RESUMO
The purpose of the present study was to examine the nutraceutical potential of choline as an added value to its well-known brain nutrient role. Several toxicity, antitoxicity, genotoxicity, antigenotoxicity, and longevity endpoints were checked in the somatic mutation and recombination test in in vivo Drosophila animal model. Cytotoxicity in human leukemia-60 cell line (HL-60) promyelocytic and NIH3T3 mouse fibroblast cells, proapoptotic DNA fragmentation, comet assay, methylation status, and macroautophagy (MA) activity were tested in in vitro assays. Choline is not only safe but it is also able to protect against the DNA damage caused by an oxidative genotoxin. Moreover, it improves the life extension in the animal model. The in vitro results show that it is able to exhibit genetic damage against leukemia HL-60 cells. Single-strand breaks in DNA are observed at the molecular level in treatments with choline, although only a significant hypermethylation on the long interspersed elements-1 and a hypomethylation on the satellite-alpha DNA repetitive DNA sequences of HL-60 cells at the lowest concentration (0.447 mM) were observed. Besides, choline decreased MA at the lower assayed concentration and the MA response to topoisomerase inhibitor (etoposide) is maintained in the presence of treatment with 0.22 mM choline. Taking into account the hopeful results obtained in the in vivo and in vitro assays, choline could be proposed as a substance with an important nutraceutical value for different purposes.
Assuntos
Colina/farmacologia , Dano ao DNA/efeitos dos fármacos , Animais , DNA/genética , Quebras de DNA/efeitos dos fármacos , Células HL-60 , Humanos , Camundongos , Células NIH 3T3RESUMO
Borage (Borago officinalis L.) seed oil has been used as a treatment for various degenerative diseases. Many useful properties of this oil are attributed to its high gamma linolenic acid content (GLA, 18:3 ω-6). The purpose of this study was to demonstrate the safety and suitability of the use of borage seed oil, along with one of its active components, GLA, with respect to DNA integrity, and to establish possible in vivo toxic and in vitro cytotoxic effects. In order to measure these properties, five types of assays were carried out: toxicity, genotoxicity, antigenotoxicity, cytotoxicity (using the promyelocytic leukaemia HL60 cell line), and life span (in vivo analysis using the Drosophila model). Results showed that i) Borage seed oil is not toxic to D. melanogaster at physiological concentrations below 125 µl/ml and the studies on GLA indicated non-toxicity at the lowest concentration analyzed ii) Borage seed oil and GLA are DNA safe (non-genotoxic) and antimutagenic compared to hydrogen peroxide, thereby confirming its antioxidant capacity; iii) Borage seed oil and GLA exhibited cytotoxic activity in low doses (IC50 of 1 µl/ml and 0.087 mM, respectively) iv) Low doses of borage seed oil (0.19%) increased the health span of D. melanogaster; and v) GLA significantly decreased the life span of D. melanogaster.Based on the antimutagenic and cytotoxic effects along with the ability to increase the health span, we propose supplementation with borage seed oil rather than GLA, because it protects DNA by modulating oxidative genetic damage in D. melanogaster, increases the health span and exerts cytotoxic activity towards promyelocytic HL60 cells.
Assuntos
Borago/química , DNA/efeitos dos fármacos , Drosophila melanogaster/efeitos dos fármacos , Óleos de Plantas/farmacologia , Substâncias Protetoras/farmacologia , Sementes/química , Ácido gama-Linolênico/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Drosophila melanogaster/crescimento & desenvolvimento , Células HL-60 , Humanos , Longevidade/efeitos dos fármacos , Mutagênicos/toxicidade , Mutação/genética , Óleos de Plantas/química , Óleos de Plantas/toxicidade , Recombinação Genética/genética , Tocoferóis/análise , Triglicerídeos/análise , Ácido gama-Linolênico/química , Ácido gama-Linolênico/toxicidadeRESUMO
This study examined global oxidative stress (GOS) and antioxidant system and their correlation with disease stage in 19 patients with HD. The results revealed an increase in oxidative stress biomarkers and a reduction in antioxidant systems in HD patients. The effects were more intense in HD1 than in HD2 patients. Additionally, carbonylated proteins and GOS were correlated with disease stage. These findings suggest that oxidative stress plays an important role in the pathogenesis of HD.
Assuntos
Biomarcadores/metabolismo , Doença de Huntington/metabolismo , Estresse Oxidativo , Adulto , Antioxidantes/metabolismo , Feminino , Humanos , Doença de Huntington/patologia , Masculino , Pessoa de Meia-Idade , Carbonilação ProteicaRESUMO
Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. We have investigated whether the quality of dietary fat alters postprandial cellular oxidative stress and whether the supplementation with coenzyme Q(10) (CoQ) lowers postprandial oxidative stress in an elderly population. In this randomized crossover study, 20 participants were assigned to receive three isocaloric diets for periods of 4 week each: (1) Mediterranean diet supplemented with CoQ (Med+CoQ diet), (2) Mediterranean diet (Med diet), and (3) saturated fatty acid-rich diet (SFA diet). After a 12-h fast, the volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. CoQ, lipid peroxides (LPO), oxidized low-density lipoprotein (oxLDL), protein carbonyl (PC), total nitrite, nitrotyrosine plasma levels, catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and ischemic reactive hyperaemia (IRH) were determined. Med diet produced a lower postprandial GPx activity and a lower decrease in total nitrite level compared to the SFA diet. Med and Med+CoQ diets induced a higher postprandial increase in IRH and a lower postprandial LPO, oxLDL, and nitrotyrosine plasma levels than the SFA diet. Moreover, the Med+CoQ diet produced a lower postprandial decrease in total nitrite and a greater decrease in PC levels compared to the other two diets and lower SOD, CAT, and GPx activities than the SFA diet.In conclusion, Med diet reduces postprandial oxidative stress by reducing processes of cellular oxidation and increases the action of the antioxidant system in elderly persons and the administration of CoQ further improves this redox balance.
Assuntos
Dieta Mediterrânea , Suplementos Nutricionais , Estresse Oxidativo , Período Pós-Prandial , Ubiquinona/análogos & derivados , Vitaminas/administração & dosagem , Idoso , Apolipoproteínas/sangue , Glicemia/análise , Estudos Cross-Over , Gorduras na Dieta/administração & dosagem , Endotélio Vascular/fisiologia , Feminino , Humanos , Insulina/sangue , Fluxometria por Laser-Doppler , Lipídeos/sangue , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ubiquinona/administração & dosagemRESUMO
The acute ingestion of a supplement with different glycemic carbohydrates, including fructose, is a typical practice for athletes before exercising. Observational evidence suggests that different metabolic responses may modify the exercise-stimulated endothelium-dependent vasodilation. The purpose of the present study was to investigate whether endothelial reactivity, stimulated by anaerobic exercise (AnE) or aerobic exercise (AE), both performed with glycemic supplementation, is modified by the addition of fructose. Twenty physically trained men ingested an oral dose of glucose (G) or glucose plus fructose (F) 15 minutes before starting a 30-minute session of AnE (10 sets of 10 repetitions of half squat) or AE (cycling). The combination resulted in 4 randomized interventions in a crossover design in which all subjects performed all experimental conditions: G+AnE, F+AnE, G+AE, and F+AE. Ischemic reactive hyperemia (IRH), glycemia, plasma lipoperoxides (LPOs), nitric oxide (NO), and lactate were determined at baseline, exercise, and acute recovery time points. Immediately after AnE, IRH was 26.35% higher in F+AnE than in G+AnE (p<0.05); this difference rose to 27.24% at the end of the recovery period (p<0.05). The glycemic peak in F+AnE was lower than in G+AnE (p<0.05), and there was a second peak during recovery (p<0.05). There were no differences observed in LPO between anaerobic trials, but the NO bioavailability increased and was higher in F + AnE than in G+AnE after exercise and recovery (p<0.05). Residual lactate was also higher under the F+AnE condition (p<0.05). During AE, there were no differences in IRH, glycemia, or NO between groups, but LPO was significantly higher after F supplementation. These results suggest that the addition of fructose to a single G supplement ingested before a glycolitic exercise can modify the glucoregulation and increases ischemic reactive hyperemia.
Assuntos
Limiar Anaeróbio/efeitos dos fármacos , Carboidratos da Dieta/administração & dosagem , Endotélio Vascular/efeitos dos fármacos , Exercício Físico/fisiologia , Frutose/administração & dosagem , Glucose/administração & dosagem , Vasodilatação/fisiologia , Adulto , Limiar Anaeróbio/fisiologia , Atletas , Glicemia/análise , Suplementos Nutricionais , Endotélio Vascular/fisiologia , Glicólise , Humanos , Insulina/sangue , Ácido Láctico/sangue , Peróxidos Lipídicos/sangue , Masculino , Óxido Nítrico/sangueRESUMO
Previous evidence supports the concept that increased oxidative stress may play an important role in MetS (metabolic syndrome)-related manifestations. Dietary fat quality has been proposed to be critical in oxidative stress and the pathogenesis of the MetS. In the present study, we investigated whether oxidative stress parameters are affected by diets with different fat quantity and quality during the postprandial state in subjects with the MetS. Patients were randomly assigned to one of four isoenergetic diets distinct in fat quantity and quality for 12 weeks: a high-saturated-fatty-acid (HSFA) diet, a high-mono-unsaturated-fatty-acid (HMUFA) diet and two low-fat/high-complex carbohydrate diets [supplemented with 1.24 g/day of long-chain n-3 polyunsaturated fatty acid (LFHCC n-3) or with 1 g/day of sunflower oil high in oleic acid (LFHCC) as placebo]. The HMUFA diet enhanced postprandial GSH (reduced glutathione) levels and the GSH/GSSH (oxidized glutathione) ratio, compared with the other three diets. In addition, after the HMUFA-rich diet postprandial lipid peroxide levels, protein carbonyl concentrations, SOD (superoxide dismutase) activity and plasma H2O2 levels were lower compared with subjects adhering to the HSFA-rich diet. Both LFHCC diets had an intermediate effect relative to the HMUFA and HSFA diets. In conclusion, our data support the notion that the HMUFA diet improves postprandial oxidative stress in patients with the MetS. These findings suggest that the postprandial state is important for understanding the possible cardioprotective effects associated with mono-unsaturated dietary fat, particularly in subjects with the MetS.
Assuntos
Gorduras na Dieta/farmacologia , Síndrome Metabólica/dietoterapia , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/metabolismo , Biomarcadores/sangue , Índice de Massa Corporal , Dieta Mediterrânea , Gorduras na Dieta/administração & dosagem , Gorduras Insaturadas na Dieta/administração & dosagem , Gorduras Insaturadas na Dieta/farmacologia , Ingestão de Energia , Feminino , Glutationa/sangue , Dissulfeto de Glutationa/sangue , Humanos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Período Pós-Prandial/efeitos dos fármacosRESUMO
This study sought to compare the time course changes in oxidative state and glycemic behavior when glucose or glucose plus fructose are consumed before endurance and strength exercise. After two weeks on a controlled diet, 20 physically trained males ingested an oral dose of glucose or glucose plus fructose, 15 min before starting a moderate-intensity 30-min session of endurance or strength exercise. The combination resulted in four randomized interventions: glucose or glucose plus fructose + endurance exercise and glucose or glucose plus fructose + strength exercise, which were implemented consecutively in random order at 1-week intervals. Plasma concentration of lipoperoxides, oxidized LDL, reduced glutathione, catalase and glycemia were determined at baseline, during exercise and acute recovery. Following the ingestion of glucose plus fructose, lipoperoxides, catalase and reduced glutathione depletion were significantly higher than following consumption of glucose, for both endurance and strength exercise (P < 0.05). Oxidized LDL-c was higher after glucose plus fructose than after glucose alone in endurance exercise (P < 0.05). There was no difference in the glycemic peak between glucose plus fructose and glucose ingestion in endurance exercise trials. In strength exercise, the post-absorptive glycemic peak was less when the participants ingested glucose plus fructose than glucose (P < 0.05), and a second peak was found in the recovery phase of this group (P < 0.05). In conclusion, the addition of fructose to a pre-exercise glucose supplement triggers oxidative stress.
Assuntos
Glicemia/metabolismo , Exercício Físico/fisiologia , Frutose/farmacologia , Força Muscular/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Resistência Física/fisiologia , Adulto , Apolipoproteínas B/sangue , Catalase/sangue , LDL-Colesterol/sangue , Glucose/farmacologia , Glutationa/sangue , Índice Glicêmico , Humanos , Peróxidos Lipídicos/sangue , MasculinoRESUMO
The metabolic response when aerobic exercise is performed after the ingestion of glucose plus fructose is unclear. In the present study, we administered two beverages containing GluF (glucose+fructose) or Glu (glucose alone) in a randomized cross-over design to 20 healthy aerobically trained volunteers to compare the hormonal and lipid responses provoked during aerobic exercise and the recovery phase. After ingesting the beverages and a 15-min resting period, volunteers performed 30 min of moderate aerobic exercise. Urinary and blood samples were taken at baseline (t(-15)), during the exercise (t(0), t(15) and t(30)) and during the recovery phase (t(45), t(75) and t(105)). Plasma insulin concentrations were higher halfway through the exercise period and during acute recuperation (t(15) and t(75); P<0.05) following ingestion of GluF than after Glu alone, without any differences between the effects of either intervention on plasma glucose concentrations. Towards the end of the exercise period, urinary catecholamine concentrations were lower following GluF (t(45); P<0.05). Plasma triacylglycerol (triglyceride) concentrations were higher after the ingestion of GluF compared with Glu (t(15), t(30), t(45) and t(105); P<0.05). Furthermore, with GluF, we observed higher levels of lipoperoxides (t(15), t(30), t(45) and t(105); P<0.05) and oxidized LDL (low-density lipoprotein; t(30); P<0.05) compared with after the ingestion of Glu alone. In conclusion, hormonal and lipid alterations are provoked during aerobic exercise and recovery by the addition of a dose of fructose to the pre-exercise ingestion of glucose.