Anatomopathological study of cardiomyopathy induced by doxorubicin in rats

Abstract

Purpose:The development of an experimental model of myocardiopathy induced by Doxorubicin in rats. Methods: 16 wistar male rats were randomized in two groups: Group I (placebo) and Group II (Doxorubicin -5mg/kg). After six months, the animals were subjected to cardiotomy and their hearts were weighted and submitted to transversal cuts, from which fragments for a macro and micro study were obtained. These fragments were studied considering their external and internal diameters and the thickness of the left ventricle (LV). The histological pieces were analyzed for the presence of fibrosis, cytoplasmic vacuolization, necrosis and size of nucleus variation. Data obtained was submitted to statistical analysis with Student's t test. Results: The hearts of the animals in Group II increased 41% in relation to their weight; 33% in the internal diameter and 14% in the external diameter of the LV cavity; and 24% in the thickness of the wall. Fibrosis of the myocardial tissue was observed in 75% of the animals of Group II; all the animals presented miocyte cytoplasmatic vacuolization; myocardial necrosis was present in 75% of the animals; and 87/% presented variation in the size of myocite nuclei. The presence of polymorphonuclear cells was also observed. Conclusion: Doxorubicin was effective in the promotion of macro and microscopic alterations in the cardiac tissue of rats, possibly constituting a model for the experimental study of myocardiopathy. Key words: Cardiomyopathies. Doxorubicin. Rats. RESUMOObjetivo: Desenvolver um modelo experimental de miocardiopatia induzida por doxorrubicina em ratos. Métodos: 16 ratos Wistar machos foram randomizados em 2 grupos: Grupo I (placebo) e Grupo II (doxorrubicina 5mg/kg). Após 6 meses, os animais foram submetidos a cardiotomia e seus corações foram pesados e submetidos a cortes transversais. Estes fragmentos foram estudados considerando seus diâmetros externos e internos e a espessura do ventrículo esquerdo. As peças histológicas foram analisadas quanto à presença de fibrose, vacuolização citoplasmática, necrose e variação do tamanho do núcleo. Os resultados foram submetidos a análise estatística pelo teste t de Student. Resultados: Os corações dos animais do grupo II aumentaram 41% em relação ao peso; 33% no diâmetro interno e 14% no diâmetro externo; e 24% na espessura da parede do VE. Fibrose do tecido miocárdico foi observada em 75% dos animais do grupo II; todos os animais apresentaram vacuolização citoplasmática dos miócitos; Houve necrose miocárdica em 75% dos animais e 87% apresentaram variação no tamanho do núcleo. A presença de células polimorfonucleares também foi observada. Conclusão: A doxorrubicina foi efetiva na promoção de alterações macro e microscópicas no tecido cardíaco de ratos, possivelmente constituindo-se num modelo experimental para estudo da miocardiopatia. Descritores: Cardiomiopatias. Doxorrubicina. Ratos.

Folic acid ameliorates celecoxib cardiotoxicity in a doxorubicin heart failure rat model

“…The repeated administrations of DOX at this dose level produces delayed, progressive, and chronic cardiotoxicity with myocardial lesions that are similar to those reported in humans (Pontes et al. 2010 ). DOX-induced cardiomyopathy was manifested by significant increases in the serum LDH, CK-MB, Tn-T and TNF-α levels as markers of cardiac damage.…”

Cardioprotective effects of curcumin and carvacrol in doxorubicin‐treated rats: Stereological study

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The most frequent etiologies of heart failure include ischemic heart disease, hypertension, diabetes, and toxins (e.g., alcohol and cytotoxic drugs) (Kemp & Conte, 2012;Pontes et al, 2010). Along with these toxic agents, doxorubicin (DOX) was considered in the present study.

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Upregulation of IGF‐IIRα intensifies doxorubicin‐induced cardiac damage

“…Notably, DOX treatment intensified the cardiac structural damage in transgenic animals IGF-IIRα and caused more severe cardiac tissue damage. DOX treatment has been implicated to cause cardiotoxicity 17 ; however, IGF-IIRα showed an additive role in the cardiac damaging effects triggered by DOX that severely impaired the heart function. To further ascertain the role of IGF-IIRα in DOX-induced cardiac damage, we determined the protein expression of survival markers upon IGF-IIRα overexpression and/or DOX treatment in both in vitro and in vivo systems.…”