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PURPOSE: Açai pulp is a source of phytochemicals and has been associated with antioxidant, anti-inflammatory, and antigenotoxic effects. This study aimed to assess the effects of açai pulp consumption on oxidative, inflammatory, and aerobic capacity markers of cyclist athletes. RESEARCH METHODS AND PROCEDURES: A crossover, randomized, placebo-controlled, single-blind study was developed with ten male cyclists (33.5 ± 4.7 years old, body mass index of 23.9 ± 1.38 kg/m2, and training load around 1875 ± 238 AU/week). The athletes consumed 400 g/day of pasteurized açai pulp (AP) or placebo (PL) for 15 days, with a 30-day wash-out period between trials. Lipid peroxidation, serum antioxidant capacity, DNA damage in peripheral blood (Comet assay), IL-6 and TNF-alpha, blood lactate concentration during effort, anaerobic threshold intensity (ATi), maximum workload reached (Wmax), rating of perceived exertion threshold (RPET), and heart rate threshold (HRT) were evaluated before and after each intervention. Data were analyzed using a linear regression model with mixed effects (p ≤ 0.05). RESULTS: Increased serum antioxidant capacity (p = 0.006) and decreased lipid peroxidation (p = 0.01) were observed in subjects after intervention with AP. Blood lactate levels during effort significantly decreased (by 29%, p = 0.025) and ATi increased (p = 0.006) after AP. No significant effect on DNA damage was attributed to AP consumption. CONCLUSION: We found notable effects of AP intervention on antioxidant status in athletes. Both the reduction in blood lactate concentration and increase in ATi during the effort suggest an overall improvement in the aerobic capacity of the cyclists, confirming that AP consumption may influence variables associated with performance in endurance athletes.
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Antioxidantes , Estrés Oxidativo , Adulto , Suplementos Dietéticos , Humanos , Lactatos , Masculino , Método Simple CiegoRESUMEN
DNA damage and inflammation are promising targets in disease prevention studies. Since these pathways have shown to be modulated by dietary components, investigating the molecular effects of food becomes relevant. This study aimed at investigating the protective effects of cocoplum (Chrysobalanus icaco L.) against doxorubicin (DXR)-induced damage. Rats were treated with cocoplum (100, 200 or 400mg/kg/day) for 14days, associated or not with DXR (15mg/kg b.w.). Tissue-targeted comet assay and the oxidative stress parameters oxidized/reduced glutathione and catalase were investigated in liver, kidney, and heart. The expressions of DNA damage/repair (Gadd45a, Parp1, Xrcc2) and proinflammatory genes (Il-1ß, Il-6, Nf-κb, Tnf-α) were performed by real-time quantitative PCR. Cocoplum decreased DNA damage and the expressions of Gadd45a, Il-1ß, and Tnf-α induced by DXR. These findings demonstrate that cocoplum fruits possess antigenotoxic and anti-inflammatory effects against DXR-induced damage and encourage other in vivo/clinical studies with this fruit.
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Antiinflamatorios/farmacología , Antimutagênicos/farmacología , Proteínas de Ciclo Celular/metabolismo , Chrysobalanaceae/química , Daño del ADN/efectos de los fármacos , Doxorrubicina/toxicidad , Interleucina-1beta/metabolismo , Proteínas Nucleares/metabolismo , Extractos Vegetales/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Antiinflamatorios/aislamiento & purificación , Antimutagênicos/aislamiento & purificación , Catalasa/metabolismo , Proteínas de Ciclo Celular/genética , Ensayo Cometa , Regulación hacia Abajo , Glutatión/metabolismo , Interleucina-1beta/genética , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Proteínas Nucleares/genética , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Ratas Wistar , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
SCOPE: Micronutrients are in small amounts in foods, act in concert, and require variable amounts of time to see changes in health and risk for disease. These first principles are incorporated into an intervention study designed to develop new experimental strategies for setting target recommendations for food bioactives for populations and individuals. METHODS AND RESULTS: A 6-week multivitamin/mineral intervention is conducted in 9-13 year olds. Participants (136) are (i) their own control (n-of-1); (ii) monitored for compliance; (iii) measured for 36 circulating vitamin forms, 30 clinical, anthropometric, and food intake parameters at baseline, post intervention, and following a 6-week washout; and (iv) had their ancestry accounted for as modifier of vitamin baseline or response. The same intervention is repeated the following year (135 participants). Most vitamins respond positively and many clinical parameters change in directions consistent with improved metabolic health to the intervention. Baseline levels of any metabolite predict its own response to the intervention. Elastic net penalized regression models are identified, and significantly predict response to intervention on the basis of multiple vitamin/clinical baseline measures. CONCLUSIONS: The study design, computational methods, and results are a step toward developing recommendations for optimizing vitamin levels and health parameters for individuals.
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Micronutrientes/administración & dosificación , Vitaminas/sangre , Adolescente , Niño , Dislipidemias/sangre , Conducta Alimentaria , Femenino , Humanos , Individualidad , MasculinoRESUMEN
The increasing production of silver nanoparticles (AgNPs) and titanium dioxide nanoparticles (TiO2NPs) has resulted in their elevated concentrations in the environment. This study was, therefore, aimed at determining the distribution, redox parameters, and genotoxic effects in male Wistar rats that were treated with either AgNP or TiO2NP individually, as well as under a co-exposure scenario. Animals were exposed via oral gavage to either sodium citrate buffer (vehicle), 0.5 mg/kg/day TiO2NP, 0.5 mg/kg/day AgNP or a mixture of TiO2NPs and AgNPs. Exposure lasted 45 days after which rats were sacrificed, and tissue biodistribution of Ag and Ti measured. The blood concentration of glutathione (GSH) and activities of glutathione peroxidase (GPx) and catalase (CAT) were determined while the genotoxicity was analyzed using the comet assay in peripheral blood and liver cells. The tissue concentrations of Ag followed the order; blood > liver > kidneys while for Ti the order was kidneys > liver > blood. There was no significant change in the measured redox parameters in animals that were exposed to TiO2NPs. However, there was a significant increase in GSH levels accompanied by a reduction in the GPx activity in AgNP-treated and co-exposed groups. The individual or co-exposure to TiO2NP and AgNP did not markedly induce genotoxicity in blood or liver cells. Data showed that TiO2NP did not produce significant oxidative stress or genotoxicity in rats at the dose used in this study while the same dose level of AgNPs resulted in oxidative stress, but no noticeable adverse genotoxic effects.
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Contaminantes Ambientales/toxicidad , Nanopartículas del Metal/toxicidad , Plata/toxicidad , Titanio/toxicidad , Animales , Análisis Químico de la Sangre , Daño del ADN , Masculino , Oxidación-Reducción , Ratas , Ratas Wistar , Distribución TisularRESUMEN
Some important environmental factors that influence the development of cardiovascular diseases (CVD) include tobacco, excess alcohol, and unhealthy diet. Methionine obtained from the diet participates in the synthesis of DNA, proteins, lipids and affects homocysteine levels, which is associated with the elevated risk for CVD development. Therefore, the aim of this study was to investigate the manner in which dietary methionine might affect cellular mechanisms underlying CVD occurrence. Swiss albino mice were fed either control (0.3% DL-methionine), methionine-supplemented (2% DL-methionine), or a methionine-deprived diet (0% DL-methionine) over a 10-week period. The parameters measured included plasma homocysteine concentrations, oxidative stress by reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, levels of inflammatory cytokines IL-1ß, TNF-α, and IL-6, as well as expression of genes associated with CVD. The levels of apolipoprotein A5 (APOA5), a regulator of plasma triglycerides, were measured. The methionine-supplemented diet increased oxidative stress by lowering the GSH/GSSG ratio in heart tissues and decreased expression of the genes Apob, Ctgf, Serpinb2, Spp1, Il1b, and Sell, but elevated expression of Thbs4, Tgfb2, Ccr1, and Vegfa. Methionine-deprived diet reduced expression of Col3a1, Cdh5, Fabp3, Bax, and Hbegf and increased expression of Sell, Ccl5, Itga2, Birc3, Msr1, Bcl2a1a, Il1r2, and Selp. Methionine-deprived diet exerted pro-inflammatory consequences as evidenced by elevated levels of cytokines IL-1ß, TNF-α, and IL-6 noted in liver. Methionine-supplemented diet increased hepatic IL-6 and cardiac TNF-α. Both methionine supplementation and deprivation lowered hepatic levels of APOA5. In conclusion, data demonstrated that a methionine-supplemented diet modulated important biological processes associated with high risk of CVD development.
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Enfermedades Cardiovasculares/prevención & control , Citocinas/metabolismo , Suplementos Dietéticos , Regulación de la Expresión Génica , Corazón/fisiología , Hígado/fisiología , Metionina , Animales , Biomarcadores/sangre , Enfermedades Cardiovasculares/etiología , Dieta , Femenino , Homocisteína/sangre , Hígado/metabolismo , Ratones , Miocardio/metabolismo , Estrés OxidativoRESUMEN
Phomoxanthone A (PhoA) is a compound isolated from the endophytic fungus Phomopsis longicolla, associated with marine algae Bostrychia radicans. Although this metabolite was previously described regarding its high biological potential, there are no reports concerning the effects of this compound on DNA integrity. This study aimed to evaluate, in lymphocytes and promyelocytic leukemia HL60 cells, the cytotoxicity of this compound through MTT and neutral red (NR) assays, as well as its genotoxicity and mutagenicity by alkaline comet assay and cytokinesis-block micronucleus cytome assay (CBMN-Cyt), respectively. Cells were treated with PhoA concentrations ranging from 0.01 to 100.0µg/mL, and the results show that this molecule did not exhibit cytotoxicity, genotoxicity or mutagenicity in lymphocytes at any tested concentration. Furthermore, PhoA was highly cytotoxic, genotoxic and mutagenic to HL60 cells, establishing a differential response of this natural product in normal and cancer cells. PhoA was highly selective towards HL60 compared to lymphocytes, causing no damage in the latter cell line, suggesting that this compound could be a promising compound in antitumoral drug development.
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Antineoplásicos/toxicidad , Mutágenos/toxicidad , Xantonas/toxicidad , Adolescente , Adulto , Antineoplásicos/aislamiento & purificación , Ascomicetos/química , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ensayo Cometa , Femenino , Células HL-60 , Humanos , Linfocitos/efectos de los fármacos , Masculino , Pruebas de Micronúcleos , Mutágenos/aislamiento & purificación , Xantonas/aislamiento & purificación , Adulto JovenRESUMEN
Chrysobalanus icaco L. is an underexplored plant found in tropical areas around the globe. Currently, there is no apparent information regarding the effects C. icaco fruits may exert in vivo or potential role in health promotion. This study aimed at providing evidence regarding the in vivo influence of this fruit on antigenotoxicity, antimutagenicity, and oxidative stress in rats. Male Wistar rats were treated with 100, 200, or 400 mg/kg body weight (bw)/d C. icaco fruit for 14 d. Doxorubicin (DXR, 15 mg/kg bw, ip) was used for DNA damaging and as an oxidant to generate reactive oxygen species (ROS). Genomic instability was assessed by the comet assay and micronucleus (MN) test, while antioxidant activity was determined by oxidative burst of neutrophils. Chrysobalanus icaco fruit polyphenols were quantified and characterized by high-performance liquid chromatography coupled to a diode array detector and tandem mass spectrometer (HPLC-DAD-MS/MS). The concentrations of 19 chemical elements were determined by inductively coupled plasma-mass spectroscopy (ICP-MS). Significant amounts of polyphenols, magnesium, and selenium were found in C. icaco fruit. This fruit displayed in vivo antioxidant activity against DXR-induced damage in rat peripheral blood neutrophils, antigenotoxicity in peripheral blood cells, and antimutagenicity in bone-marrow cells and peripheral blood cells. Correlation analyses between endpoints examined indicated that the mechanism underlying chemopreventive actions of C. icaco fruit was attributed to inhibition of NADPH oxidase complex manifested as low levels of DNA damage in animals exposed to DXR. Data indicate that phytochemicals and minerals in C. icaco fruit protect DNA against damage in vivo associated with their antioxidant properties.
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Antioxidantes/farmacología , Chrysobalanaceae/química , Daño del ADN/efectos de los fármacos , NADPH Oxidasas/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Doxorrubicina/toxicidad , Frutas/química , Masculino , Sustancias Protectoras/farmacología , Ratas , Ratas WistarRESUMEN
Deficiency of vitamin D3, a lipophilic micronutrient, plays a role in the development of some chronic diseases. Vitamin D3 deficiency affects 25-50% of the human population and has been associated with increased risk for development of hypertension. DNA damage induced by reactive oxygen species (ROS) occurs more often in hypertensive than in normotensive individuals, and vitamin D3 status can influence this relationship. The aim of this study was to evaluate whether a diet supplemented with (10,000 IU/kg) or deficient in (0 IU/kg) vitamin D3, compared to a vitamin D3 control diet (1000 IU/kg), would modulate DNA damage and ROS production in spontaneously hypertensive rats (SHR) and normotensive control Wistar-Kyoto (WKY) rats after 12 weeks of treatment. ROS production was assessed by measuring the oxidative burst of neutrophils. DNA damage was evaluated using the comet assay in peripheral blood and the micronucleus test in bone marrow and peripheral blood. Vitamin D3 supplementation did not induce DNA damage and did not change neutrophil ROS production in SHR and WKY rats. Vitamin D3 deficiency induced neutrophil ROS production and a high frequency of micronucleus formation in the bone marrow and peripheral blood of SHR rats only, and induced DNA damage (comet) in peripheral blood of both SHR and WKY rats. In conclusion, vitamin D3 deficiency showed a more pronounced effect on hypertensive animals. Population studies are needed to test whether this relationship also exists in humans.
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Colecalciferol/deficiencia , Hipertensión/etiología , Neutrófilos/metabolismo , Animales , Colecalciferol/fisiología , Colecalciferol/uso terapéutico , Daño del ADN , Suplementos Dietéticos , Modelos Animales de Enfermedad , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Hipertensión/metabolismo , Masculino , Neutrófilos/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Especies Reactivas de Oxígeno , Estallido RespiratorioRESUMEN
SCOPE: Vitamin B6 plays crucial roles on brain development and its maternal deficiency impacts the gamma-aminobutyric acid (GABA)ergic, serotonergic, glutamatergic, and dopaminergic systems in offspring. However, the molecular mechanisms underlying these neurological changes are not well understood. Thus, we aimed at evaluating which components of those neurotransmitter metabolism and signaling pathways can be modulated by maternal vitamin B6 -deficient or B6 -supplementated diets in the hippocampus of rat dams and their offspring. METHODS AND RESULTS: Female Wistar rats were fed three different diets: control (6 mg vitamin B6 /kg), supplemented (30 mg vitamin B6 /kg) or deficient diet (0 mg vitamin B6 /kg), from 4 weeks before pregnancy through lactation. Newborn pups (10 days old) from rat dams fed vitamin B6 -deficient diet presented hyperhomocysteinemia and had a significant increase in mRNA levels of glutamate decarboxylase 1 (Gad1), fibroblast growth factor 2 (Fgf2), and glutamate-ammonia ligase (Glul), while glutaminase (Gls) and tryptophan hydroxylase 1 (Tph1) mRNAs were downregulated. Vitamin B6 supplementation or deficiency did not change hippocampal global DNA methylation. CONCLUSION: A maternal vitamin B6 -deficient diet affects the expression of genes related to GABA, glutamate, and serotonin metabolisms in offspring by regulating Gad1, Glul, Gls, and Tph1 mRNA expression.
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Hipocampo/efectos de los fármacos , Deficiencia de Vitamina B 6/sangre , Vitamina B 6/administración & dosificación , Vitamina B 6/sangre , Animales , Animales Recién Nacidos , Metilación de ADN , Suplementos Dietéticos , Femenino , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Regulación de la Expresión Génica , Glutamato Descarboxilasa/genética , Glutamato Descarboxilasa/metabolismo , Glutamato-Amoníaco Ligasa/genética , Glutamato-Amoníaco Ligasa/metabolismo , Ácido Glutámico/metabolismo , Glutaminasa/genética , Glutaminasa/metabolismo , Hipocampo/metabolismo , Homocisteína/sangre , Ratas , Ratas Wistar , Serotonina/metabolismo , Triptófano Hidroxilasa/genética , Triptófano Hidroxilasa/metabolismo , Deficiencia de Vitamina B 6/tratamiento farmacológico , Ácido gamma-Aminobutírico/metabolismoRESUMEN
In this study, we assessed whether weight gain influenced the systemic lupus erythematosus (SLE) onset and/or outcome, and examined the role that reactive oxygen species (ROS) production by neutrophils played in the SLE onset and/or outcome. Female control (C57BL/6) and lupus-prone B6.MRL/lpr mice (CM and LPM, respectively) at 4 weeks old were fed standard diet or standard diet plus cafeteria diet during 12 weeks. SLE diagnosis relied on the presence of both antinuclear antibodies (ANA) and renal abnormalities. We found that the percentage of weight gain in CM and LPM increased as a function of the length of cafeteria diet feeding period, but it was not associated with energy intake. Cafeteria diet-fed CM and LPM at 8 and 12 weeks old were overweight, while CM and LPM at 16 weeks old were obese. Compared with standard diet-fed CM and LPM, cafeteria diet-fed CM and LPM exhibited elevated glucose and total cholesterol levels, and diminished triglycerides levels. Standard diet-fed 16-week-old LPM and cafeteria diet-fed 12-week-old LPM had nephritis, characterized by the increased interstitial infiltration of leukocytes. Cafeteria diet-induced weight gain rose the frequency of homogeneous and speckled ANA staining patterns in the 12- and 16-week-old LPM groups. Together, these results indicated that weight gain anticipated the SLE onset. In addition, neutrophils from cafeteria diet-fed 8-week-old LPM exhibited augmented ROS production capacity; in standard diet-fed LPM, such rise occurred only in the 16-week-old group. Thus, the neutrophil ROS production capacity was increased before the SLE onset and during its outcome. Overweight and obese CM and LPM displayed elevated levels of kidney, liver, heart, and spleen lipid peroxidation. In conclusion, cafeteria diet-induced weight gain is associated with the increased production of ANA and neutrophil-derived ROS, which may contribute to accelerate the SLE onset.
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Lupus Eritematoso Sistémico/inmunología , Neutrófilos/metabolismo , Edad de Inicio , Animales , Anticuerpos Antinucleares/sangre , Dieta Occidental/efectos adversos , Femenino , Riñón/patología , Peroxidación de Lípido , Hígado/patología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/patología , Ratones Endogámicos C57BL , Ratones Endogámicos MRL lpr , Estrés Oxidativo , Estallido Respiratorio , Aumento de PesoRESUMEN
Brazilian savanna constitutes a valuable ecoregion that contributes to the supply of fruit known worldwide for its nutritional value and peculiar flavors. Among them, the Marolo (Annona crassiflora Mart.) fruit is known for its use in folk medicine. In order to establish the safety of Marolo for human consumption, this study evaluated the following: the chemical composition of Marolo pulp; its mutagenic and antimutagenic activities using micronucleus test; and the oxidative stress induced in the livers of mice fed a diet containing 1%, 10% or 20% pulp. It was observed that the chemical composition of marolo pulp was similar to that of common fruit; nevertheless, its lipidic content and energetic values were higher. In the mice fed experimental diets, the biochemical parameters of the blood serum showed normal levels of glucose, triglycerides, and cholesterol. The micronucleus test indicated neither mutagenic nor antimutagenic effects of Marolo consumption on bone marrow cells but showed potentialization of cyclophosphamide (CP). The oxidative stress levels observed indicated that CP was not exerting a great influence on the induction of reactive oxygen species. As the whole fruit is a complex matrix, the interactions between its components could be responsible for its negative and positive biological effects.