Influence of orange juice over the genotoxicity induced by alkylating agents: an in vivo analysis.

Curso de Nutrição, Departamento de Educação Física e Saúde, Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, RS, Brazil.
Mutagenesis (Impact Factor: 3.5). 08/2005; 20(4):279-83. DOI: 10.1093/mutage/gei034
Source: PubMed

ABSTRACT There is considerable epidemiological evidence indicating an association between diets rich in fresh fruit and vegetables and a decreased incidence of cancers. Methyl methanesulfonate (MMS) and cyclophosphamide (CP) are alkylating agents that differ in their mode of action. MMS is a directly-acting, monofunctional agent, while CP is a bifunctional agent that requires metabolic activation to a reactive metabolite. To evaluate if orange juice could reduce DNA damage induced by these alkylating agents, mice were treated orally (by gavage) with MMS and CP, prior to and after treatment with orange juice. DNA damage was evaluated by the comet assay in peripheral white blood cells. Under these experimental conditions, orange juice reduced the extent of DNA damage caused by both mutagens. For MMS, the antigenotoxic effect of the orange juice was both protective (orange juice pre-treatment) and reparative (orange juice post-treatment); for CP, the effect was reparative only. The components of orange juice can have several biological effects, including acting as targets of toxicants and modulating metabolization/detoxification routes. Considering the different mechanisms of the action of the two drugs, different protective effects are suggested. These results demonstated the ability of the in vivo comet assay to detect in vivo modulation of MMS and CP mutagenicity by orange juice.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The antioxidant and free radical scavenger properties of melatonin have been well described in the literature. In this study, our objective was to determine the protective effect of the pineal gland hormone against the DNA damage induced by cyclophosphamide (CP), an anti-tumor agent that is widely applied in clinical practice. DNA damage was induced in rats by a single intraperitoneal injection of CP (20 or 50 mg/kg). Animals received melatonin during the dark period for 15 days (1 mg/kg in the drinking water). Rat bone marrow cells were used for the determination of chromosomal aberrations and of formamidopyrimidine DNA glycosylase enzyme (Fpg)-sensitive sites by the comet technique and of Xpf mRNA expression by qRT-PCR. The number (mean ± SE) of chromosomal aberrations in pinealectomized (PINX) animals treated with melatonin and CP (2.50 ± 0.50/100 cells) was lower than that obtained for PINX animals injected with CP (12 ± 1.8/100 cells), thus showing a reduction of 85.8% in the number of chromosomal aberrations. This melatonin-mediated protection was also observed when oxidative lesions were analyzed by the Fpg-sensitive assay, both 24 and 48 h after CP administration. The expression of Xpf mRNA, which is involved in the DNA nucleotide excision repair machinery, was up-regulated by melatonin. The results indicate that melatonin is able to protect bone marrow cells by completely blocking CP-induced chromosome aberrations. Therefore, melatonin administration could be an alternative and effective treatment during chemotherapy.
    Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 03/2013; · 1.08 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Orange juice (OJ) is among the most consumed fruit juices worldwide, and its chemopreventive action is fairly addressed in the literature. This review critically presents the available evidence linking OJ with cancer chemoprevention and on discussing the putative mechanisms and negative health effects. The chemopreventive action of OJ is related to its effect on metabolic enzymes and its antiinflammatory, cytoprotective/apoptotic, hormonal, cell signaling-modulating, antioxidant, and antigenotoxic effects. Most studies on OJ are in vitro, and few are conducted in vivo. Results from in vitro studies must be interpreted carefully because these findings do not consider in vivo bioavailability. However, such results are useful for studying the impact of different processing and storage methods on OJ's chemopreventive effect. Evidence of OJ's chemoprevention in humans is limited. OJ is antimutagenic in bacteria and antigenotoxic in humans and rodents. Studies using rodent cancer models showed that OJ is cancer chemopreventive, influencing either the induction stage or the promotion stage. The composition and, therefore, the chemopreventive action of OJ might be influenced by different cultivars, climates, extraction methods, packaging, storage temperatures, and shelf lives, among other factors. Epidemiological studies and randomized controlled intervention studies in humans evaluating the chemopreventive effect of OJ, taking into consideration variability in OJ composition, are needed.
    Nutrition and Cancer 08/2013; · 2.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Excessive release of stress hormone adrenaline is accompanied by generation of reactive oxygen species which may cause disruption of DNA integrity leading to cancer and age-related disorders. Phenolic-rich plant product dry olive leaf extract (DOLE) is known to modulate effects of various oxidants in human cells. The aim was to evaluate the effect of commercial DOLE against adrenaline induced DNA damage in human leukocytes by using comet assay. Peripheral blood leukocytes from 6 healthy subjects were treated in vitro with three final concentrations of DOLE (0.125, 0.5, and 1 mg/mL) for 30 min at 37°C under two different protocols, pretreatment and post-treatment. Protective effect of DOLE was assessed from its ability to attenuate formation of DNA lesions induced by adrenaline. Compared to cells exposed only to adrenaline, DOLE displayed significant reduction (P<0.001) of DNA damage at all three concentrations and under both experimental protocols. Pearson correlation analysis revealed a significant positive association between DOLE concentration and leukocytes DNA damage (P<0.05). Antigenotoxic effect of the extract was more pronounced at smaller concentrations. Post-treatment with 0.125 mg/mL DOLE was the most effective against adrenaline genotoxicity. Results indicate genoprotective and antioxidant properties in dry olive leaf extract, strongly supporting further explorations of its underlying mechanisms of action.
    Toxicology in Vitro 01/2014; · 2.65 Impact Factor


Available from
May 20, 2014