Effect of lycopene on doxorubicin-induced cardiotoxicity: an echocardiographic, histological and morphometrical assessment.
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.
Anjos Ferreira
Ana Lucia
AL
Department of Internal Medicine, Botucatu Faculty of Medicine, Universidade Estadual Paulista, São Paulo State University, Botucatu, SP, Brazil. ferreira@fmb.unesp.br
Russell
Robert Mitchell
RM
Rocha
Noeme
N
Placido Ladeira
Marcelo Sady
MS
Favero Salvadori
Daisy Maria
DM
Oliveira Nascimento
Maria Carolina Munhoz
MC
Matsui
Mirna
M
Carvalho
Flavio Augusto
FA
Tang
Guangwen
G
Matsubara
Luiz Shiguero
LS
Matsubara
Beatriz Bojikian
BB
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology*; D002338:Carotenoids / Q000493:pharmacokinetics / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000633:toxicity*; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D000077276:Lycopene; D008297:Male; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D002338:Carotenoids; D004317:Doxorubicin; D000077276:Lycopene