Evaluation of redox profiles in exogenous subclinical hyperthyroidism at two different levels of TSH suppression.

OBJECTIVE: Evaluate the relationship between exogenous subclinical hyperthyroidism and oxidative stress through the analysis of the redox profile of patients with subclinical hyperthyroidism exogenous (SCH) grade I (TSH = 0.1 to 0.4 IU/mL) and grade II (TSH < 0.1 IU/mL). SUBJECTS AND METHODS: We analyzed 46 patients with SCH due to the use of TSH suppressive therapy with LT4 after total thyroidectomy along with 6 control euthyroid individuals (3M and 3W). Patients were divided into two groups, G1 with TSH ≥ 0.1-0.4 IU/mL (n = 25; and 7M 14W) and G2 with TSH < 0.1 IU/mL (n = 25; and 4M 21W). Venous blood samples were collected to measure the levels of markers for oxidative damage (TBARS, FOX and protein carbonylation), muscle and liver damage (CK, AST, ALT, GGT) and antioxidants (GSH, GSSG and catalase). RESULTS: Individuals in G2 showed a GSH/GSSG ratio ~ 30% greater than those in G1 (p = 0.004) and a catalase activity that was 4 times higher (p = 0.005). For lipid peroxidation, the levels measured in G2 were higher than both control and G1 (p = 0.05). No differences were observed for both protein carbonyl markers. G1 and G2 presented with greater indications of cell injury markers than the control group. CONCLUSION: TSH suppression therapy with LT4 that results in subclinical hyperthyroidism can cause a redox imbalance. The greater antioxidant capacity observed in the more suppressed group was not sufficient to avoid lipid peroxidation and cellular damage.

Evaluation of redox profiles in exogenous subclinical hyperthyroidism at two different levels of TSH suppression

ABSTRACT Objective: Evaluate the relationship between exogenous subclinical hyperthyroidism and oxidative stress through the analysis of the redox profile of patients with subclinical hyperthyroidism exogenous (SCH) grade I (TSH = 0.1 to 0.4 IU/mL) and grade II (TSH < 0.1 IU/mL). Subjects and methods: We analyzed 46 patients with SCH due to the use of TSH suppressive therapy with LT4 after total thyroidectomy along with 6 control euthyroid individuals (3M and 3W). Patients were divided into two groups, G1 with TSH ≥ 0.1-0.4 IU/mL (n = 25; and 7M 14W) and G2 with TSH < 0.1 IU/mL (n = 25; and 4M 21W). Venous blood samples were collected to measure the levels of markers for oxidative damage (TBARS, FOX and protein carbonylation), muscle and liver damage (CK, AST, ALT, GGT) and antioxidants (GSH, GSSG and catalase). Results: Individuals in G2 showed a GSH/GSSG ratio ~ 30% greater than those in G1 (p = 0.004) and a catalase activity that was 4 times higher (p = 0.005). For lipid peroxidation, the levels measured in G2 were higher than both control and G1 (p = 0.05). No differences were observed for both protein carbonyl markers. G1 and G2 presented with greater indications of cell injury markers than the control group. Conclusion: TSH suppression therapy with LT4 that results in subclinical hyperthyroidism can cause a redox imbalance. The greater antioxidant capacity observed in the more suppressed group was not sufficient to avoid lipid peroxidation and cellular damage.

Phenolic metabolites in plasma and tissues of rats fed with a grape pomace extract as assessed by liquid chromatography-tandem mass spectrometry.

Grape pomace extract (GPE) is a rich and relatively low-cost source of phenolic compounds. However, little is known about the main GPE metabolites in mammals, which could help explain the observed health-promoting effects. This study investigated the presence of parent compounds from flavanol, flavonol and stilbene families and their metabolites in rat plasma and tissues after an acute intake of GPE in doses of 300 and 600 mg kg/body weight. The measurement of free compounds and their metabolites was performed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Results showed the presence of epicatechin, epicatechin methyl-glucuronide, epicatechin methyl-sulphate, catechin, catechin-glucuronide, quercetin methyl-glucuronide, resveratrol-3-glucuronide, resveratrol-4-glucuronide and resveratrol-3-sulphate in plasma, which was dose dependent. The most abundant measured compound in plasma was epicatechin-glucuronide. The presence of glucuronidated and methyl-glucuronidated forms of catechin were observed in the liver at both doses, while epicatechin-glucuronide and methyl-glucuronide were detected only upon intake of 600 mg GPE/kg body weight. At this dose epicatechin-glucuronide and methyl-glucuronide were also detected in muscle, and catechin methyl-glucuronide in adipose tissue. Results show the main GPE metabolites present in rat tissues after oral consumption, contributing to better understand the health benefits of GPE and its potential utilization as a functional ingredient.

Processing 'Ataulfo' Mango into Juice Preserves the Bioavailability and Antioxidant Capacity of Its Phenolic Compounds.

The health-promoting effects of phenolic compounds depend on their bioaccessibility from the food matrix and their consequent bioavailability. We carried out a randomized crossover pilot clinical trial to evaluate the matrix effect (raw flesh and juice) of 'Ataulfo' mango on the bioavailability of its phenolic compounds. Twelve healthy male subjects consumed a dose of mango flesh or juice. Blood was collected for six hours after consumption, and urine for 24 h. Plasma and urine phenolics were analyzed by electrochemical detection coupled to high performance liquid chromatography (HPLC-ECD). Five compounds were identified and quantified in plasma. Six phenolic compounds, plus a microbial metabolite (pyrogallol) were quantified in urine, suggesting colonic metabolism. The maximum plasma concentration (Cmax) occurred 2-4 h after consumption; excretion rates were maximum at 8-24 h. Mango flesh contributed to greater protocatechuic acid absorption (49%), mango juice contributed to higher chlorogenic acid absorption (62%). Our data suggests that the bioavailability and antioxidant capacity of mango phenolics is preserved, and may be increased when the flesh is processed into juice.

Effects of mate tea consumption on muscle strength and oxidative stress markers after eccentric exercise.

Dietary phytochemical supplementation may improve muscle recovery from exercise. In this study, we investigated the effect of mate tea (MT) consumption - a phenol-rich beverage - on muscle strength and oxidative stress biomarkers after eccentric exercise. In a randomised, cross-over design, twelve men were assigned to drink either MT or water (control; CON) for 11 d. On the 8th day, subjects performed three sets of twenty maximal eccentric elbow flexion exercises. Maximal isometric elbow flexion force was measured before and at 0, 24, 48 and 72 h after exercise. Blood samples were obtained before and at 24, 48 and 72 h after exercise and analysed for total phenolics, GSH, GSSG, GSH:GSSG ratio and lipid hydroperoxides (LOOH). After eccentric exercise, muscle strength was significantly reduced over time, regardless of treatments. However, MT improved the rate of strength recovery by 8·6 % on the 1st day after exercise (P<0·05). Plasma concentration of total phenolic compounds was higher in MT than in CON at all time points (P<0·05) but decreased significantly at 72 h after exercise in both trials (P<0·05). Blood levels of GSH were significantly decreased at 48 and 72 h after exercise in CON (P<0·05) but did not change over time in MT. No significant changes were observed for GSSG, GSH:GSSG ratio and LOOH levels. MT intake did not influence muscle strength at all time points assessed but hastened the strength recovery over 24 h after exercise. MT also favoured the concentration of blood antioxidant compounds.

Novel natural food colourant G8000 benefits LDL- and HDL-cholesterol in humans.

The aim of this study was to investigate the phenolic composition of a natural food colourant (G8000™) as well as its effects on plasma markers after 28-day consumption by healthy individuals at a dietary dose (70 g). Parameters of total cholesterol and its fractions, triglycerides and plasma enzymes biomarkers of muscle injury were measured. Major compounds identified in G8000™ by ESI-MS showed the presence of anthocyanins, organic acids, phenolic acids as well as monosaccharides. HDL levels significantly increased from 43 ± 10.2 mg/dL to 95 ± 16.9 mg/dL. LDL levels significantly decreased from 110 ± 40.9 mg/dL to 69 ± 39 mg/dL (p < 0.001). No significant statistical differences (p > 0.05) were observed for total cholesterol, triglycerides and VLDL. After the intake, plasma enzyme CK-MB decreased from 20 ± 12.1 U/L to 10 ± 1.9 U/L while LDH levels increased from 275 ± 124.4 U/L to 317 ± 114.7 U/L (p < 0.005). No significant differences were observed for CK levels. Taken together, dietary intake of natural colourant G8000™ was able to exert beneficial effects on atherosclerosis biomarkers.

Case report of a fatal intoxication by Nucynta.

Tapentadol (Nucynta) is a centrally acting opioid analgesic prescribed for the treatment of moderate to severe acute pain. Its efficacy is believed to be due to µ-opioid receptor agonist activity and inhibition of norepinephrine reuptake resulting in increased norepinephrine concentrations. There is only one other case in the literature relating to the toxicity of this agent or report of a fatality. This case report documents a case in which tapentadol was identified as the cause of death. The tapentadol concentration found in the heart blood submitted in this case was more than 20 times the upper limit of the therapeutic range. Possible mechanisms of death include respiratory depression, central nervous system depression, and serotonin syndrome. Based on the scene investigation and autopsy findings in this case, the medical examiner determined that the cause of death was narcotic (Nucynta) intoxication and the manner of death was undetermined.

Evaluation of blood Bisphenol A contents: a case study / Evaluación de las concentraciones de Bisfenol A en la sangre: estudio de caso

OBJECTIVE: It has been recently reported that Bisphenol A (BPA) may leach out into food, beverages and water samples from the plastic ware in which it is stored. Serious health hazards have been reported from BPA. The purpose of this study is to assess the BPA contents in blood and to assess the risk of cancer. METHOD: A total of 100 individuals were selected for study according to the following five age groups: 5-10, 11-20, 21-30, 31-40 and 41-50 years. They were then further divided into normal and diseased. Age, gender, education, source of drinking water, type of food, smoking habit, any exposure to chemicals and history of cancer were elicited during interview. Blood samples were collected and processed for analysis using reversed phase-high performance liquid chromatography (rp-HPLC) in isocratic mode. The mobile phase consisted of acetonitrile and water (1:1) at a flow-rate of 1 ml min-1. RESULTS: Bisphenol A contents found in blood samples of all age groups ranged from 1.53-3.98 (mean = 2.94, SD = 0.9). P-values, for the exposed people and those having a history of cancer, were < 0.05 showing a significant relationship between BPA and cancer. The United States Environmental Protection Agency (US EPA) has established a reference dose of 50 µg/L. Odd ratios and relative risk for smoking habit were < 1 while for all others they were > 1. CONCLUSION: It was concluded from the study that people using bottled water, packaged food, having a history ofcancer and who had been exposed to any type ofchemicals are at higher risk ofdisease.

OBJETIVO: Se ha reportado recientemente que el bisfenol A (BPA) puede filtrarse a alimentos, bebidas y agua, a partir de los recipientes plásticos en que aquellos se almacenan. En tal sentido, se han reportado serios casos de riesgo para la salud a causa del BPA. El propósito de este estudio es evaluar la concentración de BPA en sangre, y el consiguiente riesgo de enfermedades cancerosas. MÉTODO: Un total de 100 individuos fueron seleccionados para el estudio, de acuerdo con los siguientes cinco grupos etarios: 5-10, 11-20, 21-30, 31-40 y 41-50 años. Dichos grupos fueron divididos entonces sobre la base de sujetos normales frente a enfermos. En la entrevista se tomó nota de la edad, el género, la educación, la fuente de agua potable, el tipo de comida, el hábito de fumar, cualquier exposición a productos químicos, así como la historia de cáncer. Las muestras de sangre fueron recogidas y procesadas para realizar análisis, utilizando cromatografía líquida de alta eficacia de fase reversa (rp-HPLC) en modo isocrático. La fase móvil consistió en acetonitrilo y agua (1:1) con una tasa de flujo de 1 ml min-1. RESULTADOS: Las concentraciones de bisfenol-A halladas en las muestras de sangre de todos los grupos etarios, oscilaron de 1.53 - 3.98 (M = 2.94, SD = 0.9). Los valores P para las personas expuestas y con una historia de cáncer, fueron < 0.05, indicando una relación directa entre el BPA y el cáncer. La Agencia de Protección Ambiental de los Estados Unidos (US EPA) ha establecido una dosis de referencia de 50 µg/L. El cociente de probabilidades (odd ratios) y el riesgo relativo con respecto al hábito de fumar fueron < 1 mientras que para todos los otros casos otros fueron >1. CONCLUSIÓN: A partir del estudio se concluye que las personas que usan agua embotellada, alimentos empaquetados, así como las personas que poseen una historia de cáncer, y los individuos que habían estado expuestos a cualquier tipo de productos químicos, presentan un mayor riesgo de enfermedad.

Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A / Estudos de biomonitoração do sistema urinário, circulatório e tecidos indicam grande exposição ao Bisfenol A

Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. We examined many possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. More than 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism were examined. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes.

Bisfenol A (BPA) é um dos produtos químicos mais produzido em todo o mundo, e a exposição humana a ele é considerada onipresente. Assim, há preocupações de que a quantidade de BPA para o qual os seres humanos estão expostos podem causar efeitos adversos à saúde. Nós examinamos muitas possibilidades sobre o porquê estudos de biomonitorização e toxicocinética podem chegar a conclusões aparentemente conflitantes. Mais de 80 estudos publicados de biomonitorização humana que mediram a concentração de BPA em tecidos humanos, urina, sangue e outros fluidos, juntamente com dois estudos de toxicocinética do metabolismo humano BPA foram examinados. BPA não conjugado foi detectado no sangue (nonanogramas por mililitro gama), e BPA conjugado foi detectado na grande maioria das amostras de urina. Em contraste, estudos de toxico-cinética propuseram que os seres humanos não são internamente expostos ao BPA. Dados disponíveis de estudos de biomonitorização indicam que a população em geral está exposta ao BPA e em risco de exposição interna ao BPA não conjugado. Os dois estudos de toxicocinética, que sugeriram a exposição humana ao BPA é insignificante, têm deficiências significativas e estão diretamente refutados por outros estudos e, portanto não são confiáveis para fins de avaliação de risco.

Antioxidant biomarkers and food intake in elderly women.

OBJECTIVE: To investigate the relationship between antioxidant biomarkers and food intake in elderly women. DESIGN: Cross-sectional study. SETTING: Recreation Center for the Elderly in the city of Itajaí, Santa Catarina, Brazil. PARTICIPANTS: 73 elderly women with an average age of 71 years, 93% caucasian, average body weight 68.7 ± 13.1 kg and average BMI 28.5 ± 2.3 kg/m². MEASUREMENTS: Nutritional status was assessed based on the Body Mass Index (BMI). Data on food intake were obtained by applying the 24h diet recall method in three non-consecutive days, including Sunday. The assessment of antioxidant biomarkers was performed based on tests for total plasma thiols and phenolic compounds. The linear regression analysis was used to assess the effect of the consumption of food groups on antioxidant biomarkers. RESULTS: A positive association was found between thiols and intake of carotenoid-rich vegetables (p=0.03), oils, fats and oilseeds (p=0.03); a negative association was observed between total concentrations of phenolic compounds and intake of cereals (p=0.04). CONCLUSION: The intake of foods from the carotenoid-rich vegetables, oils, fats and oilseeds food groups increased the levels of plasma thiols, and the intake of foods from the group of cereals decreased the plasma concentration of phenols. Studies should be conducted to investigate the association between the intake of antioxidant-rich foods and the plasma antioxidant profile, as a way to protect against the aging process.

Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A.

Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. We examined many possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. More than 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism were examined. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes.

Evaluation of blood bisphenol A contents: a case study.

OBJECTIVE: It has been recently reported that Bisphenol A (BPA) may leach out into food, beverages and water samples from the plastic ware in which it is stored. Serious health hazards have been reported from BPA. The purpose of this study is to assess the BPA contents in blood and to assess the risk of cancer. METHOD: A total of 100 individuals were selected for study according to the following five age groups: 5-10, 11-20, 21-30, 31-40 and 41-50 years. They were then further divided into normal and diseased. Age, gender, education, source of drinking water, type of food, smoking habit, any exposure to chemicals and history of cancer were elicited during interview. Blood samples were collected and processed for analysis using reversed phase-high performance liquid chromatography (rp-HPLC) in isocratic mode. The mobile phase consisted of acetonitrile and water (1:1) at a flow-rate of 1 ml min-1. RESULTS: Bisphenol A contents found in blood samples of all age groups ranged from 1.53-3.98 (mean = 2.94, SD = 0.9). P-values, for the exposed people and those having a history of cancer, were < 0.05 showing a significant relationship between BPA and cancer The United States Environmental Protection Agency (US EPA) has established a reference dose of 50 microg/L. Odd ratios and relative risk for smoking habit were < 1 while for all others they were > 1. CONCLUSION: It was concluded from the study that people using bottled water, packaged food, having a history of cancer and who had been exposed to any type of chemicals are at higher risk of disease.

Wine, diet, antioxidant defenses, and oxidative damage.

Oxidative stress is a central mechanism for the pathogenesis of ischemic heart disease and atherogenesis, for cancer and other chronic diseases in general, and it also plays a major role in the aging process. Dietary antioxidants constitute a large group of compounds that differ in mechanism of action, bioavailability and side effects. A systematic analysis of the role of the various antioxidants in chronic diseases is hampered by the difficulty of employing death or clinical events as end points in intervention studies. Therefore, valid markers for oxidative stress, which show dose response and are sensitive to changes in dietary supply of antioxidants, are potentially of great value when trying to establish healthy dietary patterns, or when one component, like red wine, is evaluated specifically. To evaluate potential oxidative stress markers we have studied the effect of different diets plus wine supplementation on antioxidant defenses and oxidative damage. In three experimental series, four groups of young male university students, one of older men and other of older women, 20-24 volunteers each, received Mediterranean or occidental (high-fat) diets alone or supplemented with red wine, white wine, or fruits and vegetables. Measurements included, leukocyte DNA 8-OH-deoxyguanosine (8OHdG), plasma 7 beta-hydroxycholesterol, TBARS and well-characterized antioxidants, and plasma and urine polyphenol antioxidants. In all experimental groups that received red wine, consumption resulted in marked decrease in 8OHdG. The changes observed in 8OHdG correlate positively with the other markers of oxidative damage, and shows a clear inverse correlation with the plasma level of well established antioxidants and with measurements of total antioxidant capacity. Urinary total polyphenol content as well as the sum of some specific plasma species also correlate inversely with 8OHdG. In conclusion, the results identify 8OHdG as a very promising general marker of oxidative stress in nutrition intervention studies in humans, and red wine shows a remarkable protective effect.

Modulation of rat liver cytochrome P450 activity by prolonged red wine consumption.

Cytochrome P450-dependent oxidation of lauric acid, p-nitrophenol and ethanol by liver microsomal fractions were studied in control rats and in animals given either ethanol, red wine, or alcohol-free red wine for 10 weeks. Ethanol increased the total cytochrome P450 and the isoenzyme 2E1 content, as well as the p-nitrophenol hydroxylation and ethanol oxidation. These effects of ethanol treatment were attenuated by red wine administration. Red wine increased the total antioxidant capacity of plasma, whereas the alcohol-free red wine decreased the cytochrome P450 content and decreased the oxidation of lauric acid, p-nitrophenol and ethanol to values lower than control. It is concluded that red wine administration attenuates the ethanol-induced enhancement in liver microsomal parameters dependent on cytochrome P450 2E1 activity, an affect that seems to be accomplished by the non-alcoholic constituents of red wine known to have antioxidant properties.

Plasma polyphenols and antioxidants, oxidative DNA damage and endothelial function in a diet and wine intervention study in humans.

An intervention study was performed to evaluate the influence of a Mediterranean diet, a high fat diet, and their supplementation with red wine in moderate amounts, on biochemical, physiological, and clinical parameters related to atherosclerosis and other chronic diseases. For 3 months two groups of 21 male volunteers each, received either a Mediterranean diet or a high fat diet; during the second month, red wine was added isocalorically, 240 ml/day. Participants were kept under close medical and nutritional surveillance. At days 0, 30, 60 and 90, clinical, physiological and biochemical evaluations were made. Plasma vitamin C was significantly decreased in the high fat diet group compared to the Mediterranean diet group. After wine supplementation to the Mediterranean diet, a significant 13.5% increase in plasma vitamin C was observed. Furthermore, when wine was added vitamin E decreased significantly in plasma, 15% in the high fat diet and 26% in the Mediterranean diet. Total plasma antioxidant capacity (total antioxidant reactivity) increased 28% above basal levels in the Mediterranean diet group, but not in the high fat diet group. In both groups, wine induced a marked increase in total antioxidant reactivity above basal levels, 56% and 23%, respectively. Oxidative DNA damage, detected as 8-hydroxydeoxyguanosine (8-OHdG) levels in blood leukocyte DNA, was markedly increased by the high fat diet; however, it was strongly reduced, to approximately 50% basal values, after wine supplementation, both in the high fat diet and Mediterranean diet groups. Endothelial function, evaluated noninvasively as flow-mediated vascular reactivity of the brachial artery, was suppressed by the high fat diet, and was normal after wine supplementation. These effects are attributed to oxidative stress associated with a high fat diet, and to the elevated plasma antioxidant capacity associated with wine consumption and the Mediterranean diet. The results presented support the following conclusions: a high fat diet induces oxidative stress; a diet rich in fruits and vegetables enhances antioxidant defenses; wine supplementation to a high fat or a Mediterranean diet increases plasma antioxidant capacity, decreases oxidative DNA damage, and normalizes endothelial function.