Phoenix Dactylifera L. Tree Fruit Exerts Cardioprotective Effect Against DoxorubicinInduced Heart Damage in Rats via Inhibition of Oxidative Stress

Year 2022, Volume: 25 Issue: 2, 193 - 199, 20.08.2022

Reşit Coşkun Aziz İnan Çelik Muharrem Said Coşgun Cihat Dündar Murat Türkoğlu Halis Süleyman

Abstract

Introduction: Phoenix Dactylifera L (PDL) is a fruit containing a rich source of nutrients and bioactive molecules. Doxorubicin is a widely used agent, especially in the treatment of solid cancers. However, cardiotoxicity is one of its most challenging side effects. The present study aimed to investigate the preventive effect of PDL extract against doxorubicin-induced cardiotoxicity.

Patients and Methods: A total of 24 albino Wistar rats were divided into four equal groups. Phoenix Dactylifera L (PDLG) and Phoenix Dactylifera L + doxorubicin (PDXG) groups were strictly fed PDL for two weeks. The control group (CG) and the doxorubicin group (DOXG) were fed a standard diet. During this time, 5 mg/kg of doxorubicin was injected intraperitoneally to DOXG and PDXG once a day.

Results: Administration of doxorubicin to the DOXG significantly increased tissue oxidative stress parameters and caused the cardiac biomarker troponin-I (TP-I) to be released into the circulation; on the contrary, the levels of potent antioxidants such as total glutathione, superoxide dismutase, and catalase significantly decreased in DOXG compared to the other three groups. However, feeding purely with PDL decreased oxidative stress parameters and TP-I levels in PDXG animals, despite exposure to doxorubicin. Additionally, an excessive decrease of tissue antioxidants was prevented when compared to the DOXG. Histopathological damage signs, such as necrosis and hemorrhage, were severe in the DOXG. However, in the PDXG animals, feeding with PDL provided the integrity of the heart tissue structure.

Conclusion: PDL was able to improve the cardiotoxic consequences of doxorubicin biochemically and histopathologically, possibly due to its antioxidant properties.

Keywords

Doxorubicin, oxidative stress, cardiotoxicity, Phoenix Dactylifera L, rat

References

• 1. Wojtacki J, Lewicka-Nowak E, Leśniewski-Kmak K. Anthracycline-induced cardiotoxicity: clinical course, risk factors, pathogenesis, detection and prevention--review of the literature. Medical science monitor: Med Sci Monit 2000;6(2):411-20.
• 2. Mancilla TR, Iskra B, Aune GJ. Doxorubicin-induced cardiomyopathy in children. Compr Physiol 2019;9(3):905-31. [Crossref]
• 3. Koutsoukis A, Ntalianis A, Repasos E, Kastritis E, Dimopoulos MA, Paraskevaidis I. Cardio-oncology: A Focus on Cardiotoxicity. Eur Cardiol 2018;13(1):64-9. [Crossref]
• 4. Rawat PS, Jaiswal A, Khurana A, Bhatti JS, Navik U. Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management. Biomed Pharmacother 2021;139:111708. [Crossref]
• 5. Klopčič I, Dolenc MS. Chemicals and drugs forming reactive quinone and quinone imine metabolites. Chem Res Toxicol 2019;32(1):1-34. [Crossref]
• 6. Abdel-Daim MM, Khalifa HA, Ahmed AA. Allicin ameliorates doxorubicin-induced cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis. Cancer Chemother Pharmacol 2017;80(4):745-53. [Crossref]
• 7. Abushouk AI, Ismail A, Salem AMA, Afifi AM, Abdel-Daim MM. Cardioprotective mechanisms of phytochemicals against doxorubicin-induced cardiotoxicity. Biomed Pharmacother 2017;90:935-46. [Crossref]
• 8. Song S, Chu L, Liang H, Chen J, Liang J, Huang Z, et al. Protective effects of dioscin against doxorubicin-induced hepatotoxicity via regulation of sirt1/FOXO1/NF-κb signal. Front Pharmacol 2019;10:1030. [Crossref]
• 9. Ayza MA, Zewdie KA, Tesfaye BA, Wondafrash DZ, Berhe AH. The role of antioxidants in ameliorating cyclophosphamide-induced cardiotoxicity. Oxid Med Cell Longev 2020;2020:4965171. [Crossref]
• 10. Attia AI, Reda FM, Patra AK, Elnesr SS, Attia YA, Alagawany M. Date (Phoenix dactylifera L.) by-products: Chemical composition, nutritive value and applications in poultry nutrition, an updating review. Animals (Basel) 2021;11(4):1133. [Crossref]
• 11. Siddiqi SA, Rahman S, Khan MM, Rafiq S, Inayat A, Khurram MS, et al. Potential of dates (Phoenix dactylifera L.) as natural antioxidant source and functional food for healthy diet. Sci Total Environ 2020;748:141234. [Crossref]
• 12. Vayalil PK. Antioxidant and antimutagenic properties of aqueous extract of date fruit (Phoenix dactylifera L. Arecaceae). J Agric Food Chem 2002;50(3):610-7. [Crossref]
• 13. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95(2):351-8. [Crossref]
• 14. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982;78(3):206-9. [Crossref]
• 15. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988;34(3):497-500. [Crossref]
• 16. Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121-6. [Crossref]
• 17. Shigenaga MK, Aboujaoude EN, Chen Q, Ames BN. Assays of oxidative DNA damage biomarkers 8-oxo-2’-deoxyguanosine and 8-oxoguanine in nuclear DNA and biological fluids by high-performance liquid chromatography with electrochemical detection. Methods Enzymol 1994;234:16-33. [Crossref]
• 18. Asami S, Hirano T, Yamaguchi R, Tomioka Y, Itoh H, Kasai H. Increase of a type of oxidative DNA damage, 8-hydroxyguanine, and its repair activity in human leukocytes by cigarette smoking. Cancer Res 1996;56(11):2546-9.
• 19. Bisht S, Dada R. Oxidative stress: Major executioner in disease pathology, role in sperm DNA damage and preventive strategies. Front Biosci (Schol Ed) 2017;9:420-47. [Crossref]
• 20. Habib HM, Ibrahim WH. Nutritional quality evaluation of eighteen date pit varieties. Int J Food Sci Nutr 2009;60 Suppl 1:99-111. [Crossref]
• 21. Daoud A, Mnafgui K, Turki M, Jmal S, Ayadi F, ElFeki A, et al. Cardiopreventive effect of ethanolic extract of date palm pollen against isoproterenol induced myocardial infarction in rats through the inhibition of the angiotensin-converting enzyme. Exp Toxicol Pathol 2017;69(8):656-65. [Crossref]
• 22. Cecerska-Heryć E, Surowska O, Heryć R, Serwin N, Napiontek-Balińska S, Dołęgowska B. Are antioxidant enzymes essential markers in the diagnosis and monitoring of cancer patients - A review. Clin Biochem 2021;93:1-8. [Crossref]
• 23. Liu X, Wang L, Cai J, Liu K, Liu M, Wang H, et al. N-acetylcysteine alleviates H2O2-induced damage via regulating the redox status of intracellular antioxidants in H9c2 cells. Int J Mol Med 2019;43(1):199-208. [Crossref]
• 24. Yoshioka Y, Negoro R, Kadoi H, Motegi T, Shibagaki F, Yamamuro A, et al. Noradrenaline protects neurons against H(2) O(2) -induced death by increasing the supply of glutathione from astrocytes via β(3) -adrenoceptor stimulation. J Neurosci Res 2021;99(2):621-37. [Crossref]
• 25. Al-Dashti YA, Holt RR, Keen CL, Hackman RM. Date palm fruit (Phoenix dactylifera): Effects on vascular health and future research directions. Int J Mol Sci 2021;22(9). [Crossref]
• 26. Wandt VK, Winkelbeiner N, Bornhorst J, Witt B, Raschke S, Simon L, et al. A matter of concern - Trace element dyshomeostasis and genomic stability in neurons. Redox Biol 2021;41:101877. [Crossref]
• 27. Baran A, Yildirim S, Ghosigharehaghaji A, Bolat İ, Sulukan E, Ceyhun SB. An approach to evaluating the potential teratogenic and neurotoxic mechanism of BHA based on apoptosis induced by oxidative stress in zebrafish embryo (Danio rerio). Hum Exp Toxicol 2021;40(3):425-38. [Crossref]
• 28. Diab KA, Aboul-Ela EI. In vivo comparative studies on antigenotoxicity of date palm (Phoenix Dactylifera L.) Pits Extract Against DNA damage induced by N-Nitroso-N-methylurea in Mice Toxicol Int 2012;19(3):279-86. [Crossref]
• 29. Pecoraro M, Pala B, Di Marcantonio MC, Muraro R, Marzocco S, Pinto A, et al. Doxorubicin induced oxidative and nitrosative stress: Mitochondrial connexin 43 is at the crossroads. Int J Mol Med 2020;46(3):1197-209. [Crossref]
• 30. He Q, Luo Y, Shi J, Tang X, Wei A. Pine (Pinus sylvestris L.) bark proanthocyanidins affords prevention of peroxynitrite-induced l-tyrosine nitration, DNA damage and hydroxyl radical formation. Pak J Pharm Sci 2020;33(1):141-8.
• 31. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol 2018;72(18):2231-64. [Crossref]