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Journals / The European Research Journal / 2026 / Volume: 5 Issue: 4

Cardioprotective effect of vitamin D and melatonin on doxorubicin-induced cardiotoxicity in rat model: an electrocardiographic, scintigraphic and biochemical study

Serdar Savaş Gül(Department of Nuclear Medicine, Gaziosmanpaşa University School of Medicine, Tokat, Turkey)0000-0003-4822-2588
Hatice Aygün(Department of Physiology, Gaziosmanpaşa University School of Medicine, Tokat, Turkey)0000-0002-4272-0562
Pages
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Publication Date
2019-07-04
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AI Summary & Key Takeaways

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⚡ TL;DR(Too Long; Didn't Read)

Conclusion: Vitamin D and melatonin treatment prevented all the parameters of DOX -induced cardiotoxicity in rats.

📌 3 Key Takeaways

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Objective & Hypothesis:Objectives: Doxorubicin ( DOX) is an antineoplastic drug that is widely used in chemotherapy but its cardiotoxicity is the most important side effect that limits the clinical use of this drug .
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Key Findings & Data:Methods: In this study, forty-nine adult male Wistar albino rats (220 ± 15 g) were randomly divided into seven groups (n = 7 each) , namely control (CON, n = 7), doxorubicin (DOX, n = 7), melatonin (MEL, n = 7), vitamin D (Vit D, n = 7), doxorubicin p lus melatonin (DOX+MEL, n = 7), doxorubicin plus vitamin D (DOX+Vit D, n = 7), and doxorubicin p lus melatonin and vitamin D (DOX+MEL+Vit D, n = 7) groups.
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Conclusion & Impact:Conclusion: Vitamin D and melatonin treatment prevented all the parameters of DOX -induced cardiotoxicity in rats.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:doxorubicin-induced cardiotoxicty · vitamin D · melatonin

Abstract

Objectives: Doxorubicin ( DOX) is an antineoplastic drug that is widely used in chemotherapy but its cardiotoxicity is the most important side effect that limits the clinical use of this drug . We investigated DOX treatment and the effects of vitamin D and melatonin on heart by electrocardiography, scintigraphic and biochemical methods. Methods: In this study, forty-nine adult male Wistar albino rats (220 ± 15 g) were randomly divided into seven groups (n = 7 each) , namely control (CON, n = 7), doxorubicin (DOX, n = 7), melatonin (MEL, n = 7), vitamin D (Vit D, n = 7), doxorubicin p lus melatonin (DOX+MEL, n = 7), doxorubicin plus vitamin D (DOX+Vit D, n = 7), and doxorubicin p lus melatonin and vitamin D (DOX+MEL+Vit D, n = 7) groups. Cardiotoxicity was induced by intraperitoneal injection (i.p.) of DOX (18 mg/kg, i.p.) on the 15 th , 16 th and 17 th days . Rats receiving vitamin D and melatonin treatment in the DOX-induced cardiotoxicity group received vitamin D (60,000 IU/kg, i.p.) were administered in a single dose and melatonin (40 mg/kg/day, i.p.) for 17 days and were injected with (18 mg/kg, i.p.) on doxorubicin 15 th , 16 th , and 17 th days. On the 18 th day electrocardiography (ECG), 99m Technetium pyrophosphate scintigraphy and biochemical parameters were assessed. Results: DOX caused changes in the ECG pattern, a significant decrease in heartbeat ( p < 0.01), P wave ( p < 0.001) and QRS complex durations ( p < 0.001), R wave amplitude ( p < 0.001); elevation in ST-segment ( p < 0.001) and decrease in QT interval ( p < 0,001), and R-R interval durations ( p < 0.001); increase in the serum levels of cardiac injury markers (CK, BUN, cardiac troponin T), ( p < 0.01) , and increased 99m Technetium pyrophosphate uptake ( p < 0.001) as compared to the CON group. MEL , Vit D and MEL+Vit D administration showed a same protective effect against DOX-induced altered ECG pattern. Pre-treatment with MEL , Vit D and MEL+Vit D significantly protected the heart from the toxic effect of DOX, by decreasing the levels of of cardiac injury markers (CK, BUN, cardiac troponin T) ( p < 0.001) and decreased the elevated level of 99m Technetium pyrophosphate uptake ( p < 0.001). Conclusion: Vitamin D and melatonin treatment prevented all the parameters of DOX -induced cardiotoxicity in rats.

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Cite This Article

Gül, S. S., Aygün, H. (2019). Cardioprotective effect of vitamin D and melatonin on doxorubicin-induced cardiotoxicity in rat model: an electrocardiographic, scintigraphic and biochemical study. The European Research Journal, Volume: 5 Issue: 4. https://doi.org/10.18621/eurj.410029

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References (38)

  1. Lefrak EA, Pitha J, Rosenheim S, Gottlieb JA. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 1973;32:302-14.
  2. Bilginoğlu A, Aydın D, Ozsoy S, Aygün H. Protective effect of melatonin on adriamycin-induced cardiotoxicity in rats. Turk Kardiyol Dern Ars 2014;42:265-73.
  3. Swamy AH, Wangikar U, Koti BC, Thippeswamy AH, Ronad PM, Manjula DV. Cardioprotective effect of ascorbic acid on doxorubicin-induced myocardial toxicity in rats. Indian J Pharmacol 2011;43:507-11.
  4. Anjos Ferreira AL, Russell RM, Rocha N, Placido Ladeira MS, Favero Salvadori DM, Oliveira Nascimento MC, et al. Effect of lycopene on doxorubicin-induced cardiotoxicity: an echocardiographic, histological and morphometrical assessment. Basic Clin Pharmacol Toxicol 2007;101:16-24.
  5. Xin Y, Zhang S, Gu L, Liu S, Gao H, You Z, et al. Electrocardiographic and biochemical evidence for the cardioprotective effect of antioxidants in acute doxorubicin-induced cardiotoxicity in the beagle dogs. Biol Pharm Bull 2011;34:1523-6.
  6. Othman AI, El-Missiry MA, Amer MA, Arafa M. Melatonin controls oxidative stress and modulates iron, ferritin, and transferrin levels in adriamycin treated rats. Life Sci 2008;83:563-8.
  7. Ahmed HH, Mannaa F, Elmegeed GA, Doss SH. Cardioprotective activity of melatonin and its novel synthesized derivates on doxorubicin-induced cardiotoxicity. Bioorg Med Chem 2005;13:1847-57.
  8. Prufer K, Veenstra TD, Jirikowski GF, Kumar R. Distribution of 1,25- dihydroxyvitamin D3 receptor immunoreactivity in the rat brain and spinal cord. J Chem Immunol 1999;16:135-45.
  9. Langub MC, Herman JP, Malluche HH, Koszewski NJ. Evidence of functional vitamin D receptors in rat hippocampus. Neuroscience 2001;104:49-56.
  10. Walbert T, Jirikowski GF, Prufer K. Distribution of 1,25-dihydroxyvitamin D3 receptor immunoreactivity in the limbic system. Horm Metab Res 2001;33:525-31.
  11. Kunadian V, Ford GA, Bawamia B, Qiu W, Manson JE. Vitamin D deficiency and coronary artery disease: a review of the evidence. Am Heart J 2014;167:283-91.
  12. Majumdar V, Prabhakar P, Kulkarni GB, Christopher R. Vitamin D status, hypertension and ischemic stroke: a clinical perspective. J Hum Hypertens 2015;29: 669-74.
  13. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J Clin Endocrinol Metab 2012;97:1153-8.
  14. Bansal N, Zelnick L, Robinson-Cohen C, Hoofnagle AN, Ix JH, Lima JA, et al. Serum parathyroid hormone and 25-hydroxyvitamin D concentrations and risk of incident heart failure: the Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc 2014;3:e001278.
  15. Park CW, Oh YS, Shin YS, Kim CM, Kim YS, Kim SY, et al. Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis patients with secondary hyperparathyroidism. Am J Kidney Dis 1999;33:73-81.
  16. Shoji T, Shinohara K, Kimoto E, Emoto M, Tahara H, Koyama H, et al. Lower risk forcardiovascular mortality in oral 1-alpha-hydroxy vitamin D3 users in a haemodialysis population. Nephrol Dial Transplant 2004;19:179-84.
  17. Nemerovski CW, Dorsch MP, Simpson RU, Bone HG, Aaronson KD, Bleske BE. Vitamin D and cardiovascular disease. Pharmacotherapy 2009;29:691-708.
  18. Suzuki J, Yanagisawa A, Shigeyama T, Tsubota J, Yasumura T, Shimoyama K, et al. Early detection of anthracycline-induced cardiotoxicity by radionuclide angiocardiography. Angiology1999;50:37-45.
  19. Kelishomi RB, Ejtemaeemehr S, Tavangar SM, Rahimian R, Mobarakeh JI, Dehpour AR. Morphine is protective against doxorubicin-induced cardiotoxicity in rat. Toxicology 2008;243;96-104.
  20. Koti BC, Nagathan S, Vishwanathswamy A, Gadad PC, Thippeswamy A. Cardioprotective effect of Vedic Guard against doxorubicin-induced cardiotoxicity in rats: A biochemical, electrocardiographic, and histopathological study. Pharmacogn Mag 2013;9:176-81.
  21. Bhatt L, Joshi V. Mangifera indica L. leaf extract alleviates doxorubicin induced cardiac stress. J Intercult Ethnopharmacol 2017;6:284-9.
  22. Rossi F, Filippelli W, Russo S, Filippelli A, Berrino L. Cardiotoxicity of doxorubicin: Effects of drugs inhibiting the release of vasoactive substances. Pharmacol Toxicol 1994;75:99-107.
  23. Holland RP, Brooks H. TQ-ST segment mapping: Critical review and analysis of current concepts. Am J Cardiol 1977;40:110-29.
  24. Villani F, Monti E, Piccinini F, Favalli L, Lanza E, Rozza Dionigi A, et al. Relationship between doxorubicin-induced ECG changes and myocardial alterations in rats. Tumori 1986;72:323-9.
  25. Fujita T. Formation and removal of reactive oxygen species, lipid peroxides and free radicals, and their biological effects. Yakugaku Zasshi 2002;122:203-18.
  26. Zhang YW, Shi J, Li YJ, Wei L. Cardiomyocyte death in doxorubicin-induced cardiotoxicity. Arch Immunol Ther Exp (Warsz) 2009;57:435-45.
  27. Christenson ES, James T, Agrawal V, Park BH. Use of biomarkers for the assessment of chemotherapy-induced cardiac toxicity. Clin Biochem 2015;48:223-35.
  28. Ozdoğan K, Taşkın E, Dursun N. Protective effect of carnosine on adriamycin-induced oxidative heart damage in rats. Anadolu Kardiyol Derg 2011;11:3-10.
  29. Momin F, Shikalgar T, Naikwade N, Kalai B. Cardioprotective effect of methanolic extract of Ixora coccinea Linn. leaves on doxorubicin-induced cardiac toxicity in rats. Indian J Pharmacol 2012;44:178-83.
  30. Okuda K, Nohara R, Fujita M, Tamaki N, Konishi J, Sasayama S. Technetium-99m-pyrophosphate uptake as an indicator of myocardial injury without infarct. J Nucl Med 1994;35:1366-70.
  31. Okuda K, Nohara R, Ogino M, Tamaki N, Konishi J, Fujita M, et al. Limitation of infarct size with preconditioning and calcium antagonist (diltiazem): difference in 99mTc-PYP uptake in the myocardium. Ann Nucl Med 1996;10:201-9.
  32. Kawano M, Taki J, Kinuya S, Higuchi T, Nakajima K, Miyazaki Y, et al. Improvement of 99mTc-pyrophosphate scintigraphy in detection of acute myocardial infarction: combined with 99mTc-tetrofosmin. Kaku Igaku 2001;38:707-13.
  33. Mochizuki T, Murase K, Higashino H, Miyagawa M, Sugawara Y, Kikuchi T, et al. Ischemic "memory image" in acute myocardial infarction of 123I-BMIPP after reperfusion therapy: a comparison with 99mTc-pyrophosphate and 201Tl dual-isotope SPECT. Ann Nucl Med 2002;16:563-8.
  34. Affleck DG, Edelman L, Morris SE, Saffle JR. Assessment of tissue viability in complex extremity injuries: utility of the pyrophosphate nuclear scan. J Trauma 2001;50:263-9.
  35. Chang HR, Kao CH, Lian JD, Shu KH, Cheng CH, Wu MJ, et al. Evaluation of the severity of traumatic rhabdomyolysis using technetium-99m pyrophosphate scintigraphy. Am J Nephrol 2001;21:208-14.
  36. Matthews KL, Aarsvold JN, Mintzer RA, Chen CT, Lee RC. Tc-99m pyrophosphate imaging of poloxamer-treated electroporated skeletal muscle in an in vivo rat model. Burns 2006;32:755-64.
  37. Walker UA, Garve K, Brink I, Miehle N, Peter HH, Kelly T. 99mTechnetium pyrophosphate scintigraphy in the detection of skeletal muscle disease. Clin Rheumatol 2007;26:1119-22.
  38. Çiftçi ÖD, Gül SS, Açıksarı K, Maman A, Çavuşoğlu T, Bademci R, et al. The diagnostic utility of scintigraphy in esophageal burn: a rat model. J Surg Res 2016;200:495-500.