Efeitos do ômega 3 na cardiotoxicidade induzida por doxorrubicina em modelo experimental com coelhos

Autores

DOI:

https://doi.org/10.33448/rsd-v10i13.20993

Palavras-chave:

Ômega 3; Cardiotoxicidade; Doxorrubicina.

Resumo

Avaliar os efeitos do uso do ômega 3 em diferentes doses, acompanhando a resposta através de avaliações estereológicas e morfométricas na cardiotoxicidade aguda induzida por doxorrubicina em modelo experimental com coelhos. Trinta coelhos adultos hígidos da raça nova Zelândia foram distribuídos em seis grupos com diferentes doses de tratamento com ômega 3 sendo GT125, GT500 e GT 2000, recebendo as doses de 125mg/kg, 500mg/kg e 2000mg/kg, respectivamente. Foram tratados durante seis dias prévios a indução da cardiotoxicidade aguda com doxorrubicina, utilizando a dose de 10mg/kg intravenosa em aplicação única. Ato contínuo, os animais foram eutanasiados e amostras do miocárdio foram coletadas para avaliações estereológicas e morfométricas. A avaliação estereológica evidenciou aumento na área transversa de cardiomócitos entre os grupos SHAM e GT2000 e aumento na densidade de volume de colágeno intersticial ente os grupos SHAM e GT500 e SHAM e GT2000. A dose de 500mg/kg de ômega 3 apresentou potencial para atenuar os efeitos fibróticos do uso da doxorrubicina e a utilização da dose de 10mg/kg de doxorrubicina em dose única pode ser utilizada como protocolo de indução de cardiomiopatia dilatada aguda em modelo experimental utilizando coelhos.

Referências

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.

Downloads

Publicado

04/10/2021

Como Citar

BARROS , J. C. de; PEREIRA, A. G.; RODRIGUES , M. A.; PAULINO JUNIOR, D. . Efeitos do ômega 3 na cardiotoxicidade induzida por doxorrubicina em modelo experimental com coelhos. 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: 5 jul. 2024.

Edição

Seção

Ciências Agrárias e Biológicas