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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 (C), Lycopene (L), Doxorubicin (D) or Doxorubicin + Lycopene (DL) group. They received corn oil (C, D) or lycopene (5 mg/Kg body wt / day) (L, DL) by gavage for a 7-week period. They also received saline (C, L) or doxorubicin (4 mg/Kg) (D, DL) intraperitoneally at 3rd, 4th, 5th, and at 6th week. Animals underwent echocardiogram and were killed for tissue analyses at 7th week. Mean lycopene levels (nmol/Kg) in liver were higher in DL (5822.59) than in L (2496.73), but no differences in lycopene were found in heart or plasma of these 2 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 showed: 1) Doxorubicin-induced cardiotoxicity was confirmed by echocardiogram and morphological evaluations; 2) Lycopene absorption was confirmed by its levels in heart, liver and plasma; 3) Lycopene supplementation provided myocyte protection without preventing interstitial collagen accumulation increase; 4) Doxorubicin-induced cardiac dysfunction was not prevented by lycopene supplementation; 5) Lycopene depletion was not observed in plasma and tissues from animals treated with doxorubicin. (AU)

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