Ferreira Ana Lucia Anjos, Salvadori Daisy Maria Favero, Nascimento Maria Carolina Munhoz Oliveira, Rocha Noeme Souza, Correa Camila R, Pereira Elenize Jamas, Matsubara Luiz Shiguero, Matsubara Beatriz Bojikian, Ladeira Marcelo Sady Plácido
Department of Internal Medicine, Botucatu Faculty of Medicine, UNESP, São Paulo State University, Botucatu, Brazil.
Mutat Res. 2007 Jul 10;631(1):26-35. doi: 10.1016/j.mrgentox.2007.04.003. Epub 2007 Apr 7.
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.
阿霉素(DOX)是一种有效的化疗药物,可用于治疗多种类型的肿瘤;然而,由于其严重的心脏毒性,其应用受到限制。由于人们认为活性氧参与了DOX诱导的心脏毒性,因此抗氧化剂已被用于减轻其副作用。为了确定番茄红素对DOX诱导的心脏氧化DNA损伤的保护作用,我们将Wistar雄性大鼠分为对照组(C)、番茄红素组(L)、DOX组(D)和DOX+番茄红素组(DL)。它们通过灌胃接受玉米油(C组和D组)或番茄红素(5mg/kg体重/天)(L组和DL组),持续7周。在第3、4、5和6周时,它们还通过腹腔注射接受生理盐水(C组和L组)或DOX(4mg/kg体重)(D组和DL组)。通过高效液相色谱法检测番茄红素的吸收情况。使用甲酰胺嘧啶-DNA糖基化酶(FPG)和核酸内切酶III(endo III)通过碱性彗星试验评估心脏氧化DNA损伤。与其他组相比,D组大鼠心肌细胞中SBs、SBs FPG和SBs Endo III的水平更高。与C组和L组相比时,DL组心肌细胞中的DNA损伤水平没有差异。D组或DL组心肌细胞活力低于C组或L组(p<0.01)。L组(47.43±11.78)和DL组(49.85±16.24)皂化心脏中的番茄红素水平(平均值±标准差,nmol/kg)相似。我们的结果表明:(I)通过心脏中的水平证实了番茄红素的吸收;(2)DOX诱导心肌细胞氧化DNA损伤;(3)补充番茄红素可保护心肌细胞免受氧化DNA损伤。