title: Tomato-oleoresin supplement prevents doxorubicin-induced cardiac myocyte oxidative DNA damage in rats.
abstract: Doxorubicin (DOX) is an efficient chemotherapeutic agent used against several types of tumors; however, its use is limited due to severe cardiotoxicity. Since it is accepted that reactive oxygen species are involved in DOX-induced cardiotoxicity, antioxidant agents have been used to attenuate its side effects. To determine tomato-oleoresin protection against cardiac oxidative DNA damage induced by DOX, we distributed Wistar male rats in control (C), lycopene (L), DOX (D) and DOX+lycopene (DL) groups. They received corn oil (C, D) or tomato-oleoresin (5mg/kg body wt. day) (L, DL) by gavage for a 7-week period. They also received saline (C, L) or DOX (4mg/kg body wt.) (D, DL) intraperitoneally at the 3rd, 4th, 5th, and at 6th week. Lycopene absorption was checked by HPLC. Cardiac oxidative DNA damage was evaluated by the alkaline Comet assay using formamidopyrimidine-DNA glycosylase (FPG) and endonuclease III (endo III). Cardiomyocyte levels of SBs, SBs FPG and SBs Endo III were higher in rats from D when compared to other groups. DNA damage levels in cardiomyocytes from DL were not different when compared to C and L groups. The viability of cardiomyocytes from D or DL was lower than C or L groups (p<0.01). Lycopene levels (mean+/-S.D.nmol/kg) in saponified hearts were similar between L (47.43+/-11.78) and DL (49.85+/-16.24) groups. Our results showed: (1) lycopene absorption was confirmed by its cardiac levels; (2) DOX-induced oxidative DNA damage in cardiomyocyte; (3) tomato-oleoresin supplementation protected against cardiomyocyte oxidative DNA damage.
authors.affiliation: Department of Internal Medicine, Botucatu Faculty of Medicine, UNESP, São Paulo State University, Botucatu, Brazil. ferreira@fmb.unesp.br
authors.forename: Ana Lucia Anjos
authors.initials: AL
authors.lastname: Ferreira
authors.forename: Daisy Maria Favero
authors.initials: DM
authors.lastname: Salvadori
authors.forename: Maria Carolina Munhoz Oliveira
authors.initials: MC
authors.lastname: Nascimento
authors.forename: Noeme Souza
authors.initials: NS
authors.lastname: Rocha
authors.forename: Camila R
authors.initials: CR
authors.lastname: Correa
authors.forename: Elenize Jamas
authors.initials: EJ
authors.lastname: Pereira
authors.forename: Luiz Shiguero
authors.initials: LS
authors.lastname: Matsubara
authors.forename: Beatriz Bojikian
authors.initials: BB
authors.lastname: Matsubara
authors.forename: Marcelo Sady Plácido
authors.initials: MS
authors.lastname: Ladeira
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology; D020552:Comet Assay; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D019587:Dietary Supplements / Q000032:analysis; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004706:Endodeoxyribonucleases / Q000378:metabolism; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D010936:Plant Extracts; C018620:oleoresins; D002338:Carotenoids; D004317:Doxorubicin; D004706:Endodeoxyribonucleases; D045647:DNA Glycosylases; D000077276:Lycopene