E.B., & Aksoy, A. (2009). Oxidative DNA Damage and its Chromatographic Determination. Van Vet. J., 20(2), 79-83.
6. Beauchamp, C., & Fridovich, I. (1971). Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem., 44, 276–287. https://doi.org/10.1016/0003-2697(71)90370-8
7. Becker, L.B. (2003). New concepts in Reactive Oxygen Species and cardiovascular reperfusion physiology. Cardiovasc. Res., 61(3), 461-470. https://doi.org/10.1016/j.cardiores.2003.10.025
8. Brigelius-Flohe, R., & Traber, M. (1999). Vitamin E: Function and metabolism. FASEB J. 13, 1145–55. https://doi.org/10.1096/fasebj.13.10.1145

9. Cemeli, E., Baumgartner, A., & Anderson, D. (2009). Antioxidants and the Comet assay. Mutat Res., 681, 51–67. https://doi.org/10.1016/j.mrrev.2008.05.002
10. Chang, D., Zhang, X., Rong, S., Sha, Q., Liu, P., Han, T., & Pan, H. (2013). Serum Antioxidative Enzymes Levels and Oxidative Stress Products in Age-Related Cataract Patients. Hindawi Publishing Corporation. Oxid Med Cell Longev., 587826. https://doi.org/10.1155/2013/587826
11. Ge, A., Liu, Y., Zeng, X., Kong, H., Ma, Y., Zhang, J., Bai, F., & Huang, M. (2015). Effect of diosmetin on airway remodeling in a murine model of chronic asthma. ABBS, 47(8), 604-611. https://doi.org/10.1093/abbs/gmv052
12. Laemmli, D.K. (1970). Cleavage of structural proteins during in assembly of the heat of bacteriophage T4. Nature, 227, 680. https://doi.org/10.1038/227680a0
13. Libregts, S.F., Gutiérrez, L., de Bruin, A.M., Wensveen, F.M., Papadopoulos, P., van Ijcken, W., Ozgur, Z., Philipsen, S., & Nolte, M.A. (2011). Chronic IFN-γ production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF 1/PU. 1axis. Blood, Hematol Am. Soc., 118(9), 2578 2588. https://doi.org/10.1182/blood-2010-10-315218
14. Memişoğulları, R. (2005). The Role of Free Radıcals and the Effect of Antioxidants in Diabetes. Duzce Med. J., 7(3), 30-39.
15. Mo, G., He, Y., Zhang, X., Lei, X., & Luo, Q. (2020). Diosmetin exerts cardioprotective effect on myocardial ischaemia injury in neonatal rats by decreasing oxidative stress and myocardial apoptosis. Clin Exp Pharmacol Physiol., 1-10. https://doi.org/10.1111/1440-1681.13309
16. Moore, G.E, Gerner, R.E., & Franklin, H.A. (1967). Culture of normal human leukocytes. JAMA. 199(8), 519-524. https://doi.org/10.1001/jama.1967.03120080053007
17. Morabito, R., Romano, O., Spada, G.L., & Marino, A. (2016). H2O2-Induced Oxidative Stress Affects SO4 Transport in Human Erythrocytes. PloS one., 11(1), 1-16. https://doi.org/10.1371/journal.pone.0146485
18. Noroozi, M., Angerson, W.J., & Lean, M.E.J. (1998). Effects of flavonoids and vitamin C on oxidative DNA damage to human lymphocytes. Am. J. Clin. Nutr., 67(6), 1210-1218. https://doi.org/10.1093/ajcn/67.6.1210
19. Özşahin, A.D., Yılmaz, Ö., & Tuzcu, M. (2011). The Protective Role of Composites of Fruit Phenolic on The Occuring of Lipid Peroxidation in Erythrocyte of Rats Sustained Oxidative Stress. F. Ü. Sağ. Bil. Vet. Derg., 25(1), 37-41.
20. Pellegrini, N., Miglio, C., Del Rio, D., Salvatore, S., Serafini, M., & Brighenti, F. (2009). Effect of domestic cooking methods on the total antioxidant capacity of vegetables. Int J Food Sci Nutr., 60(2), 12–22. https://doi.org/10.1080/09637480802175212
21. Ratnam, D.V., Ankola, A.A., Bhardwaj, V., Sahana, D.K., & Kumar, M.N.V.R. (2006). Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective. J. Control Release., 113, 189–207. https://doi.org/10.1016/j.jconrel.2006.04.015
22. Sánchez-Gallego, J.I., López-Revuelta, A., Sardina, J.L., Hernández-Hernández, A., Sánchez-Yagüe, J., & Lianillo, M. (2010). Membrane cholesterol contents modify the protective effects of quercetin and rutin on integrity and cellular viability in oxidized erythrocytes. Free Radic Biol Med, 48(10), 1444-1454. https://doi.org/10.1016/j.freeradbiomed.2010.02.034
23. Schieber, M., & Chandel, N. S. (2014). ROS function in redox signaling and oxidative stress. Curr Bio., 24(10), 453-462.https://doi.org/10.1016/j.cub.2014.03.034
24. Smith, J.E. (1987). Erythrocyte Membrane: Structure, Function and Pathophysiology. Vet. Pathol., 24(6), 471-476. https://doi.org/10.1177/030098588702400601
25. Wang, W., Zhang, S., Yang, F., Xie, J., Chen, J., & Li, Z. (2020). Diosmetin alleviates acute kidney injury by promoting the TUG1/Nrf2/HO-1 pathway in sepsis rats. Int Immunopharmacol., 88, 106965.https://doi.org/10.1016/j.intimp.2020.106965
26. Weydert, C.J., & Cullen, J.J. (2010). Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat. Protoc., 5(1), 51-66. https://doi.org/10.1038/nprot.2009.197
27. Wong, H.W.G., Elwell, J.H., Oberley, L.W., & Goeddel, D.V. (1989). Manganous superoxide dismutase is essential for cellular resistance to cytotoxicity of tumor necrosis factor. Cell, 58, 923-931.https://doi.org/10.1016/0092-8674(89)90944-6
28. Yang, B., Kotani, A., Arai, K., & Kusu, F. (2001). Estimation of the Antioxidant Activities of Flavonoids from Their Oxidation Potentials. Anal. Sci., 17(5), 599-604. https://doi.org/10.2116/analsci.17.599
29. Yang, K., Wei-Fang, L., & Jun-Feng, Y. (2017). Diosmetin Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury in Mice. J. Surg. Res., 214, 69-78. https://doi.org/10.1016/j.jss.2017.02.067
30. Yee, C.D.T., & Liu, T.Z. (1997). Free radical and oxidative damage in human blood cells. J. Biomed Sci., 94, 256-259. https://doi.org/10.1007/BF02253426