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Title: Effect of Lycopene on doxorubicin-induced cardiotoxicity: An echocardiographic, histological, and morphometrical assessment

Author
item FERREIRA, ANA L - UNESP, BOTUCATU, BRASIL
item Russell, Robert
item ROCHA, NOEME - UNESP, BOTUCATU, BRASIL
item LADEIRA, MARCELO - UNESP, BOTUCATU, BRASIL
item SALVADORI, DAISY - UNESP, BOTUCATU, BRASIL
item NASCIMIENTO, MARIA - UNESP, BOTUCATU, BRASIL
item MATSUI, MIRNA - UNESP, BOTUCATU, BRASIL
item CARVALHO, FLAVIO - UNESP, BOTUCATU, BRASIL
item Tang, Guang-Wen
item MATSUBARA, LUIZ - UNESP, BOTUCATU, BRASIL
item MATSUBARA, BEATRIZ - UNESP, BOTUCATU, BRASIL

Submitted to: Pharmacology and Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/2/2007
Publication Date: 7/1/2007
Citation: Ferreira, A., Russell, R., Rocha, N., Ladeira, M.S., Salvadori, D.M., Nascimiento, M.C., Matsui, M., Carvalho, F., Tang, G., Matsubara, L.S., Matsubara, B. 2007. Effect of Lycopene on doxorubicin-induced cardiotoxicity: An echocardiographic, histological, and morphometrical assessment. Pharmacology and Toxicology. 101:16-24.

Interpretive Summary: The common denominator of many anti-cancer drugs is that their action is mediated in part by reactive oxygen species. Lycopene is one of the most potent antioxidants among the dietary carotenoids. The question to be answered is whether lycopene could protect against cardiotoxicity induced by the anti-cancer drug (doxorubicin). We found on microscopic examination of tissue that the heart cell damage which doxorubicin induced was significantly suppressed in rats pretreated with lycopene. This work represents a classic example of a nutrient ameliorating bad side effects of a drug. Some of the anti-tumor activity of the drug is evidently related to free radical production; therefore it is not clear whether the antioxidant treatment in the form of lycopene might also interfere with the drugs anti-tumor activity.

Technical Abstract: To determine if lycopene protects against cardiotoxicity induced by doxorubicin, male Wistar rats were distributed in Control (C), Lycopene (L), Doxorubicin (D) and Doxorubicin + Lycopene (DL) groups. 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. Conclusions: 1) Lycopene absorption was confirmed by its levels in tissues and plasma; 2) Doxorubicin-induced cardiotoxicity was confirmed by echocardiogram and morphological analysis; 3) Lycopene supplementation provided myocyte protection without preventing interstitial collagen accumulation increase; 4) Lycopene depletion was not observed in plasma and tissues from DL group.