Effects of omega 3 on doxorubicin-induced cardiotoxicity in an experimental rabbit model





Omega 3; Cardiotoxicity; Doxorubicin.


To evaluate the effects of the use of omega 3 at different doses, following the response through stereological and morphometric evaluations in doxorubicin-induced acute cardiotoxicity in an experimental rabbit model. Thirty healthy adult New Zealand rabbits were divided into six groups with different doses of omega 3 treatment, GT125, GT500 and GT 2000, receiving doses of 125mg / kg, 500mg / kg and 2000mg / kg, respectively. The induction of acute cardiotoxicity with doxorubicin was treated for six days prior to intravenous administration of 10mg / kg single dose. Then, the animals were euthanized and myocardial samples were collected for stereological and morphometric evaluations. The stereological evaluation showed an increase in the transverse area of ​​cardiomocytes between the SHAM and GT2000 groups and an increase in the interstitial collagen volume density between the SHAM and GT500 and SHAM and GT2000 groups. The omega 3 500mg/kg dose has the potential to attenuate the fibrotic effects of doxorubicin use and the use of a single dose of 10mg/kg doxorubicin can be used as an acute dilated cardiomyopathy induction protocol in an experimental model using rabbits.


Chen, Y., Liu, W., Li, W., & Gao, C. (2010). Autologous bone marrow mesenchymal cell transplantation improves left ventricular function in a rabbit model of dilated cardiomyopathy. Experimental and molecular pathology, 88(2), 311-315.

Curry, H. L., Parkes, S. E., Powell, J. E., & Mann, J. R. (2006). Caring for survivors of childhood cancers: the size of the problem. European Journal of Cancer, 42(4), 501-508.

El-Sayyad, H. I., Ismail, M. F., Shalaby, F. M., Abou-El-Magd, R. F., Gaur, R. L., Fernando, A., & Ouhtit, A. (2009). Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats. International journal of biological sciences, 5(5), 466.

Farraj, A. K., Hazari, M. S., & Cascio, W. E. (2011). The utility of the small rodent electrocardiogram in toxicology. Toxicological sciences, 121(1), 11-30.

Gava, F. N., Zacché, E., Ortiz, E. M., Champion, T., Bandarra, M. B., Vasconcelos, R. O. & Camacho, A. A. (2013). Doxorubicin induced dilated cardiomyopathy in a rabbit model: an update. Research in Veterinary Science, 94(1), 115-121.

Gewirtz, D. (1999). A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochemical pharmacology, 57(7), 727-741.

Hardman, W. E. (2004). (n-3) fatty acids and cancer therapy. The Journal of nutrition, 134(12), 3427S-3430S.

Heydari, B., Abdullah, S., Pottala, J. V., Shah, R., Abbasi, S., Mandry, D., ... & Appelbaum, E. (2016). Effect of omega-3 acid ethyl esters on left ventricular remodeling after acute myocardial infarction: the OMEGA-REMODEL randomized clinical trial. Circulation, 134(5), 378-391.

Kero, A. E., Järvelä, L. S., Arola, M., Malila, N., Madanat‐Harjuoja, L. M., Matomäki, J., & Lähteenmäki, P. M. (2014). Cardiovascular morbidity in long‐term survivors of early‐onset cancer: a population‐based study. International journal of cancer, 134(3), 664-673.

Klinnikova, M. G., Lushnikova, E. L., Koldysheva, E. V., Tolstikova, T. G., Sorokina, I. V., Yuzhik, E. I., & Mzhelskaya, M. M. (2016). Cardiotoxic and Dyslipidemic Effects of Doxorubicin and Betulinic Acid Amide. Bulletin of experimental biology and medicine, 162(2), 277-282.

Leaf, A., Kang, J. X., Xiao, Y. F., & Billman, G. E. (2003). Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Circulation, 107(21), 2646-2652.

Luu, A. Z., Chowdhury, B., Al-Omran, M., Teoh, H., Hess, D. A., & Verma, S. (2018). Role of endothelium in doxorubicin-induced cardiomyopathy. JACC: Basic to Translational Science, 3(6), 861-870.

Moreno, C., Macías, Á., Prieto, Á., De La Cruz, A., González, T., & Valenzuela, C. (2012). Effects of n− 3 polyunsaturated fatty acids on cardiac ion channels. Frontiers in physiology, 3, 245.

Murphy, R. A., Mourtzakis, M., Chu, Q. S., Baracos, V. E., Reiman, T., & Mazurak, V. C. (2011). Supplementation with fish oil increases first‐line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer, 117(16), 3774-3780.

Oeffinger, K. C., Mertens, A. C., Sklar, C. A., Kawashima, T., Hudson, M. M., Meadows, A. T. & Schwartz, C. L. (2006). Chronic health conditions in adult survivors of childhood cancer. New England Journal of Medicine, 355(15), 1572-1582.

Olson, H. M., & Capen, C. C. (1978). Chronic cardiotoxicity of doxorubicin (adriamycin) in the rat: morphologic and biochemical investigations. Toxicology and applied pharmacology, 44(3), 605-616.

Oshima, T., & Fujiu, K. (2018). The Impact of Non-Cardiac Drugs on the Cardiac Repolarization Phase. International heart journal, 59(4), 677-679.

Pereira, L. M., Vianna, G. M., & Mandarim-de-Lacerda, C. A. (1998). Morphology and stereology of the myocardium in hypertensive rats. Correlation with the time of nitric oxide synthesis inhibition. Arquivos brasileiros de cardiologia, 70(6), 397-402.

Pereira Neto, G. B., Andrade, J. N. B., Sousa, M. G., & Camacho, A. A. (2006). Holter electrocardiography in dogs showing doxorubicin-induced dilated cardiomyopathy. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, 58(6), 1037-1042.

Pogwizd, S. M., & Bers, D. M. (2008). Rabbit models of heart disease. Drug Discovery Today: Disease Models, 5(3), 185-193.

Polegato, B. F., Minicucci, M. F., Azevedo, P. S., Carvalho, R. F., Chiuso-Minicucci, F., Pereira, E. J., ... & Matsubara, L. S. (2015). Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats. Cellular Physiology and Biochemistry, 35(5), 1924-1933.

Preto, E., Lima, N. E., Simardi, L., Fonseca, F. L. A., Fragata Filho, A. A., & Maifrino, L. B. M. (2015). Effect of mild aerobic training on the myocardium of mice with chronic Chagas disease. Biologics: targets & therapy, 9, 87.

Rafati, A., Jafarinezhad, Z., Karbalay-Doust, S., Hosseini, L., & Noorafshan, A. (2017). Microscopic evaluation of the ventricular tissue using stereological and Voronoi tessellation methods: Application on doxorubicin-induced cardiotoxicity in rats. Micron, 101, 1-7.

Saravanan, P., West, A. L., Bridgewater, B., Davidson, N. C., Calder, P. C., Dobrzynsky, H., ... & O'Neill, S. C. (2016). Omega-3 fatty acids do not alter P-wave parameters in electrocardiogram or expression of atrial connexins in patients undergoing coronary artery bypass surgery. Ep Europace, 18(10), 1521-1527.

Szabuniewicz, M., Hightower, D., & Kyzar, J. R. (1971). The electrocardiogram, vectorcardiogram and spatiocardiogram in the rabbit. Canadian Journal of Comparative Medicine, 35(2), 107.

Talavera, J., Giraldo, A., Fernández-Del-Palacio, M. J., García-Nicolás, O., Seva, J., Brooks, G., & Moraleda, J. M. (2015). An upgrade on the rabbit model of anthracycline-induced cardiomyopathy: shorter protocol, reduced mortality, and higher incidence of overt dilated cardiomyopathy. BioMed research international, 2015.

Tilley, L. T. (1992). Essentials of canine and feline electrocardiography. 3. ed. Philadelphia: Lea & Febiger;

Travers, J. G., Kamal, F. A., Robbins, J., Yutzey, K. E., & Blaxall, B. C. (2016). Cardiac fibrosis: the fibroblast awakens. Circulation research, 118(6), 1021-1040.

Viskin, S., Justo, D., Halkin, A., & Zeltser, D. (2003). Long QT syndrome caused by noncardiac drugs. Progress in cardiovascular diseases, 45(5), 415-427.

Voskoboinik, A., Prabhu, S., Sugumar, H., & Kistler, P. M. (2018). Effect of dietary factors on cardiac rhythm. The American journal of cardiology, 122(7), 1265-1271.

Xue, H., Ren, W., Denkinger, M., Schlotzer, E., & Wischmeyer, P. E. (2016). Nutrition Modulation of Cardiotoxicity and Anticancer Efficacy Related to Doxorubicin Chemotherapy by Glutamine and ω‐3 Polyunsaturated Fatty Acids. Journal of Parenteral and Enteral Nutrition, 40(1), 52-66.




How to Cite

BARROS , J. C. de; PEREIRA, A. G.; RODRIGUES , M. A.; PAULINO JUNIOR, D. . Effects of omega 3 on doxorubicin-induced cardiotoxicity in an experimental rabbit model . Research, Society and Development, [S. l.], v. 10, n. 13, p. e60101320993, 2021. DOI: 10.33448/rsd-v10i13.20993. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/20993. Acesso em: 8 dec. 2021.



Agrarian and Biological Sciences