Effect of Lycopene on Doxorubicin‐Induced Cardiotoxicity: An Echocardiographic, Histological and Morphometrical Assessment

Abstract

Doxorubicin is an excellent chemotherapeutic agent utilized for several types of cancer but the irreversible doxorubicin-induced cardiac damage is the major limitation for its use. Oxidative stress seems to be associated with some phase of the toxicity mechanism process. To determine if lycopene protects against doxorubicin-induced cardiotoxicity, male Wistar rats were randomly assigned either to control, lycopene, doxorubicin or doxorubicin + lycopene groups. They received corn oil (control, doxorubicin) or lycopene (5 mg /kg body weight a day) (lycopene, doxorubicin + lycopene) by gavage for a 7-week period. They also received saline (control, lycopene) or doxorubicin (4 mg/kg) (doxorubicin, doxorubin + lycopene) intraperitoneally by week 3, 4, 5 and 6. Animals underwent echocardiogram and were killed for tissue analyses by week 7. Mean lycopene levels (nmol/kg) in liver were higher in the doxorubicin + lycopene group (5822.59) than in the lycopene group (2496.73), but no differences in lycopene were found in heart or plasma of these two groups. Lycopene did not prevent left ventricular systolic dysfunction induced by doxorubicin. However, morphologic examination revealed that doxorubicin-induced myocyte damage was significantly suppressed in rats treated with lycopene. Doxorubicin treatment was followed by increase of myocardium interstitial collagen volume fraction. Our results show that: (i) doxorubicin-induced cardiotoxicity was confirmed by echocardiogram and morphological evaluations; (ii) lycopene absorption was confirmed by its levels in heart, liver and plasma; (iii) lycopene supplementation provided myocyte protection without preventing interstitial collagen accumulation increase; (iv) doxorubicin-induced cardiac dysfunction was not prevented by lycopene supplementation; and (v) lycopene depletion was not observed in plasma and tissues from animals treated with doxorubicin.

Electrocardiographic and Biochemical Evidence for the Cardioprotective Effect of Antioxidants in Acute Doxorubicin-Induced Cardiotoxicity in the Beagle Dogs

“…[3][4][5] However, most of them were tried with limited success in preventing DOX-associated cardiotoxicity in large-sized animals such as dogs or pigs.…”

“…1) A number of antioxidants, such as lycopene, N-acetylcysteine and vitamin E were proved to ameliorate the DOXinduced cardiac cell damage without compromising its antitumor efficacy in the rats or mice model. [3][4][5] However, most of them were tried with limited success in preventing DOX-associated cardiotoxicity in large-sized animals such as dogs or pigs. 6) Lycium barbarum, a famous Chinese medicinal herb, has a long history of use as an antioxidant and to promote sexual fertility.…”

Ação do extrato etanólico da casca do pequi (Caryocar brasiliense) na cardiotoxicidade crônica induzida por doxorrubicina em ratos

“…Já o grupo que foi submetido à eutanásia quatro dias após a aplicação apresentou taxa de mortalidade de 29%. Índices ainda maiores, acima de 50% de mortalidade, foram descritos por Ferreira et al (2007) ao acumular 16mg/kg de DOX. Neste estudo, a ausência de mortalidade relacionada ao fármaco se deve, possivelmente, à menor dose de DOX utilizada e ao intervalo de tempo decorrido entre os tratamentos e a necropsia.…”

Extrato hidroalcoolico da casca do pequi (Caryocar brasiliense) em ratos submetidos à aplicação de doxorrubicina

“…Pesquisas relatam a redução da cardiotoxicidade da DOX com o uso de substâncias antioxidantes (FERREIRA et al, 2007;GRANADOS-PRINCIPAL et al, 2010) e comprovam que dietas ricas em antioxidantes naturais contribuem para a redução significativa de doenças crônicas e degenerativas (PAULA JÚNIOR et al, 2006;ROESLER et al, 2007;LIMA, 2008).…”