IIARD International Institute of Academic Research and Development

INTERNATIONAL JOURNAL OF HEALTH AND PHARMACEUTICAL RESEARCH (IJHPR )

E-ISSN 2545-5737
P-ISSN 2695-2165
VOL. 9 NO. 4 2024
DOI: 10.56201/ijhpr.v9.no4.2024.pg37.46

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Cardiac Dysfunction and Mitochondrial Impairment in A Rat Model of Doxorubicin-Induced Cardiotoxicity

Araa Mahdi Hussein AI-Rubaye

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Abstract

Doxorubicin (DOX) is an effective chemotherapeutic agent widely used to treat various cancers. However, its clinical use is significantly limited due to its dose-dependent cardiotoxic effects, which lead to cardiac dysfunction and mitochondrial impairment. This study investigates the relationship between DOX-induced cardiotoxicity and mitochondrial dysfunction in a rat model. Key cardiac function parameters and mitochondrial oxidative stress markers were assessed to determine the impact of DOX treatment. The results reveal significant deterioration in cardiac function and mitochondrial integrity, suggesting that mitochondrial damage is central to DOX-induced cardiotoxicity.

keywords:

DOX, Rat, Cardiotoxicity

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References:

1. Singal, P. K., & Iliskovic, N. (1998). Doxorubicin-induced cardiomyopathy. New
England Journal of Medicine, 339(13), 900-905.
2. Pacher, P., & Szabo, C. (2005). Role of peroxynitrite in the pathogenesis of
cardiovascular disease. Cardiovascular Research, 68(1), 121-137.
3. Weiss, R. B. (1992). The anthracyclines: Will we ever find a better doxorubicin?
Seminars in Oncology, 19(6), 670-686.
4. Minotti, G., Menna, P., Salvatorelli, E., Cairo, G., & Gianni, L. (2004). Anthracyclines:
Molecular advances and pharmacologic developments in antitumor activity and
cardiotoxicity. Pharmacological Reviews, 56(2), 185-229.
5. Wallace, K. B. (2003). Doxorubicin-induced cardiac mitochondrionopathy.
Pharmacology & Therapeutics, 97(3), 227-244.
6. Monteiro, P., & Gonçalves, L. (2021). Cardiotoxicity of doxorubicin: From
mitochondrial damage to cell death. Frontiers in Cardiovascular Medicine, 8,
631453.
7. Chatterjee, K., Zhang, J., Honbo, N., & Karliner, J. S. (2010). Doxorubicin
cardiomyopathy. Cardiology, 115(2), 155-162.
8. Fabbri, E., & Angeletti, S. (2018). Oxidative stress and mitochondrial dysfunction in
doxorubicin cardiotoxicity. Antioxidants & Redox Signaling, 19(3), 165-178.
9. Doroshow, J. H. (1983). Effect of anthracycline antibiotics on oxygen radical formation
in rat heart. Cancer Research, 43(2), 460-472.
10. Murphy, M. P. (2009). How mitochondria produce reactive oxygen species.
Biochemical Journal, 417(1), 1-13.
11. Neilan, T. G., & Jassal, D. S. (2015). Anthracycline cardiotoxicity: Basic and clinical
perspectives. Heart, 101(11), 908-918.
12. Olson, R. D., & Mushlin, P. S. (1990). Doxorubicin cardiotoxicity: Analysis of
prevailing hypotheses. The FASEB Journal, 4(13), 3076-3086.
13. Green, D. R., & Reed, J. C. (1998). Mitochondria and apoptosis. Science, 281(5381),
1309-1312.
14. Abraham, B. P., & Lyseng-Williamson, K. A. (2007). Dexrazoxane: A review of its use
for cardioprotection during anthracycline chemotherapy. Drugs, 67(13), 2043-2071.
15. Jones, R. L., & Swanton, C. (2012). Anthracyclines: Cardiovascular toxicity in cancer
survivors. Clinical Oncology, 24(5), 311-322.
16. Octavia, Y., Tocchetti, C. G., & Gabrielson, K. L. (2012). Doxorubicin-induced
cardiomyopathy: From molecular mechanisms to therapeutic strategies. Journal of
Molecular and Cellular Cardiology, 52(6), 1213-1225.17. Lenaz, G., & Genova, M. L. (2007). Structural and functional organization of the
mitochondrial respiratory chain: A dynamic super-assembly. International Journal of
Biochemistry & Cell Biology, 39(11), 1990-1999.
18. Keizer, H. G., & Pinedo, H. M. (1990). Doxorubicin (adriamycin) pharmacokinetics
and metabolism. Cancer Treatment Reviews, 17(3), 233-243.
19. Zhang, S., Liu, X., & Bawa-Khalfe, T. (2012). Identification of the molecular
mechanisms underlying doxorubicin-induced cardiotoxicity. Journal of Clinical
Investigation, 122(7), 2814-2823.
20. Ayoub, S. S., Baxter, G. F., & Davidson, S. M. (2019). The role of mitochondria in
doxorubicin-induced cardiotoxicity. Journal of Molecular and Cellular Cardiology,
129, 126-135.
21. Cadenas, E., & Davies, K. J. A. (2000). Mitochondrial free radical generation, oxidative
stress, and aging. Free Radical Biology and Medicine, 29(3-4), 222-230.
22. Deng, S., & Yan, T. (2007). Mitochondrial dysfunction in doxorubicin-induced
cardiomyopathy. Cell Research, 17(11), 940-941.
23. Conklin, K. A. (2004). Coenzyme Q10 for prevention of anthracycline-induced
cardiotoxicity. Integrative Cancer Therapies, 4(2), 110-130.
24. Wu, X., & Brewer, G. J. (2012). Redox imbalance and mitochondrial damage in the
doxorubicin-induced cardiotoxicity model. PLoS ONE, 7(6), e41103.
25. Danz, E. D., Skramsted, J., Henry, N., Bennett, J. A., & Keller, R. S. (2009). Resveratrol
prevents doxorubicin cardiotoxicity through mitochondrial stabilization and the SIRT1
pathway. Free Radical Biology and Medicine, 46(12), 1589-1597.
26. Kang, Y. J. (2010). Antioxidant defenses and cardiac remodeling in doxorubicininduced cardiotoxicity. Cardiovascular Toxicology, 10(3), 165-176.
27. Ferreira, A. L., & Matsubara, L. S. (1997). Anthracycline-induced cardiotoxicity.
Cardiovascular Research, 33(2), 372-383.
28. Hengstler, J. G., Fuchs, J., & Oesch, F. (1999). DNA strand breaks induced by
doxorubicin via intercalation and iron-mediated free radical formation. Cancer
Research, 59(2), 364-369.
29. Berthiaume, J. M., & Wallace, K. B. (2007). Persistent alterations to the gene
expression profile of the heart following chronic doxorubicin treatment.
Cardiovascular Toxicology, 7(3), 179-188.
30. Dobson, G. P., & Jones, M. W. (2004). Oxidative stress in heart failure and the role of
antioxidants. Progress in Cardiovascular Diseases, 46(4), 288-305.
31. Murphy, M. P. (2009). How mitochondria produce reactive oxygen species.
Biochemical Journal, 417(1), 1-13.
32. Arola, O. J., Saraste, A., Pulkki, K., Kallajoki, M., Parvinen, M., & Voipio-Pulkki, L.
M. (2000). Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis.
Cancer Research, 60(7), 1789-1792.
33. Ewer, M. S., & Ewer, S. M. (2010). Cardiotoxicity of anticancer treatments. Nature
Reviews Cardiology, 7(10), 564-575.
34. Sawyer, D. B., Peng, X., Chen, B., & Pentassuglia, L. (2010). Mechanisms of
anthracycline cardiac injury: Can we identify strategies for cardioprotection? Progress
in Cardiovascular Diseases, 53(2), 105-113.
35. Myers, C., & Bonow, R. (1992). Is anthracycline cardiotoxicity clinically relevant?
Journal of Clinical Oncology, 10(8), 1746-1752.36. Swain, S. M., Whaley, F. S., & Ewer, M. S. (2003). Congestive heart failure in patients
treated with doxorubicin. Cancer, 97(11), 2869-2879.
37. Carvalho, F. S., Burgeiro, A., Garcia, R., Moreno, A. J., Carvalho, R. A., & Oliveira,
P. J. (2014). Doxorubicin-induced cardiotoxicity: From bioenergetic failure and cell
death to cardiomyopathy. Medicinal Research Reviews, 34(1), 106-135.

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