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The high consumption of dietary supplements was a fundamental driver for the creation of the regulatory framework by the Brazilian governmental authorities. However, the regulatory agencies lack official low-cost methodologies to evaluate the quality of food supplements. A preliminary screening method by HPLC-DAD was proposed and validated for screening and quantification of adulterants in dietary supplements. The limits of detection and quantification were <0.11 and 0.37 µg.g-1, respectively. The method was applied for the investigation of ten unauthorized substances (spironolactone, hydrochlorothiazide, furosemide, clenbuterol, testosterone, testosterone propionate, yohimbine, vardenafil, tadalafil, and sildenafil) with a time of analysis of <5 min. Sixteen percent of the 44 samples analyzed had at least one adulterant at or above therapeutic concentrations. Subsequently, in vitro evaluations were performed of the potential cytotoxicity to evaluate the cell viability, DNA damage, determination of nitric oxide levels, and quantification of reactive oxygen species. Despite the necessity of further studies, the results indicate a relationship between the presence of adulterants in food supplements and a potential cytotoxic effect.

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Dietary supplements are drastically growing as a category of consumer products all over the world. The abuse of supplements marketed for slimming purposes and physical fitness has been observed worldwide in recent years, which raises concerns in terms of public health. In this study, different types of dietary supplements marketed and delivered through the e-commerce were studied for the determination of thallium as a hazardous inorganic contaminant. The total content of thallium was determined by a sensitive voltammetric method after a microwave-assisted oxidative digestion of the sample. In addition, a comparative spectrometric method was applied for validation of the results in the samples. The maximum concentration found for thallium was found to be 2.89 mg kg-1, which well agree with the comparative measurement. Considering the 32 studied formulations, it can be pointed out that ∼24% of the of dietary supplements presented Tl concentrations at concentrations higher than 1 mg kg-1. The results permitted the assessment of the health risk related to thallium from contaminated samples, based on the calculation of the estimated daily intake (EDI) and the risk quotient (HQ). The highest daily intake of thallium was calculated as 82.0 µg day-1 in a protein-based supplement, which is equivalent to an EDI of 1.17 µg kg-1 day-1. This work highlights the need to develop regulations on the limits of toxic elements such as thallium in widely consumed dietary supplements, as well as an in-depth look at the adverse effects caused by this element in the human body.

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Females are born with a finite number of oocyte-containing follicles and ovary damage results in reduced fertility. Cadmium accumulates in the reproductive system, damaging it, and the cigarette smoke is a potential exposure route. Natural therapies are relevant to health benefits and disease prevention. This study verified the effect of cadmium exposure on the ovaries of mice and the blueberry extract as a potential therapy. Blueberry therapy was effective in restoring reactive species levels and δ-aminolevulinate dehydratase activity, and partially improved the viability of cadmium-disrupted follicles. This therapy was not able to restore the 17 ß-hydroxysteroid dehydrogenase activity. Extract HPLC evaluation indicated the presence of quercetin, quercitrin, isoquercetin, and ascorbic acid. Ascorbic acid was the major substance and its concentration was 620.24 µg/mL. Thus, cadmium accumulates in the ovaries of mice after subchronic exposure, inducing cellular damage, and the blueberry extract possesses antioxidant properties that could protect, at least in part, the ovarian tissue from cadmium toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 188-196, 2017.

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Aluminum (Al) is the most widely distributed metal in the environment and is extensively used in daily life leading to easy exposure to human beings. Besides not having a recognized physiological role, Al may produce adverse effects through the interaction with the cholinergic system contributing to oxidative stress. The present study evaluated, in similar conditions of parenteral nutrition, whether the reaction of silicon (SiO2) with Al(3+) to form hydroxyaluminosilicates (HAS) reduces its bioavailability and toxicity through intraperitoneal administrations of 0.5 mg Al/kg/day and/or 2 mg Si/kg/day in Wistar rats. Al and Si concentrations were determined in rat brain tissue and serum. Acetylcholinesterase (AChE) activity and lipid peroxidation (LPO) were analyzed in the cerebellum, cortex, hippocampus, striatum, hypothalamus, and blood. An increase in the Al concentration was verified in the Al + Si group in the brain. All the groups demonstrated enhanced Si compared to the control animals. Al(3+) increased LPO measured by thiobarbituric acid reactive substances (TBARS) in cerebellum and hippocampus, whereas SiO2 reduced it when compared with the control group. An increase of AChE activity was observed in the Al-treated group in the cerebellum whereas a decrease of this enzyme activity was observed in the cortex and hippocampus in the Al and Al + Si groups. Al and Si concentrations increased in rat serum; however, no effect was observed in blood TBARS levels and AChE activity. SiO2 showed a protective effect in the hippocampus and cerebellum against cellular damage caused by Al(3+)-induced lipid peroxidation. Thus, SiO2 may be considered an important protector in LPO induced by Al(3+).

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Organochalcogens are promising pharmacological agents that possess significant biological activities. Nevertheless, because of the complexity of mammalian models, it has been difficult to determine the molecular pathways and specific proteins that are modulated in response to treatments with these compounds. The nematode worm Caenorhabditis elegans is an alternative experimental model that affords easy genetic manipulations, green fluorescent protein tagging and in vivo live analysis of toxicity. Abundant evidence points to oxidative stress in mediating manganese (Mn)-induced toxicity. In this study we challenged worms with Mn, and investigated the efficacy of inedited selenium- and tellurium-xylofuranosides in reversing and/or protecting the worms from Mn-induced toxicity. In addition, we investigated their putative mechanism of action. First, we determined the lethal dose 50% (LD50) and the effects of the xylofuranosides on various toxic parameters. This was followed by studies on the ability of xylofuranosides to afford protection against Mn-induced toxicity. Both Se- and Te-xylofuranosides increased the expression of superoxide dismutase (SOD-3). Furthermore, we observed that the xylofuranosides induced nuclear translocation of the transcription factor DAF-16/FOXO, which in the worm is known to regulate stress responsiveness, aging and metabolism. These findings suggest that xylofuranosides attenuate toxicity Mn-induced, by regulating the DAF-16/FOXO signaling pathway.

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BACKGROUND: Erythropoietin (EPO) formulations may comprise aluminum (Al) as a contaminant. Due to the toxicity of Al in chronic kidney disease patients, possible sources of Al were investigated. Since EPO formulations are stored in container-closure systems made of glass and rubber, and both contain Al, formulation ingredients may enable its leaching into the solution during shelf-life. METHODS: Individual solutions of formulation ingredients were stored in new glass vials and in contact with the rubber stopper and kept at 4 ± 2 °C. For 12 months, aliquots of each solution were collected for analysis. Fifteen commercial samples of EPO were analyzed for their Al content. Aluminum was determined by atomic absorption spectrometry. RESULTS: Glass and rubber are sources of Al for EPO formulations. Storage assay showed that citrate and phosphate (used as buffers) extracted high amounts of Al from the container/closure parts. The most important difference, however, was found when comparing liquid and lyophilized samples. While in liquid forms the Al level reached 943 µg/L, in lyophilized forms the level did not exceed 20 µg/L. The container system was also confirmed as a source of Al in reconstituted lyophilized samples. Al in reconstituted samples stored in their own vials increased 19-fold in 12 months. Lyophilized powders stored for 2 years in glass vials contained less Al than in 1 month after dissolution. CONCLUSION: The difference in the Al measured in liquid forms of EPO and in lyophilized powders suggests that the latter would be the best pharmaceutical form for CKD patients.

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Erythropoietin (EPO) is a glycoprotein that stimulates erythropoiesis and is clinically used for treating anemia during chronic renal failure and for anemia in preterm infants. EPO formulations usually have elevated rates of contamination due to aluminum (Al), which is toxic to both types of patients. Size-exclusion chromatography (SEC) coupled with graphite furnace atomic absorption spectrometry (GF AAS) was employed to separate proteins and to quantify the amount of aluminum present in the elution volume corresponding to EPO and, therefore, to evaluate possible binding. Because EPO formulations contain human serum albumin (HSA), a chromatographic method was optimized for the separation of these proteins. Subsequent to the chromatographic separation, 1-mL fractions of the column effluent were collected, and the Al content in these aliquots was measured by GF AAS. EPO and HSA samples were incubated with Al for 4h at 4°C and 37°C as well as for 16 h at 4°C and 37°C. Afterwards, they were injected into the chromatographic system. These samples were also submitted to ultrafiltration (10 and 50 kDa membranes), and Al was measured in the ultrafiltrates. The results showed that Al was present in the eluent volume corresponding to the EPO peak but not in the HSA peak in the chromatograms. Temperature strengthened the interaction because the Al present in the EPO fraction was 3 times higher at 37°C compared to 4°C. Thirty-eight percent of the Al present in a 2.4 µg/mL EPO standard solution, and approximately 50% of the Al in formulation samples containing approximately 11 µg/mL EPO and either citrate or phosphate, were non-ultrafiltrable, which suggests that EPO is an effective Al acceptor in vitro.

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BACKGROUND: Aluminum loading can reach toxic levels depending on the amount of aluminum intake in intravenous solutions (IV). Premature infants are at a higher risk of aluminum toxicity because of their reduced urinary aluminum elimination. All steps involved in the preparation of intravenous solutions for premature neonates in intensive care units were evaluated to determine to what degree, if any, they increased the aluminum load and should be considered when assessing the daily aluminum intake (<5 mcg/kg) established by the U.S. Food and Drug Administration (FDA). METHODS: Products and medical devices used for the IV administration of solutions to preterm neonates were analyzed for their aluminum content. Commercial formulations, bags after compounding, and medications before and after their preparation, as well as infusion sets (including burettes) and syringes, were evaluated for their contribution to the aluminum levels in the final solution. The determination was carried out by atomic absorption spectrometry. RESULTS: Currently available products used to prepare parenteral nutrition solutions as well as injectable medications usually administered to premature neonates present aluminum contamination. Bags, burettes, and syringes were also contaminated by aluminum to some degree, which may be leached during use. CONCLUSIONS: Commercial products are the main source of aluminum in parenteral nutrition; nevertheless, manipulation, containers, and administration sets increased aluminum levels by about 40%. Because this is a significant rate, these sources should be taken into account when calculating the amount of aluminum delivered to the patient in order to comply with FDA standards.

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Manganese (Mn) is a metal required by biological systems. However, environmental or occupational exposure to high levels of Mn can produce a neurological disorder called manganism, which has similarities to Parkinson's disease. Diethyl-2-phenyl-2-tellurophenyl vinylphosphonate (DPTVP) is an organotellurium compound with a high antioxidant activity, especially in the brain. The present study was designed to investigate the effects of long-term low-dose exposure to Mn in drinking water on behavioral and biochemical parameters in rats and to determine the effectiveness of vinylic telluride in attenuating the effects of Mn. After 4 months of treatment with MnCl(2) (13.7 mg/kg), rats exhibited clear signs of neurobehavioral toxicity, including a decrease in the number of rearings in the open field and altered motor performance in rotarod. The administration of DPTVP (0.150 micromol/kg, ip, 2 weeks) improved the motor performance of Mn-treated rats, indicating that the compound could be reverting Mn neurotoxicity. Ex vivo, we observed that Mn concentrations in the Mn-treated group were highest in the striatum, consistent with a statistically significant decrease in mitochondrial viability and [(3)H]glutamate uptake, and increased lipid peroxidation. Mn levels in the hippocampus and cortex were indistinguishable from controls, and no significant differences were noted in the ex vivo assays in these areas. Treatment with DPTVP fully reversed the biochemical parameters altered by Mn. Furthermore, DPTVP treatment was also associated with a reduction in striatal Mn levels. Our results demonstrate that DPTVP has neuroprotective activity against Mn-induced neurotoxicity, which may be attributed to its antioxidant activity and/or its effect on striatal Mn transport.

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