Histopathological Changes of Heart, Liver, and Duodenum in Iron Overload: Comparing the Role of Quercetin with Deferoxamine
Article Sidebar
Main Article Content
Abstract
The aim of this study was to perform a comparison between quercetin and deferoxamine (DFO) on the heart, liver, and duodenum in iron overloaded rabbits. Four groups of adult rabbits (each of seven) used in the current study were treated as follows for 28 days: control (C): were injected intraperitoneally (IP) normal saline every 72 hours + normal saline orally daily. T1, T2, and T3 groups were IP injected with iron dextran 100 mg/kg every 72 hours, T1 was left without treatment, group T2 was administrated with quercetin 350 mg/kg orally daily, and group T3 was injected with DFO 125 mg/kg intramuscularly (IM) daily. At the end of experiment, all animals were sacrificed, and tissue specimens were collected from the heart, liver, and duodenum for histopathological study. The results of T1 group showed edema, and iron deposition between the myocardial cells. The T2 group showed slight edema between the myocardium. T3 group showed edema, thickening, and congestion of blood vessels, all groups showed a positive result of the Prussian blue stain (PBS) compared to the control. The liver sections for the T1 group revealed iron overload, fibrosis, and hepatocyte necrosis. T2 and T3 groups showed mild vacuolation of hepatocytes, a decrease in iron overload, and these groups showed a positive result of the PBS compared to the control. Duodenum sections for T1 group showed hemochromatosis. while T2 group showed mild iron deposition. Positive result of PBS in T1 and T3 compared to the T2 and control were observed. Conclusion: Quercetin mitigates histological changes in iron overloaded rabbits due to its properties as an iron chelating agent compared to DFO.
Received: 2 August 2023
Accepted: 23 October 2023
Published: 28 December 2023
Downloads
Article Details
How to Cite
References
Abbaspour N, Hurrell R, Kelishadi R. Review on iron and its importance for human health. J Res Med Sci. 2014;19(2):164.
Fleming RE, Ponka P. Iron overload in human disease. N Engl J Med. 2012;366(4):348-359. DOI: 10.1056/NEJMra1004967.
Hsu CC, Senussi NH, Fertrin KY, Kowdley KV. Iron overload disorders. Hepatol Commun. 2022;6(8):1842-1854. DOI: 10.1002/hep4.2012
Hamed S, Al-Qayim MA. Protective Role of Propolis against Iron Overload Induced Genotoxicity and Oxidant/Antioxidant Status. J Global Pharma Technol. 2019;11(5):628-635.
Yas AM. 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. DOI: 10.1080/07853890.2022.2028894
Galaris D, Barbouti A, Pantopoulos K. Iron homeostasis and oxidative stress: An intimate relationship. Biochim Biophys Acta Mol Cell Res. 2019;1866(12):118535. DOI: 10.1016/j.bbamcr.2019.118535
Milic S, Mikolasevic I, Orlic L, Devcic E, Starcevic-Cizmarevic N, Stimac D, Ristic S. The role of iron and iron overload in chronic liver disease. Med Sci Monit. 2016;22:2144. DOI: 10.12659/msm.896494.
Camiolo G, Tibullo D, Giallongo C, Romano A, Parrinello NL, Musumeci G, Palumbo GA. α-Lipoic acid reduces iron-induced toxicity and oxidative stress in a model of iron overload. Int J Mol Sci. 2019;20(3):609. DOI: 10.3390/ijms20030609
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. DOI: 10.1080/07853890.2022.2028894
Musallam KM, Angastiniotis M, Eleftheriou A, Porter JB. Cross-talk between available guidelines for the management of patients with beta-thalassemia major. Acta Haematol. 2013;130(2):64-73. DOI: 10.1159/000345734
Tantiworawit A, Chattipakorn SC, Chattipakorn N. Current and Future Treatments of Iron Overload in Thalassemia Patients. In: Atta-ur-Rahman, editor. Frontiers in Clinical Drug Research-Hematology: Volume 5. Sharjah: Bentham Science Publishers; 2022. p. 90-132. doi: 10.2174/9789815039535122050005 .
Velasquez J, Wray AA. Deferoxamine. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [updated 2023 May 22; cited 2023 Jun 29]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557654/
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
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.
Khalil LW, Layla Hashim Alol LH, Obead AL. Effect of crude polyphenol extracted from black olive fruit (olea europae) on some physiological and immunological parameters in males rats treated with hydrogen peroxide: Iraqi J. Vet. Med. 2013;37(1):83-89. DOI: https://DOI.org/10.30539/iraqijvm.v37i1.337
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. DOI:10.20959/wjpr201611-7193
HK ES, Mohammed ZA, Ahmed MM. Ameliorative role of quercetin in iron overload induced heart and brain toxicity in adult male albino rats. J Toxicol Enviro Health Sci. 2019;11(2):16-26. DOI: 10.5897/JTEHS2019.0429
Chen X, Li H, Wang Z, Zhou Q, Chen S, Yang B, He M. Quercetin protects the vascular endothelium against iron overload damages via ROS/ADMA/DDAHⅡ/eNOS/NO pathway. Eur J Pharmacol. 2020;868:172885. DOI: 10.1016/j.ejphar.2019.172885
El-Sheikh AA, Ameen SH, AbdEl-Fatah SS. Ameliorating iron overload in intestinal tissue of adult male rats: quercetin vs deferoxamine. J Toxicol. 2018;2018:8023840. DOI: 10.1155/2018/8023840.
Suvarna KS, Layton C, Bancroft JD. Bancroft's theory and practice of histological techniques E-Book. Elsevier Health Sciences; 2018.
Jouihan NH. Iron-Prussian blue reaction-Mallory’s method. Bio-protocol. 2012;2(13):e222-e222. DOI:10.21769/BioProtoc.222
Galaris D, Barbouti A, Pantopoulos K. Iron homeostasis and oxidative stress: An intimate relationship. Biochim Biophys Acta Mol Cell Res. 2019;1866(12):118535. DOI: 10.1016/j.bbamcr.2019.118535.
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. DOI: doi.org/10.30539/iraqijvm.v42i2.287
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 Phytomedicine. 2017;7(6):542.
Alikhani M, Aalikhani M, Khalili M. Reduction of iron toxicity in the heart of iron-overloaded mice with natural compounds. Eur J Pharmacol. 2022;924:174981. DOI: 10.1016/j.ejphar.2022.174981
Gammella E, Recalcati S, Cairo G. Dual role of ROS as signal and stress agents: iron tips the balance in favor of toxic effects. Oxid Med Cell Longev. 2016;2016:1-14.
Kim BY, Han MJ, Chung AS. Effects of reactive oxygen species on proliferation of Chinese hamster lung fibroblast (V79) cells. Free Radic Biol Med. 2001;30(6):686-698. DOI: 10.1016/S0891-5849(00)00514-1.
Kremastinos DT, Farmakis D, Aessopos A, Hahalis G, Hamodraka E, Tsiapras D, Keren A. β-thalassemia cardiomyopathy: history, present considerations, and future perspectives. Circ Heart Fail. 2010;3(3):451-458. DOI: 10.1161/CIRCHEARTFAILURE.109.913863.
Sukumaran A, Chang J, Han M, Mintri S, Khaw BA, Kim J. Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis. Sci Rep. 2017;7(1):1-10. DOI: 10.1038/s41598-017-05810-2.
Holden P, Nair LS. Deferoxamine: an angiogenic and antioxidant molecule for tissue regeneration. Tissue Eng Part B Rev. 2019;25(6):461-470.
Yatmark P, Morales NP, Chaisri U, Wichaiyo S, Hemstapat W, Srichairatanakool S, Fucharoen S. Iron distribution and histopathological characterization of the liver and heart of β-thalassemic mice with parenteral iron overload: Effects of deferoxamine and deferiprone. Exp Toxicol Pathol. 2014;66(7):333-343. DOI: 10.1016/j.etp.2014.03.002.
Kartikasari AE, Georgiou NA, Visseren FL, van Kats-Renaud H, van Asbeck BS, Marx JJ. Intracellular labile iron modulates adhesion of human monocytes to human endothelial cells. Arterioscler Thromb Vasc Biol. 2004;24(12):2257-2262. DOI: 10.1161/01.ATV.0000147406.00871.b3.
Uranga RM, Salvador GA. Unraveling the burden of iron in neurodegeneration: intersections with amyloid beta peptide pathology. Oxid Med Cell Longev. 2018;2018:1-10. DOI: 10.1155/2018/2850341.
Zimmermann MB, Chassard C, Rohner F, N'goran EK, Nindjin C, Dostal A, Hurrell RF. The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire. Am J Clin Nutr. 2010;92(6):1406-1415. DOI: 10.3945/ajcn.110.004564.
Aziz ES, Khudair KK. Ameliorative Role of Quercetin on Intestinal Hitomorpometric, Oxidative Status and Pro-Inflammatory Changes in Hydrogen Peroxide–Exposed Rats. Plant Archivesss. 2021;21(1):348-356. DOI: 10.51470/PLANTARCHIVES.2021.v21.S1.056
Abood HM, Al-Okialy BN. Effect of green tea (Camellia sinensis) on acrylamide induced cardiac toxicity in adult Wistar rats. Online J Vet Res. 2019;23(6):522-543.
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;9:685364. DOI: 10.3389/fcell.2021.685364.
Mancardi D, Mezzanotte M, Arrigo E, Barinotti A, Roetto A. Iron overload, oxidative stress, and ferroptosis in the failing heart and liver. Antioxidants. 2021;10(12):1864. DOI: 10.3390/antiox10121864.
Wood JC, Otto-Duessel M, Gonzalez I, Aguilar MI, Shimada H, Nick H, Moats R. Deferasirox and deferiprone remove cardiac iron in the iron-overloaded gerbil. Transl Res. 2006;148(5):272-280.
Kontoghiorghes GJ, Neocleous K, Kolnagou A. Benefits and risks of deferiprone in iron overload in thalassaemia and other conditions. Drug Saf. 2003;26(8):553-584. DOI: 10.2165/00002018-200326080-00003.
Pietrangelo A. Iron and the liver. Liver Int. 2016;36:116-123. DOI: 10.1111/liv.13020.
Lesjak M, Hoque R, Balesaria S, Skinner V, Debnam ES, Srai SK, Sharp PA. Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro. PLoS One. 2014;9(7):e102900. DOI: 10.1371/journal.pone.0102900.
Zhao L, Yang N, Song Y, Si H, Qin Q, Guo Z. Effect of iron overload on endothelial cell calcification and its mechanism. Ann Transl Med. 2021;9(22):1721-1721. DOI: 10.21037/atm-21-5666.
Baccan MM, Chiarelli-Neto O, Pereira RMS, Espósito BP. Quercetin as a shuttle for labile iron. J Inorg Biochem. 2012;107(1):34-39. DOI: 10.1016/j.jinorgbio.2011.11.014.