•Fipronil sulfone metabolite was more cytotoxic than fipronil in SH-SY5Y cells.•Fipronil and fipronil sulfone induced NO and MDA production in SH-SY5Y cells.•Antioxidant compounds ameliorated ...fipronil and fipronil sulfone cytotoxicity.
Fipronil is a broad spectrum insecticide from the phenyl pyrazole family, which targets GABA receptor. Limited information is available about the metabolite fipronil sulfone cytotoxic actions. This study examined in vitro neurotoxicity of fipronil and fipronil sulfone and evaluated Trolox (vitamin E analog) (0.3, 1μM), N-acetyl-cysteine (0.5, 1mM), melatonin (0.1, 1μM) and Tempol (superoxide dismutase analog) (0.3, 0.5mM) protective role in SH-SY5Y cells. MTT and LDH assays were carried out to assess the cytotoxicity of fipronil and fipronil sulfone at 3–100μM concentrations. Fipronil sulfone was more toxic than fipronil. Tempol showed the best neuroprotectant profile against fipronil (50 and 150μM) and fipronil sulfone (3 and 10μM) reaching control levels. Fipronil (100μM) and fipronil sulfone (3μM) treatments induced a 4.7- and 5-fold increases in lipid peroxides measured as malondialdehyde (MDA) and a 2.2- and 2.0-fold increases in the levels of nitric oxide (NO). These results suggest that oxidative stress observed may be one of the major mechanisms of fipronil-induced neurotoxicity and it may be attributed in part to fipronil disposition and metabolism. Our results led us postulate that metabolite fipronil sulfone might be responsible for the fipronil-induced toxicity rather than fipronil itself.
The dietary inflammatory index (DII) is a new tool to assess the inflammatory potential of the diet. In the present study, we aimed to determine the association between the DII and BMI, waist ...circumference and waist:height ratio (WHtR). We conducted a cross-sectional study of 7236 participants recruited into the PREvención con DIeta MEDiterránea trial. Information from a validated 137-item FFQ was used to calculate energy, food and nutrient intakes. A fourteen-item dietary screener was used to assess adherence to the Mediterranean diet (MeDiet). Sex-specific multivariable linear regression models were fitted to estimate differences (and 95 % CI) in BMI, waist circumference and WHtR across the quintiles of the DII. All nutrient intakes, healthy foods and adherence to the MeDiet were higher in the quintile with the lowest DII score (more anti-inflammatory values) except for intakes of animal protein, saturated fat and monounsaturated fat. Although an inverse association between the DII and total energy was apparent, the DII was associated with higher average BMI, waist circumference and WHtR after adjusting for known risk factors. The adjusted difference in the WHtR for women and men between the highest and lowest quintiles of the DII was 1·60 % (95 % CI 0·87, 2·33) and 1·04 % (95 % CI 0·35, 1·74), respectively. Pro-inflammatory scores remained associated with obesity after controlling for the effect that adherence to a MeDiet had on inflammation. In conclusion, the present study shows a direct association between the DII and indices of obesity, and supports the hypothesis that diet may have a role in the development of obesity through inflammatory modulation mechanisms.
OBJECTIVE: XXXto assess the effect on cognition of a controlled intervention testing Mediterranean diets (MedDiet). DESIGN: XXXrandomized trial after 6.5 years of nutritional intervention. SETTING: ...Eight primary care centers affiliated to the University of Navarra. PARTICIPANTS: A random subsample of 285 participants (95 randomly allocated to each of 3 groups) of the PREDIMED-NAVARRA trial. All of them were at high vascular risk (44.8% men, 74.1± 5.7 years at cognitive evaluation). INTERVENTIONS: Nutritional intervention comparing two MedDiets (supplemented with extra-virgin olive oil EVOO or mixed nuts) versus a low-fat control diet. Participants received intensive education to increase adherence to the intended intervention. Participants allocated to the MedDiet groups received EVOO (1 l/week) or 30 g/day of mixed nuts. Dietary habits were evaluated using a validated 137-item food frequency questionnaire (FFQ). Additionally, adherence to MedDiet was appraised using a 14-item questionnaire both at baseline and yearly thereafter. MEASUREMENTS: XXXcognitive performance as a main outcome and cognitive status (normal, mild cognitive impairment MCI or dementia) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention. RESULTS: Better post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group. After adjustment for sex, age, education, apolipoprotein E genotype, family history of cognitive impairment/dementia, smoking, physical activity, body mass index, hypertension, dyslipidaemia, diabetes, alcohol and total energy intake, this group also showed lower MCI (OR=0.34 95% CI: 0.12–0.97) compared with control group. Participants assigned to MedDiet+Nuts group did not differ from controls. CONCLUSION: A long-term intervention with an EVOO-rich MedDiet resulted in a better cognitive function in comparison with a control diet. However, non-significant differences were found for most cognitive domains. Participants allocated to an EVOO-rich MedDiet had less MCI than controls.
This report includes the reanalysis of data from a clinical trial showing a lower rate of cardiovascular events among persons assigned to a Mediterranean diet supplemented with extra-virgin olive oil ...or nuts than among those assigned to a low-fat diet.
We studied the effect of silymarin and dimercaptosuccinic acid (DMSA), a chelating agent that was administered individually or in combination against lead (Pb) toxicity in rats. Wistar rats (200 ± ...20) were randomly divided into five groups. Group A served as a control. Groups B–E were exposed to 2000 ppm of lead acetate in drinking water for 8 weeks. Group B served as a positive control. Group C received silymarin (100 mg kg−1 orally) for 8 weeks. Group D received DMSA (75 mg kg−1 orally) once daily for the last 5 days of treatment. Group E received DMSA and silymarin as groups C and D, respectively. The effect of Pb was evaluated and accordingly the treatments on blood lead levels (BLLs), renal system, and genotoxic effects were calculated using comet assay. The BLLs were significantly increased following the exposition of lead acetate. The administration of silymarin and DMSA provided reduction in BLLs. Silymarin and DMSA provided significant protection on the genotoxic effect of Pb. The toxic effect of Pb on kidneys was also studied. Our data suggest that silymarin and DMSA improve the renal histopathological lesions.
We analyze the complete set of in-situ meteorological data obtained from the Viking landers in the 1970s to todays Curiosity rover to review our understanding of the modern near-surface climate of ...Mars, with focus on the dust, CO2 and H2O cycles and their impact on the radiative and thermodynamic conditions near the surface. In particular, we provide values of the highest confidence possible for atmospheric opacity, atmospheric pressure, near-surface air temperature, ground temperature, near-surface wind speed and direction, and near-surface air relative humidity and water vapor content. Then, we study the diurnal, seasonal and interannual variability of these quantities over a span of more than twenty Martian years. Finally, we propose measurements to improve our understanding of the Martian dust and H2O cycles, and discuss the potential for liquid water formation under Mars present day conditions and its implications for future Mars missions.
The toxicokinetics of glyphosate after single 100
mg
kg
−1 intravenous (i.v.) and 400
mg
kg
−1 oral doses were studied in rats. Serial blood samples were obtained after i.v. and oral administration. ...Plasma concentrations of glyphosate and its metabolite amiomethyl phosphonic acid (AMPA) were determined by HPLC method. After i.v. and oral administration, plasma concentration–time curves were best described by a two-compartment open model. For glyphosate, the elimination half-lives (
T
1/2β) from plasma were 9.99
h after i.v. and 14.38
h after oral administration. The total plasma clearance was not influenced by dose concentration or route and reached a value of 0.995
l
h
−1
kg
−1. After i.v. administration, the apparent volume of distribution in the second compartment (
V
2) and volume of distribution at steady state (
V
ss) were 2.39 and 2.99
l
kg
−1, respectively, suggesting a considerable diffusion of the herbicide into tissues. After oral administration, glyphosate was partially and slowly absorbed with a
T
max of 5.16
h. The oral bioavailability of glyphosate was found to be 23.21%. Glyphosate was converted to AMPA. The metabolite AMPA represented 6.49% of the parent drug plasma concentrations. The maximum plasma concentrations of glyphosate and AMPA were 4.62 and 0.416
μg
ml
−1, respectively. The maximum plasma concentration of AMPA was achieved at 2.42
h. For AMPA, the elimination half-life (
T
1/2β) was 15.08
h after oral administration of glyphosate parent compound.
The influence of home cooking methods (boiling, microwaving, pressure-cooking, griddling, frying, and baking) on the antioxidant activity of vegetables has been evaluated in 20 vegetables, using ...different antioxidant activity assays (lipoperoxyl and hydroxyl radicals scavenging and TEAC). Artichoke was the only vegetable that kept its very high scavenging-lipoperoxyl radical capacity in all the cooking methods. The highest losses of LOO· scavenging capacity were observed in cauliflower after boiling and microwaving, pea after boiling, and zucchini after boiling and frying. Beetroot, green bean, and garlic kept their antioxidant activity after most cooking treatments. Swiss chard and pepper lost OH· scavenging capacity in all the processes. Celery increased its antioxidant capacity in all the cooking methods, except boiling when it lost 14%. Analysis of the ABTS radical scavenging capacity of the different vegetables showed that the highest losses occurred in garlic with all the methods, except microwaving. Among the vegetables that increased their TEAC values were green bean, celery, and carrot after all cooking methods (except green bean after boiling). These 3 types of vegetables showed a low ABTS radical scavenging capacity. ccording to the method of analysis chosen, griddling, microwave cooking, and baking alternately produce the lowest losses, while pressure-cooking and boiling lead to the greatest losses; frying occupies an intermediate position. In short, water is not the cook's best friend when it comes to preparing vegetables.
Abstract Background and aim The Mediterranean diet is considered a model for healthy eating. However, prospective evidence in Mediterranean countries evaluating the relationship between this dietary ...pattern and non-fatal cardiovascular events is scarce. The aim of the present study was to evaluate the association between the adherence to the Mediterranean diet and the incidence of fatal and non-fatal cardiovascular events among initially healthy middle-aged adults from the Mediterranean area. Methods and results We followed-up 13,609 participants (60 percent women, mean age: 38 years) initially free of cardiovascular disease (CVD) during 4.9 years. Participants were part of a prospective cohort study of university graduates from all regions of Spain. Baseline diet was assessed using a validated 136-item food-frequency questionnaire. A 9-point score was used to appraise adherence to the Mediterranean diet. Incident clinical events were confirmed by a review of medical records. We observed 100 incident cases of CVD. In multivariate analyses, participants with the highest adherence to the Mediterranean diet (score > 6) exhibited a lower cardiovascular risk (hazard ratio = 0.41, 95% confidence interval CI: 0.18–0.95) compared to those with the lowest score (<3). For each 2-point increment in the score, the adjusted hazard ratios were 0.80 (95% CI: 0.62–1.02) for total CVD and 0.74 (0.55–0.99) for coronary heart disease. Conclusions There is an inverse association between adherence to the Mediterranean diet and the incidence of fatal and non-fatal CVD in initially healthy middle-aged adults.
Telomeres are nucleoprotein structures that protect the ends of eukaryote chromosomes. Shorter telomere length (TL) is associated with some age-related human disorders, but its relationship with ...obesity or adiposity parameters remains unclear.
The aim of this study was to assess the relationship between TL and changes in adiposity indices after a 5-year nutritional intervention.
TL was measured by quantitative real-time PCR in 521 subjects (55-80 years, 55% women). Participants were randomly selected from the PREDIMED-NAVARRA centre after they completed a 5-year intervention programme. Anthropometric parameters were directly measured by trained personnel at baseline and on a yearly basis thereafter. TL at baseline and changes in TL after a 5-year intervention were assessed.
Higher baseline TL significantly predicted a greater decrease in body weight (B=-1.09 kg, 95% confidence interval (CI): -2.01 to -0.16), body mass index (BMI) (B=-0.47 kg m(-2), 95% CI: -0.83 to -0.11), waist circumference (B=-1.15 cm, 95% CI: -2.28 to -0.01) and waist to height ratio (B=-0.008, 95% CI: -0.010 to -0.001) in multiple-adjusted models. In addition, changes in TL during the 5-year intervention were inversely associated with changes in the four anthropometric variables. The reduction in adiposity indices during the intervention, associated with increasing TL, was even higher among subjects with the longest telomeres at baseline. Logistic regression analysis showed that the risk of remaining obese after 5 years was lower in those participants who initially had the longest telomeres and increased their TL after intervention (odds ratio=0.27, 95% CI: 0.03-2.03).
Our research suggests that TL is inversely associated with changes in obesity parameters. The assessment of TL can provide further insights for biological pathways leading to adiposity. We show for the first time an improvement of obesity indices when an increase in TL is observed after a 5-year Mediterranean diet intervention.
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