Document Type : Research Paper

Authors

1 Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Baghdad.

2 Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Baghdad

Abstract

    The current study aimed to assess the effective dose of quercetin against iron overload in the adult rabbits by studying the dose response curve through using five successive doses of quercetin on serum iron and total iron binding capacity (TIBC) in iron overload rabbits. Thirty-six of adult male rabbits were used in current study and randomly divided in to the six groups and handled as follows for 28 and 42 days: Control group: rabbits were intraperitoneally (IP) injected with normal saline every 72 hours + normal saline orally each day while rabbits in the T1, T2, T3, T4 and T5 groups were administrated orally quercetin at doses 100,200,300,400 and 500 mg/kg B.W daily respectively and all animal were IP injected with iron dextran at dose of 100 mg/kg every 72 hours. Blood samples were collected after 28 and 42 days from ear vein. The results showed a significant increasing in serum iron of T1 and T2 groups, while T3, T4, and T5 groups not showed any significant difference when compared with control group, while TIBC in T4 and T5 not showed any significant difference when compared with control group after 28 and 42 days of quercetin treatment. Conclusion: As a results, obtained after 28 days of the experiment was used to calculate the ED of quercetin on iron overload which is 350 mg/kg.

Keywords

1. Lynch S, Pfeiffer CM, Georgieff MK, Brittenham G, Fairweather-Tait S, Hurrell RF, et al. Biomarkers of Nutrition for Development (BOND)-iron review. J Nutr. 2018;148(suppl_1):1001S-1067S.https://doi.org/10.1093/jn/nxx036
2. Hamed S, Al-Qayim MA. Protective Role of Propolis against Iron Overload Induced Genotoxicity and Oxidant/Antioxidant Status. J Glob Pharm Technol. 2019;11(5):628-635.
3. Gholampour F, Ghiasabadi FB, Owji SM, Vatanparast J. The protective effect of hydroalcoholic extract of Ginger (Zingiber officinale Rosc.) against iron-induced functional and histological damages in rat liver and kidney. Avicenna J Phytomed. 2017;7(6):542.
4. Alwan MS, Al-Okialy BN. Role of Alpha Lipoic Acid in Oxidant/Antioxidant Status and Gene Expression of Glutathione Reductase in Hydrogen Peroxide Exposed Rats. Iraqi J Vet Med. 2018;42(2):50-57.https://doi.org/10.30539/iraqijvm.v42i2.287
5. Brissot E, Savani BN, Mohty M. Management of high ferritin in long-term survivors after hematopoietic stem cell transplantation. Semin Hematol. 2012;49(1):35-42.https://doi.org/10.1053/j.seminhematol.2011.10.003
6. Yas AMHLS. Iron Overload Estimation by Oral Exfoliative Cytology in Beta Thalassemia Major Patients Undergoing Repeated Blood Transfusion. Indian J Forensic Med Toxicol. 2020;14(1):551-556.
7. Dos Santos L, Bertoli SR, Ávila RA, Marques VB. Iron overload, oxidative stress and vascular dysfunction: Evidences from clinical studies and animal models. Biochim Biophys Acta Gen Subj. 2022;1866(9):130172.https://doi.org/10.1016/j.bbagen.2022.130172
8. Hasan HR, Mahmoud HQ. Iron and its related parameters in serum and saliva of Iraqi patients with non-alcoholic and alcoholic liver disease. MOJ Addict Med Ther. 2018;5(6):249-253.
9. Wu X, Li Y, Zhang S, Zhou X. Ferroptosis as a novel therapeutic target for cardiovascular disease. Theranostics. 2021;11(7):3052.https://doi.org/10.7150/thno.54113
10. Reddy PS, Locke M, Badawy SM. A systematic review of adherence to iron chelation therapy among children and adolescents with thalassemia. Ann Med. 2022;54(1):326-342.https://doi.org/10.1080/07853890.2022.2028894
11. Khudiar KK, Naji NM. Studying the effective dose of polyphenols extracted from green tea in ameliorating the deleterious effect of iron overload in female rats. Iraqi J Vet Med. 2012;36(0E):142-152.https://doi.org/10.30539/iraqijvm.v36i0E.407
12. Al-Jumaily EF, Al-Isawi JK. Chemical composition and antioxidant potential of polyphenol compounds of Cyperus rotundus L. rhizomes. Am J Phytomed Clin Ther. 2014;2(11):1277-1286.
13. Di Petrillo A, Orrù G, Fais A, Fantini MC. Quercetin and its derivates as antiviral potentials: A comprehensive review. Phytother Res. 2022;36(1):266-278.https://doi.org/10.1002/ptr.7309
14. Al-Kubaisi ZA, Al-Shmgani HS, Salman MJ. Evaluation of In vivo and In vitro protective effects of quercetin on Lipopolysaccharide-Induced Inflammation cytotoxicology. Res J Pharm Tech. 2020;13:3897.https://doi.org/10.5958/0974-360X.2020.00690.3
15. Al-Okaily BN. Protective Effect of Alcoholic extract of Black Current in Male Reproductive System of Methionine Overload Rats. Iraqi J Vet Med. 2012;36(2):187-194.https://doi.org/10.30539/iraqijvm.v36i2.494
16. HK ESE, Mohammed ZA, Ahmed MM. Ameliorative role of quercetin in iron overload induced heart and brain toxicity in adult male albino rats. J Toxicol Environ Health Sci. 2019;11(2):16-26.
17. Corrente GA, Malacaria L, Beneduci A, Furia E, Marino T, Mazzone G. Experimental and theoretical study on the coordination properties of quercetin towards aluminum (III), iron (III) and copper (II) in aqueous solution. J Mol Liq. 2021;325:115171.https://doi.org/10.1016/j.molliq.2020.115171
18. Al-Okaily BN, Mohammed RS, Al-Mzain KA, Khudair KK. Effect of Flavonoids Extracted from Black Cumin (Nigella sativa) and Vitamin E in Ameliorating Hepatic Damage Induced by Sodium Nitrate in adult male rats. Iraqi J Vet Med. 2012;36(0E):172-181.https://doi.org/10.30539/iraqijvm.v36i0E.413
19. Chen X, Li H, Wang Z, Zhou Q, Chen S, Yang B, et al. Quercetin protects the vascular endothelium against iron overload damages via ROS/ADMA/DDAHⅡ/eNOS/NO pathway. Eur J Pharmacol. 2020;868:172885.https://doi.org/10.1016/j.ejphar.2019.172885
20. Lu NH, Chen CC, He YJ, Tian R, Xiao Q, Peng YY. Effects of quercetin on hemoglobin-dependent redox reactions: relationship to iron-overload rat liver injury. J Asian Nat Prod Res. 2013;15(12):1265-1276.https://doi.org/10.1080/10286020.2013.838952
21. Baarda DB, de Goede MP, Van Dijkum CJ. Introduction to Statistics with SPSS: A Guide to the Processing, Analysing and Reporting of (research) Data. Routledge; 2019.https://doi.org/10.4324/9781003021704
22. Lemberger L. Log Dose-Response Curves in Basic and Clinical Pharmacology. Dose-Response Relationships in Clinical Pharmacology. 1989. Available from: https://www.esteve.org/wp-content/uploads/2018/01/138167.pdf
23. Hsu CC, Senussi NH, Fertrin KY, Kowdley KV. Iron overload disorders. Hepatol Commun. 2022;6(8):1842-1854.https://doi.org/10.1002/hep4.2012
24. Zhang Y, Gao Z, Liu J, Xu Z. Protective effects of baicalin and quercetin on an iron-overloaded mouse: comparison of liver, kidney and heart tissues. Nat Prod Res. 2011;25(12):1150-1160.https://doi.org/10.1080/14786419.2010.495070
25. Lesjak M, Srai SKS. Role of dietary flavonoids in iron homeostasis. Pharmaceuticals. 2019;12(3):119.https://doi.org/10.3390/ph12030119
26. Perron NR, Brumaghim JL. A review of the antioxidant mechanisms of polyphenol compounds related to iron binding. Cell Biochem Biophys. 2009;53(2):75-100.https://doi.org/10.1007/s12013-009-9043-x
27. Vlachodimitropoulou E, Naftalin RJ, Sharp PA. Quercetin is a substrate for the transmembrane oxidoreductase Dcytb. Free Radic Biol Med. 2010;48(10):1366-1369.https://doi.org/10.1016/j.freeradbiomed.2010.02.021
28. Ahmadi SM, Dehghan G, Hosseinpourfeizi MA, Dolatabadi JEN, Kashanian S. Preparation, characterization, and DNA binding studies of water-soluble quercetin-molybdenum (VI) complex. DNA Cell Biol. 2011;30(7):517-523.https://doi.org/10.1089/dna.2010.1205
29. Lesjak M, Hoque R, Balesaria S, Skinner V, Debnam ES, Srai SKS, et al. Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro. PLoS One. 2014;9(7):e102900.https://doi.org/10.1371/journal.pone.0102900
30. Tang Y, Li Y, Yu H, Gao C, Liu L, Chen S, et al. Quercetin prevents ethanol-induced iron overload by regulating hepcidin through the BMP6/SMAD4 signaling pathway. J Nutr Biochem. 2014;25(6):675-682.https://doi.org/10.1016/j.jnutbio.2014.02.009
31. Lesjak M, Balesaria S, Skinner V, Debnam ES, Srai SKS. Quercetin inhibits intestinal non-haem iron absorption by regulating iron metabolism genes in the tissues. Eur J Nutr. 2019;58(2):743-753.https://doi.org/10.1007/s00394-018-1680-7
32. Hagag AS, Elfaragy MM, Elrifaey S, Abd El-Lateef AE. Therapeutic value of combined therapy with Deferiprone and Silymarin as iron chelators in Egyptian Children with Beta Thalassemia major. Infect Disord Drug Targets. 2015;15(3):189-195.https://doi.org/10.2174/1871526515666150731113305
33. Abotaleb M, Samuel S, Varghese E, Varghese S, Kubatka P, Liskova A, et al. Flavonoids in cancer and apoptosis. Cancers. 2018;11:28.https://doi.org/10.3390/cancers11010028
34. Wang X, Li Y, Han L, Li J, Liu C, Sun C. Role of flavonoids in the treatment of iron overload. Front Cell Dev Biol. 2021;9.https://doi.org/10.3389/fcell.2021.685364
Al-Awady MA, Al-Zamely HA. Effect of quercetin on gene expression of male hormone in adult Wistar rat exposure to the oxidative stress by lead acetate. Al-Qadisiyah J Vet Med Sci. 2016;15(2):47-52.