title: 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.
authors.affiliation: Department of Internal Medicine, Botucatu Faculty of Medicine, Universidade Estadual Paulista, São Paulo State University, Botucatu, SP, Brazil. ferreira@fmb.unesp.br
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Anjos Ferreira
authors.forename: Robert Mitchell
authors.initials: RM
authors.lastname: Russell
authors.forename: Noeme
authors.initials: N
authors.lastname: Rocha
authors.forename: Marcelo Sady
authors.initials: MS
authors.lastname: Placido Ladeira
authors.forename: Daisy Maria
authors.initials: DM
authors.lastname: Favero Salvadori
authors.forename: Maria Carolina Munhoz
authors.initials: MC
authors.lastname: Oliveira Nascimento
authors.forename: Mirna
authors.initials: M
authors.lastname: Matsui
authors.forename: Flavio Augusto
authors.initials: FA
authors.lastname: Carvalho
authors.forename: Guangwen
authors.initials: G
authors.lastname: Tang
authors.forename: Luiz Shiguero
authors.initials: LS
authors.lastname: Matsubara
authors.forename: Beatriz Bojikian
authors.initials: BB
authors.lastname: Matsubara
mesh_terms: 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
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D002338:Carotenoids; D004317:Doxorubicin; D000077276:Lycopene