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Liposomes are among the most studied nanostructures. They are effective carriers of active substances both in the clinical field, such as delivering genes and drugs, and in the food industry, such as promoting the controlled release of bioactive substances, including food preservatives. However, toxicological screenings must be performed to ensure the safety of nanoformulations. In this study, the nematode Caenorhabditis elegans was used as an alternative model to investigate the potential in vivo toxicity of nanoliposomes encapsulating the antimicrobial peptide nisin. The effects of liposomes containing nisin, control liposomes, and free nisin were evaluated through the survival rate, lethal dose (LD50), nematode development rate, and oxidative stress status by performing mutant strain, TBARS, and ROS analyses. Due to its low toxicity, it was not possible to experimentally determine the LD50 of liposomes. The survival rates of control liposomes and nisin-loaded liposomes were 94.3 and 73.6%, respectively. The LD50 of free nisin was calculated as 0.239 mg mL−1. Free nisin at a concentration of 0.2 mg mL−1 significantly affected the development of C. elegans, which was 25% smaller than the control and liposome-treated samples. A significant increase in ROS levels was observed after exposure to the highest concentrations of liposomes and free nisin, coinciding with a significant increase in catalase levels. The treatments induced lipid peroxidation as evaluated by TBARS assay. Liposome encapsulation reduces the deleterious effect on C. elegans and can be considered a nontoxic delivery system for nisin. [ABSTRACT FROM AUTHOR]

Inhalation of xenobiotics during manufacture process in chrome plating bath produce hazards to workers' health. Chromium (Cr) is a metal widely used by industry, and its hexavalent (VI) form has been classified as mutagenic and carcinogenic. This study aimed to evaluate the occupational risk of exposure to metals in chrome plating workers. Biological monitoring was performed through quantification of Cr, Pb, As, Ni, and V in blood by ICP-MS in 50 male chrome-plating workers from the exposed group and 50 male non-exposed workers. The inflammatory parameters assessed were β-2 integrin, intercellular adhesion molecule-1 (ICAM-1), and L-selectin expression in lymphocytes. The genotoxicity was evaluated with comet and micronucleus (MN) assays and as a biomarker of oxidative damage the lipid peroxidation (MDA) and protein carbonyl (PCO). The results demonstrated that Cr levels in blood and urine were increased in the exposed group compared to the non-exposed group. Although the biomarkers of exposure proved to be within the levels considered safe in exposed individuals, chrome plating workers presented significantly increase in the percentage of lymphocytes expressing β-2 integrin, ICAM-1, and L-selectin as well as DNA damage (comet assay) and plasmatic MDA and PCO levels. Therefore, it is possible also assign the injuries caused to lipids, proteins, and DNA assessed due to the increased presence of other metals such as Pb, As, Ni, and V in exposed subjects. These results suggest that exposure to xenobiotics present in the occupational environment in chrome plating industry could play a crucial role toward the inflammation, genetic, and oxidative damage. [ABSTRACT FROM AUTHOR]

Companies have been challenged to attend to multiple objectives and to achieve appropriate decisions facing dichotomies mentioned in literature, such as shareholder versus stakeholder; financial versus non-financial; single versus multiple measures. Since the translation of the sustainable development concept to business by the triple bottom line (TBL), there have been attempts to implement operational approaches. This study proposes a model that helps corporate decision-making considering the TBL framework and a stakeholder view. Multi-criteria decision aid methods are used to generate a sustainability balanced single measure and performance indices. We apply the model to a Brazilian electricity corporation, where the indices are calculated from existing GRI indicators, and the use of the model within the company's strategic plan annual review is demonstrated. The findings suggest that the model has the potential to support informed decisions and the integration of corporate sustainability performance measurement and reporting activities with traditional management control systems. [ABSTRACT FROM AUTHOR]

The evaluation of genotoxicity in workers exposed to different toxic agents is very important, especially considering the association between these exposures in a chronic context and DNA damage. Assessing biomarkers of exposure and, when possible, early biomarkers of effect, contributes to elucidating the potential toxic mechanisms involved in genotoxicity and its contribution to chronic non-communicable diseases. In Brazil, the biggest country in South America, workers are exposed to hazardous physical and chemical agents. Considering that these exposures occur, in most cases, throughout the worker's whole life, this is an important public health concern in Brazil. Therefore, this systematic review aims to analyze occupational exposure to chemical and physical agents and the association with DNA damage in studies carried out in Brazil from 1980 to 2021. A systematic and comprehensive literature search was performed in different databases based on occupational exposure to chemical and physical agents and DNA damage. Only full articles on studies that investigated experimental evidence on occupational exposure in Brazil and assessed DNA damage were included, amounting to 89 articles. Five main occupational exposure groups were identified: pesticides (36%), organic solvents (20%), dust and particles (16%), metals (11%), and ionizing radiation (6%). Another group called "others" included studies (11%) that did not fall into these main groups. It was found that comet assay and micronucleus tests are the most adopted methods to detect DNA damage. Occupational exposures were most associated with DNA damage. However, further improvements in study design would be needed to better characterize the association between biomonitoring and DNA damage, particularly to account for confounding factors. [Display omitted] • Review of Brazilian publications evaluating DNA damage and occupational exposure. • The pesticides were the most studied agents by Brazilian scientists. • MN in buccal cells, MN in lymphocytes and comet assay were used to study DNA damage. • Few studies performed other biomarkers of exposure and/or effect. [ABSTRACT FROM AUTHOR]

Currently, a broader set of stakeholders justifies the growing importance of social and environmental disclosure for accountability purposes. However, the quality of information on Sustainability Reports (SR) has been questioned. This study uses content analysis to investigate the accuracy of economic indicators (EC1 to EC9) of Global Reporting Initiative (GRI) standard in the SR in comparison with the information in the financial reports. The sample consists of the Sustainability Reports of 23 companies in the Brazilian power sector, which were published in 2011. The results show that the degree of accuracy is medium or low for all companies, suggesting flaws in the preparation of economic data from the SR, for which companies would be supposedly well prepared, as the accounting systems of the companies contain most of the information necessary especially to meet the Value Added Statement (VAS), the CPC 33 Employee Benefits and CPC 07 Government Subsidies and Assistance. [ABSTRACT FROM AUTHOR]

Several diseases and xenobiotics are known to generate reactive species that may trigger oxidative stress when not properly scavenged by the antioxidant defenses and result in tissue damage. We investigated lipid peroxidation (LPO) as a possible mechanism for tissue damage in some pathologies, in the normal aging process, and in subjects exposed to organic solvents. Plasmatic malondialdehyde (MDA) was quantified by high-performance liquid chromatography with visible wavelength detection in 239 subjects and divided into the following: acute myocardium infarction (AMI), diabetes without complications (D) and hemodialysis (HD) patients; into healthy children, adults, and elderly, all nonexposed to xenobiotics; and into painters occupationally exposed to organic solvents (P). Troponin, glycated hemoglobin, and transminases [aspartate aminotransferase (AST) and alanine aminotransferase] were analyzed. An increase in LPO was observed in AMI, D, HD, and P groups, when compared to healthy adults. No correlation between MDA and age was found. Further, we found positive correlations between MDA versus troponin (r = 0.47), MDA versus HbA1c (r = 0.56), and MDA versus AST (r = 0.41) in AMI, diabetics, and painters, respectively. This work has demonstrated increased lipid and protein damages in myocardium and blood, along with an alteration of hepatic transaminase activities and induction of LPO, suggesting that MDA levels are important to evaluate the extent of tissue alterations and development of acute and chronic conditions. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: : To quantify serum butyrylcholinesterase activity in haemodialysis patients and to evaluate if the homocysteine levels and/or oxidative stress biomarkers have an effect on butyrylcholinesterase. Materials and methods: : Blood samples were collected from patients and healthy subjects (control). The plasma homocysteine and TBARS levels; serum butyrylcholinesterase activity; blood δ aminolevulinic acid dehydratase (ALA-D) activity and methahaemoglobin were analyzed. The mortality of the patients was also evaluated after 3 years. Results: : The homocysteine was increased and butyrylcholinesterase decreased compared to control (p <0.05). TBARS and methahaemoglobin were increased and ALA-D decreased (p <0.05). The following correlations were found: homocysteine with butyrylcholinesterase (−0.44); methahaemoglobin (0.41); ALA-D (−0.68); and TBARS (0.66). The partial correlation between homocysteine with butyrylcholinesterase, withdrawn the effect of TBARS, was −0.30; all p <0.05. Moreover, it was observed that 22% of the patients died due to cardiovascular problems. Conclusion: : Thus, our findings support a direct association between the reduction of butyrylcholinesterase by the increase of homocysteine and an indirect effect by increase in oxidative stress. [Copyright &y& Elsevier]

The present article has the objective to verify if the goals attributed to the bank agencies of a Brazilian institution for performance evaluation are defined in accordance with the variables characteristic of business generation capacity. Regarding the performance presented in 2002, analysis of tree groups are done: agencies that systematically surpass their goals; agencies that present performance in accordance with the expected; and agencies that systematically do not reach their goals. These groups are analyzed in set with 12 groupings of agencies with similar characteristics, identified based on the application of Cluster Analysis. The results point out that the goals attributed to the agencies are coherent with the characteristic variables of this cities business generation potencial. However, for the agencies group that surpass their goals systematically, the study discloses that the goals underestimate their cities and agencies business potencial. The article confirms the Cluster technique contribution for goals attribution. [ABSTRACT FROM AUTHOR]

Vascular endothelial cells play an important role in the control of vascular tone. The reasons for coronary endothelial dysfunction are complex and may involve ischemia/reperfusion injury. We investigated whether endothelial, smooth muscle, and myocardial dysfunction are independent phenomena. Rabbit hearts were rapidly excised without intermittent ischemia, connected to a modified Langendorff apparatus, and perfused with a modified Krebs-Henseleit solution containing bovine erythrocytes. Normoxic control hearts (n = 16) were perfused for 125 min. Postischemic hearts (n = 15) were perfused for 45 min, submitted to global ischemia (20 min) and reperfused (60 min). Both the normoxic and the postischemic hearts were divided into three groups that received either 0.9% NaCl (placebo), or 3-morpholinosydnonimine (SIN-1; 100 μM),or substance P (SP; 5 nM). After SIN-1, CBF in the normoxic hearts was increased by maximum 63% and after SP by 62%. 60 min after the onset of reperfusion, the postischemic hearts of both groups had recovered to 95% LVPmax. In the postischemic hearts, SIN-1 increased CBF still by 58%, while the endothelium-dependent vasomotion was impaired: SP improved CBF by only 9%. The particular protocol permitted differentiation between myocardial and vascular stunning. The results show that, while myocardial function has already recovered, endothelial cells are more severely impaired than smooth muscle cells, and that this injury persists beyond myocardial stunning. Thus, endothelial-dependent dysfunction can still impair vasodilatation while ventricular dysfunction has already resolved. [ABSTRACT FROM AUTHOR]

Among the potential adverse effects of breast cancer treatment, chemotherapy-related cognitive impairment (CRCI) has gained increased attention in the past years. In this review, we provide an overview of the literature regarding CRCI in breast cancer, focusing on three main aspects. The first aspect relates to the molecular mechanisms linking individual drugs commonly used to treat breast cancer and CRCI, which include oxidative stress and inflammation, reduced neurogenesis, reduced levels of specific neurotransmitters, alterations in neuronal dendrites and spines, and impairment in myelin production. The second aspect is related to the clinical characteristics of CRCI in patients with breast cancer treated with different drug combinations. Data suggest the incidence rates of CRCI in breast cancer vary considerably, and may affect more than 50% of treated patients. Both chemotherapy regimens with or without anthracyclines have been associated with CRCI manifestations. While cross-sectional studies suggest the presence of symptoms up to 20 years after treatment, longitudinal studies confirm cognitive impairments lasting for at most 4 years after the end of chemotherapy. The third and final aspect is related to possible therapeutic interventions. Although there is still no standard of care to treat CRCI, several pharmacological and non-pharmacological approaches have shown interesting results. In summary, even if cognitive impairments derived from chemotherapy resolve with time, awareness of CRCI is crucial to provide patients with a better understanding of the syndrome and to offer them the best care directed at improving quality of life. [ABSTRACT FROM AUTHOR]

Bladder cancer is the fourth most common malignancy in men. It can present along the entire continuum of severity, from mild to well‐differentiated disease to extremely malignant tumors with low survival rates. Human RAS genes are the most frequently mutated oncogenes in human cancers, and the critical role of aberrant Ras protein function in carcinogenesis is well established. Therefore, considerable efforts have been devoted to the development of anti‐Ras inhibitors for cancer treatment. This study presents the biphenyl dihydropyrimidinone LaSOM 335 with high activity against T24 bladder cancer cells (IC50 = 10.73 ± 0.53 μM) and selectivity of cytotoxicity for this cancer cell line compared to two non‐cancer cell lines investigated. Furthermore, we also show that this compound reduced vulvar development in the mutant let‐60 gene of Caenorhabditis elegans. Let‐60 is a homolog of the mammalian Ras gene. In addition, we observed that LaSOM 335 inhibits the enzymatic activity of CD73 and decreases CD73 expression. Possibly, this expression decrease is due to downstream EGFR signaling via the Ras–Raf–ERK pathway, that directly regulates CD73 expression via ERK1/2. Evidence suggests that non‐immunomodulating functions of CD73 play an equally important role for cancer cell survival, progression, and migration. Regarding we also notice that LaSOM 335 was safe in the in vivo model of C. elegans. The set of these findings makes this biphenyl dihydropyrimidinone a promising candidate for further investigations in the bladder cancer field. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence of vitamin A deficiency (VAD) in children and associated risk factors. Design: Analysis of data from a cross-sectional multicentre study performed in the primary care units of the municipalities from January to June 2015. The children's legal guardians answered a socio-economic questionnaire, and the children's blood samples were obtained by venipuncture. Plasma retinol was determined by HPLC. Plasma retinol values of <0·70 μmol/l were considered VDA. Poisson multiple regression with robust variance was used. Values of P < 0·05 were considered significant. The data were analysed in the SPSS software, 21.0. Setting: Forty-eight poorest municipalities in the South Region of Brazil. Participants: Children (n 1503) aged 12–59 months. Results: The prevalence of VAD in the sample was 1·9 % (95 % CI (0·5, 6·8)). The following risk factors were associated with the outcome in the final explanatory model: family received Bolsa Familia program benefits (PR = 3·19; 95 % CI (1·69, 6·02)), child was not being breastfed (PR = 5·22; 95 % CI (1·68, 16·18)) and stunting (PR = 4·75; 95 % CI (2·10, 10·73)). Conclusions: VAD did not represent a public health problem for children living in socio-economically vulnerable municipalities in the South Region of Brazil, suggesting a new panorama of this nutritional deficiency even in regions of low socio-economic conditions in these three states. Thus, in view of the current nutritional transition scenario, it is necessary to continuously monitor and improve public policies related to vitamin A supplementation in the country. [ABSTRACT FROM AUTHOR]

DNAJ/HSP40 co-chaperones are integral to the chaperone network, bind client proteins and recruit them to HSP70 for folding. We performed exome sequencing on patients with a presumed hereditary muscle disease and no genetic diagnosis. This identified four individuals from three unrelated families carrying an unreported homozygous stop gain (c.856A > T; p.Lys286Ter), or homozygous missense variants (c.74G > A; p.Arg25Gln and c.785 T > C; p.Leu262Ser) in DNAJB4. Affected patients presented with axial rigidity and early respiratory failure requiring ventilator support between the 1st and 4th decade of life. Selective involvement of the semitendinosus and biceps femoris muscles was seen on MRI scans of the thigh. On biopsy, muscle was myopathic with angular fibers, protein inclusions and occasional rimmed vacuoles. DNAJB4 normally localizes to the Z-disc and was absent from muscle and fibroblasts of affected patients supporting a loss of function. Functional studies confirmed that the p.Lys286Ter and p.Leu262Ser mutant proteins are rapidly degraded in cells. In contrast, the p.Arg25Gln mutant protein is stable but failed to complement for DNAJB function in yeast, disaggregate client proteins or protect from heat shock-induced cell death consistent with its loss of function. DNAJB4 knockout mice had muscle weakness and fiber atrophy with prominent diaphragm involvement and kyphosis. DNAJB4 knockout muscle and myotubes had myofibrillar disorganization and accumulated Z-disc proteins and protein chaperones. These data demonstrate a novel chaperonopathy associated with DNAJB4 causing a myopathy with early respiratory failure. DNAJB4 loss of function variants may lead to the accumulation of DNAJB4 client proteins resulting in muscle dysfunction and degeneration. [ABSTRACT FROM AUTHOR]

People are exposed to pesticides through food, drinking water, and the environment. These compounds are associated with several disorders, such as inflammatory diseases, rheumatoid arthritis, cancer, and a condition related to metabolic syndrome. The immunotoxicants or immunotoxic compounds can cause a wide variety of effects on immune function, altering humoral immunity and cell-mediated immunity, resulting in adverse effects to the body. Here, immune system disorders are highlighted because they are closely linked to multiple organs, including the nervous, endocrine, reproductive, cardiovascular, and respiratory systems, leading to transient or permanent changes. Therefore, this study reviewed the mechanisms involved in the immunotoxicity of fungicides, herbicides, and insecticides in cells, animals, and humans in the past 11 years. According to the studies analyzed, the pesticides interfere with innate and adaptive immune functions, but the effects observed mainly on cellular and humoral immunity were highlighted. These compounds affected specific immune cells, causing apoptosis, changes in factor nuclear kappa B (NF-κB) expression, pro-inflammatory factors interleukin 6 (IL-6), interleukin 8 (IL-8), interferon-gamma (IFN-γ), chemokines (CXCL-c1c), and anti-inflammatory factor, such as interleukin 10 (IL-10). To verify the threats of these compounds, new evaluations with immunotoxicological biomarkers are necessary. Pesticides interfere with the innate and adaptive immune response. Cells, animals and human studies demonstrate the immunotoxicity of pesticides in the cellular and humoral immune response. Fungicides, herbicides, and insecticides alter the immune system by various mechanisms, such as pro-inflammatory and anti-inflammatory factors. [ABSTRACT FROM AUTHOR]

Background and purpose: Mos scales currently used to evaluate spinal muscular atrophy (SMA) patients have only been validated in children. The aim of this study was to assess the construct validity and responsiveness of several outcome measures in adult SMA patients. Methods: Patients older than 15 years and followed up in five referral centres for at least 6 months, between October 2015 and August 2020, with a motor function scale score (Hammersmith Functional Motor Scale Expanded [HFMSE], Revised Upper Limb module [RULM]) were included. Bedside functional scales (Egen Klassification [EK2], Revised Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS‐R]) were also collected when available. Spearman's rho correlations (rs) and Bangdiwala's concordance test (B) were used to evaluate the scales' construct validity. Monthly slopes of change were used to calculate their responsiveness of the scales. Results: The study included 79 SMA patients, followed up for a mean of 16 months. All scales showed strong correlations with each other (rs > 0.70). A floor effect in motor function scales was found in the weakest patients (HFMSE < 5 and RULM < 10), and a ceiling effect was found in stronger patients (HFMSE > 60 and RULM > 35). The ALSFRS‐R (B = 0.72) showed a strong ability to discriminate between walkers, sitters and non‐sitters, and the HFMSE (B = 0.86) between walkers and sitters. The responsiveness was low overall, although in treated patients a moderate responsiveness was found for the ALSFRS‐R and HFMSE in walkers (0.69 and 0.61, respectively) and for EK2 in sitters (0.65) and non‐sitters (0.60). Conclusions: This study shows the validity and limitations of the scales most frequently used to assess adult SMA patients. Overall, bedside functional scales showed some advantages over motor scales, although all showed limited responsiveness. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim was to assess the safety and efficacy of nusinersen in adult 5q spinal muscular atrophy (SMA) patients. Methods: Patients older than 15 years and followed for at least 6 months with one motor scale (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb Module, RULM) in five referral centers were included. The clinical and patients' global impression of change (CGI‐C and PGI‐C) were recorded in treated patients at the last visit. Functional scales (Egen Klassification, EK2; Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS‐R) and the percentage predicted forced vital capacity were collected when available. Results: Seventy‐nine SMA patients (39 treated with nusinersen) were included. Compared with untreated patients, treated patients showed a significant improvement of 2 points (±0.46) in RULM (p < 0.001) after 6 months. After a mean follow‐up of 16 months, nusinersen treatment was associated with a significant improvement in HFMSE (odds ratio [OR] 1.15, p = 0.006), the 6‐min walk test (OR = 1.07, p < 0.001) and the EK2 (OR = 0.81, p = 0.001). Compared with untreated patients, more treated patients experienced clinically meaningful improvements in all scales, but these differences were statistically significant only for RULM (p = 0.033), ALSFRS‐R (p = 0.005) and EK2 (p < 0.001). According to the CGI‐C and PGI‐C, 64.1% and 61.5% of treated patients improved with treatment. Being a non‐sitter was associated with less response to treatment, whilst a longer time of treatment was associated with better response. Most treated patients (77%) presented at least one adverse event, mostly mild. Conclusions: Nusinersen treatment is associated with some improvements in adult SMA patients. Most severely affected patients with complex spines are probably those with the most unfavorable risk–benefit ratio. [ABSTRACT FROM AUTHOR]

This study associates blood antioxidants like copper (Cu), manganese (Mn), selenium (Se), zinc (Zn), β-carotene, lycopene and vitamins (A and E) to sociodemographic features and seasonality in communities from the Tapajós River region, Brazilian Amazon. We observed increased Mn, Se and Zn levels compared to the average Brazilian population, whereas this is only the case for β-carotene in the rainy season. Lycopene levels fall within the reference range, although lower than those found in other Brazilian regions. Cu, Se, Zn, β-carotene, lycopene and vitamin E levels vary among seasons. β-carotene, Mn and Se vary among communities. Se and Zn vary with smoking habits and sex, respectively. In addition, β-carotene and vitamins (A and E) are altered by alcohol consumption. Villagers who both farmed and fished present higher Cu and lower β-carotene levels than participants with a single occupation. Vitamin E levels depend upon the individual state of origin. These data provide important baseline information for antioxidant status in this Amazonian riparian population. [ABSTRACT FROM AUTHOR]

Abstract: The use of synthetic pharmaceuticals in phytotherapeutics can be defined as an illegal practice, since these compounds are normally present as non-declared compounds in the phytotherapeutical formulations. This work aims to show the development of an analytical method based on adsorptive cathodic stripping voltammetry (AdCSV) for the simultaneous determination of 1,4-benzodiazepines and amfepramone. The developed method was used to measure seven benzodiazepines (clonazepam, flurazepam, alprazolam, midazolam, medazepam, chlordiazepoxide, and diazepam) and amfepramone in slimming formulations that have been commercialized in Brazil. This method permits the screening of adulterant classes in a single voltammetric run by using a hanging mercury drop electrode as a working electrode and Ringer buffer (pH 10.0) as a supporting electrolyte. Recovery values ranging from 92.0% to 117.0% demonstrate the reliability of the method in the determination of adulterants in real samples. Among the 12 samples studied by the proposed method, 4 were demonstrated to be adulterated by 1,4-benzodiazepines. [Copyright &y& Elsevier]

Arsenic (As) causes health effects, especially cancer. Rice (Oryza sativa L.) can contain high As concentrations. Using ICP-MS, we quantified the total As (tAs) levels in the main brands of rice (n = 103) and infant cereals (n = 27) consumed by Brazilians. The levels were compared to the maximum limits prescribed by regulatory agencies. We estimated the daily intake (EDI) of As by Brazilians by combining the mean As concentration determined in the white rice samples with per capita daily consumption divided by the average body weight as reported by the Brazilian Institute of Geography and Statistics in 2010. The possible health risk for consumers was assessed by calculating the margin of exposure (MOE) as prescribed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Moreover, tAs was determined in 11 pesticides used by Brazilian farmers. The tAs levels in the rice ranged from 0.003 to 1.3 mg kg−1. Approximately 27% of the white rice contained tAs levels above the limit set by Mercosul (0.3 mg kg−1) and 45% were above the limit set by the European Commission (0.2 mg kg−1). In the infant cereals, tAs levels ranged from 0.003 to 0.243 mg kg−1. In the pesticides, tAs levels ranged from 0.005 to 0.315 mg L−1. The EDI showed that, on average, Brazilians consume 4.13 µg As kg−1 BW weekly. In addition, a low MOE was observed, demonstrating that high use of rice presents a risk of high inorganic (iAs) exposure, which represents a public health concern. [ABSTRACT FROM AUTHOR]

Introduction: Our goal was to demonstrate the effects of occupational exposure to antineoplastic drugs on oxidative stress parameters and DNA damage in health professionals who manipulate and administer antineoplastic drugs in a University Hospital in Southern Brazil. Methods: The case-control study with a longitudinal design, involved 64 individuals, 29 of them pharmacists, pharmacy technicians and nurses who were occupationally exposed to antineoplastic drugs and 35 professionals who were not exposed. Gene mutations were determined by micronucleus from salivary fluid; DNA damage by comet assay and oxidative stress parameters in whole blood were also evaluated. Results: All workers exposed to antineoplastic drugs used personal protective equipment (PPE). It was demonstrated that the total nonprotein thiol and thiobarbituric acid reactive substances levels showed interaction between group and time, with higher levels one week after handling/administration of antineoplastic drugs in the exposed group (GEE, p ≤ 0.0001 and p = 0,013, respectively). Additionally, there was a group effect on the activities of the catalase and glutathione peroxidase antioxidant enzymes (GEE, p = 0.027 and p ≤ 0.0001, respectively), and workers occupationally exposed to antineoplastic drugs had higher enzyme activities compared to those not exposed. No genotoxic damage was demonstrated through the evaluated parameters. Conclusions: Despite the correct use of PPE, professionals occupationally exposed to antineoplastic drugs were more susceptible to oxidative stress than those not exposed. The evaluation of the studied parameters is especially important for the definition of conducts and practices in the area, always in search of guaranteeing the establishment of a rational policy to protect workers' health. [ABSTRACT FROM AUTHOR]

Chronic opioid use changes brain chemistry in areas related to reward processes, memory, decision-making, and addiction. Both neurons and astrocytes are affected, ultimately leading to dependence. Passiflora incarnata L. (Passifloraceae) is the basis of frequently used herbals to manage anxiety and insomnia, with proven central nervous system depressant effects. Anti-addiction properties of P. incarnata have been reported. The aim of this study was to investigate the effect of a commercial extract of Passiflora incarnata (Sintocalmy®, Aché Laboratory) in the naloxone-induced jumping mice model of morphine withdrawal. In addition, glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B) levels were assessed in the frontal cortex and hippocampus, and DNA damage was verified on blood cells. In order to improve solubilization a Sintocalmy methanol extract (SME) was used. SME is mainly composed by flavonoids isovitexin and vitexin. The effects of SME 50, 100 and 200 mg/kg (i.p.) were evaluated in the naloxone-induced withdrawal syndrome in mice. SME 50 and SME 100 mg/kg decreased naloxone-induced jumping in morphine-dependent mice without reducing locomotor activity. No alterations were found in GFAP levels, however SME 50 mg/kg prevented the S100B increase in the frontal cortex and DNA damage. This study shows anti-addiction effects for a commercial standardized extract of P. incarnata and suggests the relevance of proper clinical assessment. [ABSTRACT FROM AUTHOR]

Dihydropyrimidinone/thiones (DHPMs) are heterocycles widely explored due to their ability to interact with different pharmacological targets. We report herein the C–N axial chirality in a DHPM scaffold with the presence of various substituents at the ortho‐position of the aromatic ring linked to the N1. This structural feature produced atropisomerism due to the restricted rotation around the C−N bond. The atropisomerism in DHPMs was investigated by NMR, HPLC, and in silico experiments. The effect of the solvent, microwave radiation, temperature, and substituent at the ortho position on the selectivity of the reaction was examined. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a mycotoxin found in grape products and oxidative stress has been reported as an important mechanism involved in its toxicity, classified as possible carcinogenic to humans. Conversely, phenolics are known bioactive compounds in grapes and display great antioxidant properties. However, the biological effects of the concomitant presence of phenolic compounds and OTA remains unclear. The aim of this study was to evaluate, for the first time, the effect of OTA presence in Cabernet Sauvignon wine on antioxidant activity in vitro and on oxidative stress markers in vivo. In addition, the phenolic composition of wine was evaluated by LC-DAD-MS/MS. In vitro assays were based on spectrophotometric methods, while in vivo assays were performed evaluating oxidative stress markers in the nematode Caenorhabditis elegans, an alternative model to animal testing. A total of 23 phenolic compounds were identified in the Cabernet sauvignon red wine, including the anthocyanins delphinidin-3-O-glicoside and malvidin-3-O-glicoside, the flavonol quercetin-3-O-glucuronide and the phenolic acids caffeic, verbascoside and caftaric. Trans-resveratrol and trans-piceid were the only stilbenes found in the samples. OTA presence in the red wine was accompanied by reduction in GSH content and increase in hydroxyl radical generation in vitro. The presence of OTA in wine also increased lipoperoxidation and induced overexpression of the antioxidant enzymes superoxide dismutase and catalase in vivo. This study demonstrates that OTA presence in red wine can reduce its antioxidant potential in vitro and induces oxidative stress in vivo, without affecting the phenolic compounds levels in the samples. Thus, this work provides insights into the negative effects of the presence of OTA in wine, not only by its known toxicity, but also by prejudicing the antioxidant potential of wine. It is important to be aware of these effects when developing a complete description of OTA toxicity in humans. [ABSTRACT FROM AUTHOR]

Lycorine is an Amaryllidaceae alkaloid that presents anti-Trichomonas vaginalis activity. T. vaginalis causes trichomoniasis, the most common non-viral sexually transmitted infection. The modulation of T. vaginalis purinergic signaling through the ectonucleotidases, nucleoside triphosphate diphosphohydrolase (NTPDase), and ecto-5′-nucleotidase represents new targets for combating the parasite. With this knowledge, the aim of this study was to investigate whether NTPDase and ecto-5′-nucleotidase inhibition by lycorine could lead to extracellular ATP accumulation. Moreover, the lycorine effect on the reactive oxygen species (ROS) production by neutrophils and parasites was evaluated as well as the alkaloid toxicity. The metabolism of purines was assessed by HPLC. ROS production was measured by flow cytometry. Cytotoxicity against epithelial vaginal cells and fibroblasts was tested, as well as the hemolytic effect of lycorine and its in vivo toxicity in Galleria mellonella larvae. Our findings showed that lycorine caused ATP accumulation due to NTPDase inhibition. The alkaloid did not affect the ROS production by T. vaginalis; however, it increased ROS levels in neutrophils incubated with lycorine-treated trophozoites. Lycorine was cytotoxic against vaginal epithelial cells and fibroblasts; conversely, it was not hemolytic neither exhibited toxicity against the in vivo model of G. mellonella larvae. Overall, besides having anti-T. vaginalis activity, lycorine modulates ectonucleotidases and stimulates neutrophils to secrete ROS. This mechanism of action exerted by the alkaloid could enhance the susceptibility of T. vaginalis to host immune cell, contributing to protozoan clearance. [ABSTRACT FROM AUTHOR]

Introduction: Nimesulide is a potent anti-inflammatory with rapid and long-lasting effects, but also with a high risk of hepatotoxicity. Objective: This work aimed to prevent nimesulide-induced hepatotoxicity through the association of nimesulide with a hepatoprotective agent. Materials and Methods: First, we tested three hepatoprotective agents: N-acetylcysteine, L-carnitine, and Gingko biloba extract in an in vitro hepatic cell model. Both N-acetylcysteine and G. biloba showed promisor results. We selected N-acetylcysteine to continue the studies in an animal model. In vivo study was performed using male Wistar rats divided in 4 groups: control, nimesulide (100mg/kg/day), nimesulide (100mg/kg/day) + N-acetylcysteine (100mg/kg/day) and N-acetylcysteine alone (100mg/kg/day). Treatments were given by gavage, daily, for 15 days. Results: Animals receiving nimesulide alone showed lower body weight gain compared to control. Body weight gain in the nimesulide + N-acetylcysteine group was higher than nimesulide alone, evidencing lower toxicity. However, the body weight gain of the nimesulide + N-acetylcysteine group was still lower than the control animals. Animals treated with nimesulide alone presented an increased relative mass of heart, liver, and spleen and significant hepatic damage seen in microscopy when compared to other groups. N-acetylcysteine co-administered with nimesulide prevented the increased heart mass, but the same was not true with liver and spleen. Conclusions: This work evidence partial protection elicited by the association of N-acetylcysteine and nimesulide against nimesulide-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Background and Objectives: Smokers currently have no defined restrictions for blood donation. However, cigarette smoke contains toxic substances such as carbon monoxide (CO) and trace elements that can affect the packed red blood cells (PRBCs) quality and safety of transfusion. This study evaluated the effects of smoking on the concentration of essential and trace elements and on carboxyhemoglobin (COHb) levels in PRBCs from smoker donors. Materials and Methods: A matched case–control study was conducted to compare COHb levels, determined by the CO‐oximetry method, and levels of trace (Cd, Pb, Cr, Ni, As and Hg) and essential (Ca, Mg, Cu, Fe, Mn, Mo, Se and Zn) elements evaluated by inductively coupled plasma mass spectrometry, in PRBCs from smoker (n = 36) and non‐smoker (n = 36) donors at Hospital de Clínicas de Porto Alegre, Brazil. Results: Mean COHb level was 14 times higher in the PRBCs obtained from smoker donors (5·9 [4·0–9·1] vs. 0·4 [0·2–0·8]%). Cadmium (1·0 [1·0‐1·8] μg/l vs. undetectable) and lead (27 [21–36] vs. 19 [14–26] μg/l) levels were significantly higher in the PRBCs from smokers. Moreover, except for molybdenum, levels of all essential elements were lower in smoker PRBCs. Conclusion: The PRBCs donated by smokers contain toxic elements that are probably not safe for transfusion in children. Our results might support changes in the current guidelines of blood banks to improve the transfusion safety through inclusion of inquiry about smoking in the clinical screening, labelling and reserve PRBCs from smoker donors for adults or less critical recipients. [ABSTRACT FROM AUTHOR]

Degradation kinetics of oral anticoagulant rivaroxaban (RIV) was assessed in acid and alkaline media and while exposed to UVC radiation. Among all stress conditions tested, kinetic degradation process was better described by a zero-order model. A stability indicating method was validated for the analysis of the anticoagulant RIV in tablets by high-performance liquid chromatography. Robustness was evaluated with a two-level Plackett–Burman experimental design. The effect of acute exposition of the human hepatoblastoma HepG2 cell line to RIV stressed samples (100 and 500 µM) was assessed through in vitro toxicity tests. MTT reduction, neutral red uptake, mitochondrial membrane potential, and low molecular weight DNA diffusion assays were employed for cytotoxicity evaluation (5×104 cells/well). The genotoxic potential was assessed by comet assay (2×104 cells/well). Acute toxicity to HepG2 cells was assessed after 24 h incubation with sample solutions, for each test. A direct relationship between the increased amount of alkaline degradation products and higher cytotoxic potential was found. Results obtained by viability assay investigations support the concerns on risks associated with acute toxicity and genotoxicity of pharmaceutical samples containing degradation products as impurities. [ABSTRACT FROM AUTHOR]

The neonicotinoid imidacloprid was promoted in the market because of widespread resistance to other insecticides, plus its low mammalian impact and higher specific toxicity towards insects. This study aimed to evaluate the immunomodulatory effect of imidacloprid on macrophages. RAW 264.7 cells were incubated to 0–4000 mg/L of imidacloprid for 24 and 96 h. Imidacloprid presented a concentration-dependent cytotoxicity after 24 h and 96 h incubation for MTT reduction (3-(4,5-dimethyl-thiazol-2-yl)− 2,5-diphenyltetrazolium bromide) (EC 50 519.6 and 324.6 mg/L, respectively) and Neutral Red (3-amino-7-dimethylamino-2-methylphenazine hydrochloride) assays (EC 50 1139.0 and 324.2 mg/L, respectively). Moreover, imidacloprid decreased the cells' inflammatory response and promoted a mitochondrial depolarization. The complex II and succinate dehydrogenase (SDH) activities in RAW 264.7 cells incubated with imidacloprid increased more at 24 h. These results suggest that imidacloprid exerts an immunomodulatory effect and mitochondria can act as regulator of innate immune responses in the cytotoxicity mediated by the insecticide in RAW 264.7 cells. [Display omitted] • A commercial formulation of imidacloprid impaired the inflammatory response in RAW 264.7 cells; • The immunotoxic effects were associated with long term exposure to imidacloprid; • The mitochondria is a primary target of imidacloprid cytotoxicity. [ABSTRACT FROM AUTHOR]

• Graphene oxide nanoparticles induced cytotoxicity in H9c2 cells. • Graphene oxide nanoparticles induced mitochondrial hyperpolarization in H9c2 cells. • Graphene oxide nanoparticles elicited an increase in free radicals in H9c2 cells. • DNA damage was related to graphene oxide nanoparticles cytotoxicity. Graphene is a two-dimensional (2D) monolayer of carbon atoms, tightly packed, forming a honey comb crystal lattice, with physical, chemical, and mechanical properties greatly used for energy storage, electrochemical devices, and in nanomedicine. Many studies showed that nanomaterials have side-effects on health. At present, there is a lack of information regarding graphene and its derivatives including their cardiotoxic properties. The aim of the present study was to evaluate the toxicity of nano-graphene oxide (nano-GO) in the rat cardiomyoblast cell line H9c2 and the involvement of oxidative processes. The cell viability was evaluated with the fluorescein diacetate (FDA)/propidium iodide (PI) and in the trypan blue exclusion assay, furthermore mitochondrial membrane potential and production of free radicals were measured. Genotoxicity was evaluated in comet assay and low molecular weight DNA experiment. Reduction of cell viability with 20, 40, 60, 80, and 100 μg/mL nano-GO was observed after 24 h incubation. Besides, nano-GO induced a mitochondrial hyperpolarization and a significant increase of free radicals production in the same concentrations. DNA breaks were observed at 40, 60, 80, and 100 μg/mL. This DNA damage was accompanied by a significant increase in LMW DNA only at 40 μg/mL. In conclusion, the nano-GO caused cardiotoxicity in our in vitro model, with mitochondrial disturbances, generation of reactive species and interactions with DNA, indicating the importance of the further evaluation of the safety of nanomaterials. [ABSTRACT FROM AUTHOR]

Abstract Endocrine disrupting chemicals (EDCs), including pesticides and metals, are present in rural areas, endangering the health of exposed populations. This work aimed to investigate the possible association between the exposure to these xenobiotics and thyroid dysfunction in children living in a rural community of Southern Brazil. Fifty-four children aged 5–16 years participated in this study. Peripheral biomarker evaluations were performed in periods of low and high exposure to pesticides. Thyroid ultrasonography was evaluated in the high exposure period. Blood levels of chromium (Cr), manganese (Mn), mercury (Hg), and lead (Pb), as well as hair Pb levels were positively correlated with thyroid stimulating hormone (TSH) concentrations and negatively associated with free thyroxine (fT4) levels in the low exposure period. Prolactin was positively associated with hair Mn in both periods. In the ultrasound tests, the majority of children presented a normal echogenicity of thyroid. Glucose was inversely associated with the biomarker of exposure to cholinesterase inhibitor insecticides, butyrylcholinesterase (BuChE). Lipid profile was above the recommended levels in both periods. In summary, our results show that children environmentally exposed to a mixture of xenobiotics in an agricultural community may have health impairments, especially on thyroid function, dyslipidemia, and glucose homeostasis disruption. Highlights • Rural children had elevated blood and hair Mn and Cr levels. • Disruption on thyroid function can be related to metals exposure in rural areas. • Dyslipidemia is associated to thyroid dysfunction in children exposed to metals. • Cholinesterase inhibitors insecticides affect the glucose homeostasis of children. • Children exposed to high levels of Mn can be evaluated through the prolactin. [ABSTRACT FROM AUTHOR]

Benzene is a recognized human carcinogen; however, there are still some gaps in the knowledge regarding the mechanism of toxicity of this organic solvent and potential early biomarkers for the damage caused by it. In a previous study, our research group demonstrated that the adhesion molecules of the immune system (B7.1 and B7.2) could be potential biomarkers in the early detection of immunotoxicity caused by benzene exposure. Therefore, this study was developed to deepen the understanding regarding this important topic, aiming to contribute to the comprehension of the benzene toxicity mechanism mediated by B7.1 and B7.2 and its potential association with the risk of carcinogenicity. B7.1 and B7.2 protein expression in blood monocytes and B7.1 and B7.2 gene expression in PBMCs were evaluated. Additionally, complement C3 and C4 levels in serum were measured, as well as p53 gene expression in PBMCs. Seventy-four gas station workers (GSW group) and 71 non-occupationally exposed subjects (NEG) were evaluated. Our results demonstrated decreased levels of B7.1 and B7.2 protein and gene expression in the GSW group compared to the NEG (n = 71) ( p  < 0.01). Along the same lines, decreased levels of the complement system were observed in the GSW group ( p  < 0.01), demonstrating the impairment of this immune system pathway as well. Additionally, a reduction was observed in p53 gene expression in the GSA group ( p  < 0.01). These alterations were associated with both the benzene exposure biomarker evaluated, urinary trans, trans-muconic acid, and with exposure time ( p  < 0.05). Moreover, strong correlations were observed between the gene expression of p53 vs. B7.1 (r = 0.830; p  < 0.001), p53 vs. B7.2 (r = 0.685; p  < 0.001), and B7.1 vs. B7.2 (r = 0.702; p  < 0.001). Taken together, these results demonstrate that the immune system co-stimulatory molecule pathway is affected by benzene exposure. Also, the decrease in p53 gene expression, even at low exposure levels, reinforces the carcinogenicity effect of benzene in this pathway. Therefore, our results suggest that the promotion of immune evasion together with a decrease in p53 gene expression may play an important role in the benzene toxicity mechanism. However, further and targeted studies are needed to confirm this proposition. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the acute toxicity of the association of energy drink and alcohol in male Wistar rats. Animals were treated by oral gavage with 10 ml/kg distilled water (control); 10 ml/kg energy drink (ED10); 3.2 mg/kg caffeine + 40 mg/kg taurine; 2 g/kg alcohol 20%; 2 g/kg alcohol 20% + ED10; and 2 g/kg alcohol 20% + 3.2 mg/kg caffeine + 40 mg/kg taurine. Behavioral alterations were observed for 6 h after treatment. Animals presented significant differences in the frequency of rearing, ambulation, grooming, wakefulness and tachypnea along time. Caffeine + taurine increased the levels of TBARS and total thiols in kidneys. ED10 increased lipoperoxidation in liver. The association of ED10 + alcohol induced nephrotoxicity observed by the increase of urinary N -acetyl-β- d -glucosaminidase (NAG) activity. Histopathological analysis showed the presence of congestion and hydropic and hyaline degenerations in the livers of ED10 + alcohol treated rats, and hemorrhage in the liver of alcohol + caffeine + taurine group. In kidneys, hyaline degeneration was observed in ED10; ED10 + alcohol; caffeine + taurine; and alcohol + caffeine + taurine. Hemorrhage was present in the kidneys of all groups. The combination of energy drinks and alcohol is not safe for the consumers. Therefore, precautionary measures should be disseminated among risk populations, especially the teenagers. [ABSTRACT FROM AUTHOR]

Workers involved in mining activities are exposed to crystalline silica, which leads to constant pulmonary inflammatory reactions and severe oxidative damage, resulting in silicosis. In this work, we aimed to evaluate inflammatory and oxidative stress parameters as potential early biomarkers of effect to assess crystalline silica toxicity in workers who had occupational exposure during mining. We enrolled 38 workers exposed to crystalline silica (WECS), 24 individuals with silicosis (IWS), and 30 occupationally unexposed workers (OUW), a total of 92 participants. The WECS were divided into 2 groups, according to the time of exposure: 19 workers with 1–15 years of occupational exposure (WECS I) and 19 workers with >16 years of occupational exposure (WECS II). The inflammatory parameters assessed were L-selectin, β-2 integrin, and intercellular adhesion molecule-1 (ICAM-1) surface protein expression in lymphocytes and monocytes, complement C3 and C4, high sensitivity C-reactive protein (hsCRP), and adenosine deaminase (ADA) in serum. Plasma levels of malondialdehyde (MDA) and serum levels of vitamin C were determined as biomarkers of oxidative stress. Biochemical and hematological parameters were also investigated. L-selectin surface protein expression was significantly decreased in the WECS II group ( p  < 0.05), indicating the importance of this immune system component as a potential marker of crystalline-silica-induced toxicity. The MDA levels were significantly increased in the WECS I, WECS II, and IWS groups compared to the OUW group ( p  < 0.05). Vitamin C levels were decreased, while C3, hsCRP, ADA, and aspartate aminotransferase (AST) levels were increased in the IWS group compared to the OUW group ( p  < 0.05). Glucose and urea levels were significantly higher in the WECS I, II, and IWS groups compared to the OUW group ( p  < 0.05). Negative partial association was found between L-selectin and time of exposure ( p  < 0.001), supporting the relevance of this biomarker evaluation in long-term exposure to crystalline silica. Significant associations were also observed among inflammatory and oxidative stress biomarkers. Therefore, our results demonstrated the relevance of L-selectin as a potential peripheral biomarker for monitoring crystalline silica-induced toxicity in miners after chronic exposure, before silicosis has developed. However, more studies are necessary for better understanding of the use L-selectin as an early biomarker in exposed workers. [ABSTRACT FROM AUTHOR]

Microcystin-LR (MIC-LR) is a hepatotoxin, with toxicity mechanisms linked to oxidative stress. Besides, neurotoxic effects of MIC-LR have recently been described. Herein, we evaluated the effects of environmentally important concentrations of MIC-LR (1, 10, 100, 250, and 500 μg/L) on oxidative stress markers and the survival rate of the nematode Caenorhabditis elegans (C. elegans) . In addition, a possible protective effect of the carotenoid lutein (LUT) extracted from marigold flowers against MIC-LR toxicity was investigated. Higher concentrations (250 and 500 μg/L) of MIC-LR induced the generation of reactive oxygen species (ROS) and resulted in a survival loss in C elegans . Meanwhile, all MIC-LR concentrations caused an increase in the superoxide dismutase (SOD) expression, while catalase (CAT) expression was only affected at 500 μg/L. The carotenoid LUT prevented the ROS generation, impairment in the CAT expression, and the survival loss induced by MIC-LR in C. elegans . Our results confirm the toxicity of MIC-LR even in a liver-lacking invertebrate and the involvement of oxidative events in this response. Additionally, LUT appears to be able to mitigate the MIC-LR toxic effects. [ABSTRACT FROM AUTHOR]

[Display omitted] Etidocaine (EDC) is a long-acting local anesthetic of the aminoamide family whose use was discontinued in 2008 for alleged toxicity issues. Ionic gradient liposomes (IGL) are nanostructured carriers for which an inner/outer gradient of ions increases drug upload. This work describes IGL EDC , a formulation optimized by Design of Experiments , composed of hydrogenated soy phosphatidylcholine:cholesterol:EDC, and characterized by DLS, NTA, TEM/Cryo-TEM, DSC and 1H NMR. The optimized IGL showed significant encapsulation efficiency (41 %), good shelf stability (180 days) and evidence of EDC interaction with the lipid bilayer (as seen by DSC and 1H NMR results) that confirms its membrane permeation. In vitro (release kinetics and cytotoxicity) tests showed that the encapsulation of EDC into the IGL promoted sustained release for 24 h and decreased by 50 % the intrinsic toxicity of EDC to Schwann cells. In vivo IGL EDC decreased the toxicity of EDC to Caenorhabditis elegans by 25 % and extended its anesthetic effect by one hour, after infiltrative administration, at clinically used (0.5 %) concentration, in rats. Thus, this novel drug delivery system is a promise for the possible reintroduction of EDC in clinics, aiming at the control of operative and postoperative pain. [ABSTRACT FROM AUTHOR]

This review aimed to investigate possible protective or deleterious effects of polyphenol-rich foods (PRF) on chronic diseases, e.g. cardiovascular, and in pregnant women, along with their antioxidant and anti-inflammatory action. A great variety of foods and beverages, such as herbal teas, grape and orange derivatives, dark chocolate, and many others contain high concentrations of flavonoids and are freely consumed by the general population. In humans, PRF consumption reduces lipid peroxidation, and several studies have shown a positive correlation between an increased consumption of PRF and a decrease in the incidence of cardiovascular disease. On the other hand, current studies have suggested that maternal ingestion of PRF, especially during the third trimester of pregnancy, could be associated to fetal ductal constriction (DC). Fetuses exposed to this type of diet show higher ductal velocities and lower pulsatility indexes, as well as larger right ventricles than those exposed to minimal amounts of these substances. The underlying mechanism involved in these conditions has not been entirely elucidated, but it seems to be a result of the antioxidant and anti-inflammatory effects of polyphenols by some pathway. Furthermore, taking into account the deleterious effect in late-pregnancy against the numerous positive effects associated to polyphenols, this dual behavior deserves attention particularly to control the dietary ingestion of PRF during gestation. In this line, same PRF, natural constituents of human diet, may represent risk to fetal in late pregnancy compared to the use of nonsteroidal anti-inflammatory drugs. [ABSTRACT FROM PUBLISHER]

Women are employed in increasing numbers as gasoline station attendants, a work category with risk of exposure to benzene. We have assessed the effect of gender on biomarkers of occupational benzene exposure. Gasoline station attendants (20 men and 20 women) and 40 control individuals (20 men and 20 women) with no history of occupational benzene exposure were evaluated. Benzene exposure was monitoring by environmental and biological measurements. Urinary trans , trans -muconic acid levels, well-known genetic and hematological alterations linked to benzene exposure, and non-cancer effects on the immune, hepatic, and renal systems were investigated. Our results suggest a potential effect of gender on some effects of occupational benzene exposure, particularly the hematological parameters and trans , trans -muconic acid levels. Despite limitations of our study, our findings provide important considerations about occupational exposure of women to benzene and may contribute to the development of occupational protection standards. [ABSTRACT FROM AUTHOR]

The transgenic soy monoculture demands supplementation with pesticides. The aim of this study was to evaluate the individual and mixture effects of fipronil, glyphosate and imidacloprid in human HepG2 cells. Cytotoxicity was evaluated after 48-h incubations through MTT reduction and neutral red uptake assays. Free radicals production, mitochondrial membrane potential, DNA damage, and release of liver enzymes were also evaluated. Data obtained for individual agents were used to compute the additivity expectations for two mixtures of definite composition (one equipotent mixture, based in the EC 50 values achieved in the MTT assay; the other one based in the acceptable daily intake of each pesticide), using the models of concentration addition and independent action. The EC 50 values for fipronil, glyphosate and imidacloprid were 37.59, 41.13, and 663.66 mg/L, respectively. The mixtures of pesticides elicited significant synergistic effects (p < 0.05), which were greater than the expected by both addictive predictions. Decreased in mitochondrial membrane potential and increased in the transaminases enzymatic activities were observed. As they occur simultaneously, interactions between pesticides, even at non-effective single levels, can reverberate in significant deleterious effects, justifying the need for a more realistic approach in safety evaluations to better predict the effects to human health. • Fipronil, glyphosate, and imidacloprid acted synergistically on toxicity. • Fipronil and glyphosate disrupt the mitochondrial membrane potential. • Fipronil, glyphosate, and their mixtures increase liver enzymes activities. [ABSTRACT FROM AUTHOR]

Imidacloprid (IMI) is a neonicotinoid insecticide employed worldwide for crop protection. IMI's mode of action occurs through the agonism of postsynaptic nicotinic acetylcholine receptors (nAChRs), with high specificity for insect nAChRs although there are reports of mammals' toxicity. Studies on IMI's neurotoxicity are not conclusive; therefore, the aim of this study was to evaluate the subchronic toxic effects of an IMI based commercial pesticide on rats. Adult male Wistar rats received an IMI suspension via the oral route at doses of 1.5, 5, and 15 mg/kg for 45 consecutive days. IMI caused an increase in rearing and time spent at the periphery in the locomotor activity test and a decrease in time spent to finish the OX maze task (p < 0.05; ANOVA/Bonferroni). In blood, there was a decrease in mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration (p < 0.05; ANOVA/Bonferroni) and an increase in serum butyrylcholinesterase activity (p < 0.001; ANOVA/Bonferroni). Therefore, subchronic administration of an IMI-based-pesticide caused behavioral and systemic impairments in rats. • Imidacloprid increased rearing in rats. • Imidacloprid increased time spent at the periphery in the locomotor activity test. • Imidacloprid decreased the time spent to finish the OX maze task. • Imidacloprid decreased mean corpuscular hemoglobin in rats. • Imidacloprid increased serum butyrylcholinesterase in rats. [ABSTRACT FROM AUTHOR]

Environmental exposure to manganese (Mn) results in several toxic effects, mainly neurotoxicity. This study investigated associations among Mn exposure, neuropsychological performance, biomarkers of oxidative damage and early kidney dysfunction in children aged 6–12 years old. Sixty-three children were enrolled in this study, being 43 from a rural area and 20 from an urban area. Manganese was quantified in blood (B-Mn), hair (H-Mn) and drinking water using inductively coupled plasma mass spectrometry (ICP-MS). The neuropsychological functions assessed were attention, perception, working memory, phonological awareness and executive functions – inhibition. The Intelligence quotient (IQ) was also evaluated. The biomarkers malondialdehyde (MDA), protein carbonyls (PCO), δ-aminolevulinate dehydratase (ALA-D), reactivation indexes with dithiothreitol (ALA-RE/DTT) and ZnCl 2 (ALA-RE/ZnCl 2 ), non-protein thiol groups, as well as microalbuminuria (mALB) level and N-acetyl-β-D-glucosaminidase (NAG) activity were assessed. The results demonstrated that Mn levels in blood, hair and drinking water were higher in rural children than in urban children ( p <0.01). Adjusted for potential confounding factors, IQ, age, gender and parents' education, significant associations were observed mainly between B-Mn and visual attention (β=0.649; p <0.001). Moreover, B-Mn was negatively associated with visual perception and phonological awareness. H-Mn was inversely associated with working memory, and Mn levels from drinking water with written language and executive functions – inhibition. Rural children showed a significant increase in oxidative damage to proteins and lipids, as well as alteration in kidney function biomarkers ( p <0.05). Moreover, significant associations were found between B-Mn, H-Mn and Mn levels in drinking water and biomarkers of oxidative damage and kidney function, besides between some oxidative stress biomarkers and neuropsychological tasks ( p <0.05). The findings of this study suggest an important association between environmental exposure to Mn and toxic effects on neuropsychological function, oxidative damage and kidney function in children. [ABSTRACT FROM AUTHOR]

Trichomonas vaginalis is the aethiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease in the world. The purinergic signaling pathway is mediated by extracellular nucleotides and nucleosides that are involved in many biological effects as neurotransmission, immunomodulation and inflammation. Extracellular nucleotides can be hydrolyzed by a family of enzymes known as ectonucleotidases including the ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) family which hydrolyses nucleosides triphosphate and diphosphate as preferential substrates and ecto-5′-nucleotidase which catalyzes the conversion of monophosphates into nucleosides. In T. vaginalis the E- NTPDase and ecto-5′-nucleotidase activities upon adenine nucleotides have already been characterized in intact trophozoites but little is known concerning guanine nucleotides and nucleoside. These enzymes may exert a crucial role on nucleoside generation, providing the purine sources for the synthesis de novo of these essential nutrients, sustaining parasite growth and survival. In this study, we investigated the hydrolysis profile of guanine-related nucleotides and nucleoside in intact trophozoites from long-term-grown and fresh clinical isolates of T. vaginalis. Knowing that guanine nucleotides are also substrates for T. vaginalis ectoenzymes, we evaluated the profile of nucleotides consumption and guanosine uptake in trophozoites submitted to a serum limitation condition. Results show that guanine nucleotides (GTP, GDP, GMP) were substrates for T. vaginalis ectonucleotidases, with expected kinetic parameters for this enzyme family. Different T. vaginalis isolates (two from the ATCC and nine fresh clinical isolates) presented a heterogeneous hydrolysis profile. The serum culture condition increased E-NTPDase and ecto-5′-nucleotidase activities with high consumption of extracellular GTP generating enhanced GDP, GMP and guanosine levels as demonstrated by HPLC, with final accumulation of the nucleoside. The transcript levels of the five TvNTPDases gene sequences were analyzed by qRT-PCR and the highest gene expressions were found for TvNTPDase 2 and 4 . The extracellular guanosine uptake was observed as 13C GTP nucleotide into parasite DNA and it was lower than that observed for adenosine, labeled as 13C ATP. These findings indicate the T. vaginalis preference for adenosine uptake and the accumulation of guanosine in the extracellular milieu, corroborating with HPLC data. Our data demonstrate, for the first time, the cascade of guanine nucleotides in T. vaginalis and open possibilities on the study of guanine-related purines other than the classical intracellular activity of G proteins for signal transduction. [ABSTRACT FROM AUTHOR]

Previous studies have shown that maternal consumption of polyphenol‐rich foods after the third trimester of pregnancy may interfere with the anatomical and functional activity of the fetal heart as, to our knowledge, there are no validated instruments to quantify total polyphenols in pregnant women. The aim of this study was evaluate the reproducibility and validity of a food frequency questionnaire (FFQ), with 52 items, to assess the intake of polyphenol‐rich foods in pregnant women in Brazil. This cross‐sectional study included 120 pregnant women who participated in nutritional interviews in two moments. The intake of polyphenols estimated by the developed FFQ was compared with the average of two 24‐h recalls (24HR), with the average intake measured by a 3‐day food diary (D3days) and with the urinary excretion of total polyphenols. The triangular method was applied to calculate Pearson's correlation coefficients, intraclass correlation and Bland–Altman plots for the FFQ, using an independent biochemical marker, in addition to classification by quarters of consumption. The questionnaires were log transformed, adjusted for body mass index and gestational age. The adjustment for energy was applied only of 24HR and D3days. Analysis of the reproducibility between the FFQ showed a very high correlation (r = 0.72; P < 0.05). A low but significant association was observed between the FFQ and urinary excretion (0.23; P = 0.01). The association between the dietary survey methods was moderate to very high (r = 0.36 to r = 0.72; P < 0.001). In conclusion, this questionnaire showed reproducibility and validity for the quantification of consumption of total polyphenols in pregnant women. [ABSTRACT FROM AUTHOR]

Many acute poisonings lack effective and specific antidotes. Due to both intentional and accidental exposures, paraquat (PQ) causes thousands of deaths annually, especially by pulmonary fibrosis. Melatonin (Mel), when incorporated into lipid-core nanocapsules (Mel-LNC), has enhanced antioxidant properties. The effects of such a formulation have not yet been studied with respect to mitigation of PQ- induced cytotoxicity and DNA damage. Here, we have tested whether Mel-LNC can ameliorate PQ-induced toxicity in the A549 alveolar epithelial cell line. Physicochemical characterization of the formulations was performed. Cellular uptake was measured using nanocapsules marked with rhodamine B. Cell viability was determined by the MTT assay and DNA damage was assessed by the comet assay. The enzyme-modified comet assay with endonuclease III (Endo III) and formamidopyrimidine glycosylase (FPG) were used to investigate oxidative DNA damage. Incubation with culture medium for 24 h did not alter the granulometric profile of Mel-LNC formulations. Following treatment (3 and 24 h), red fluorescence was detected around the cell nucleus, indicating internalization of the formulation. Melatonin solution (Mel), Mel-LNC, and LNC did not have significant effects on cell viability or DNA damage. Pre-treatment with Mel-LNC enhanced cell viability and showed a remarkable reduction in % DNA in tail compared to the PQ group; this was not observed in cells pre-treated with Mel. PQ induces oxidative DNA damage detected with the enzyme-modified comet assay. Mel-LNC reduced this damage more effectively than did Mel. In summary, Mel-LNC is better than Mel at protecting A549 cells from the cytotoxic and genotoxic effects of PQ. [ABSTRACT FROM AUTHOR]

Background Cardiovascular disease is a cause of concern in public health worldwide, reinforcing the need for studies related to the identification of potential agents that contribute to the inflammation process and atherosclerosis. This study aimed to evaluate whether metals are associated with inflammatory and kidney damage and could contribute to the atherosclerosis process. Methods Blood metals, inflammatory markers, homocysteine, antioxidants and renal markers were measured in 42 taxi drivers and 27 controls (non-occupationally exposed). Results Taxi drivers had increased Hg, As, Pb and Cd levels, however Cu and Zn levels were decreased compared to controls (p < 0.05). Hg, As and Pb levels were positively associated with pro-inflammatory cytokines, nitric oxide and negatively associated with glutathione peroxidase. Moreover, Hg, As and Pb presented positive associations with homocysteine, an independent risk factor for atherosclerosis. Regarding markers of kidney function, N-acetyl-beta- d -glucosaminidase levels were increased in taxi drivers and correlated to inflammation markers. Conclusion Hg levels were found above the recommended limits in taxi drivers and both Hg and As levels showed associations with inflammatory process, oxidative status and homocysteine. Thus, chemical substances as Hg and As can be considered as additional contributors to the development of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

There have been reports of genetic effects affecting the metabolism of Hg and Pb individually, and thus modulating their toxicities. However, there is still a knowledge gap with respect to how genetics may influence the toxicities of these toxic metals during a co-exposure scenario. This present study is therefore aimed at investigating the effects of polymorphisms in genes ( GSTM1, GSTT1, GSTP1, GCLM, GCLC, GPx1, ALAD, VDR and MDR1) that have been implicated in Hg and Pb metabolisms affects the kinetics of these metals, as well as various blood antioxidant status parameters: MDA and GSH, and the activities of CAT, GPx and ALAD among populations that have been co-exposed to both Hg and Pb. Study subjects (207 men; 188 women) were from an Amazonian population in Brazil, exposed to Hg and Pb from diet. The blood levels of Hg and Pb were determined by ICP-MS while genotyping were performed by PCR assays. The median values of Hg and Pb in blood were 39.8 µg/L and 11.0 µg/dL, respectively. GSTM1, ALAD and VDR polymorphisms influenced Hg in blood ( β =0.17; 0.37 and 0.17; respectively, p <0.050) while variations on GCLM, GSTT1 and MDR1 (TT) modulated the concentrations of Pb among the subjects ( β =−0.14; 0.13 and −0.22; re–spectively, p <0.050). GSTT1 and GCLM polymorphisms also are associated to changes of MDA concentrations. Persons with null GSTM1 genotype had higher activity of the antioxidant enzyme CAT than carries of the allele. Individuals with deletion of both GSTM1 and GSTT1 had a decreased expression of GPx compared to those that expressed at least, one of the enzymes. ALAD 1/2 subjects had lower ALAD activity than individuals with the non-variant genotype. Our findings give further support that polymorphisms related to Hg and Pb metabolism may modulate Hg and Pb body burden and, consequently metals-induced toxicity. [ABSTRACT FROM AUTHOR]

Children are especially vulnerable to adverse effects of multiple metals exposure. The aim of this study was to assess some metals concentrations such as lead (Pb), arsenic (As), chromium (Cr), manganese (Mn) and iron (Fe) in whole blood, serum, hair and drinking water samples using inductively coupled plasma-mass spectrometry (ICP-MS) in rural and urban children. In addition, evaluate the adverse effects of multiple metals exposure on cognitive function and δ-aminolevulinate dehydratase (ALA-D) activity. The cognitive ability assessment was performed by the Raven's Colored Progressive Matrices (RCPM) test. The ALA-D activity and ALA-D reactivation index (ALA-RE) activity with DTT and ZnCl 2 also were determined. Forty-six rural children and 23 urban children were enrolled in this study. Rural children showed percentile IQ scores in the RCPM test significantly decreased in relation to urban children. According to multiple linear regression analysis, the Mn and Fe in hair may account for the cognitive deficits of children. Manganese and Fe in hair also were positively correlated with Mn and Fe in drinking water, respectively. These results suggest that drinking water is possibly a source of metals exposure in children. ALA-D activity was decreased and ALA-RE with DTT and ZnCl 2 was increased in rural children in comparison to urban children. Moreover, ALA-D inhibition was correlated with Cr blood levels and ALA-RE/DDT and ALA-RE/ZnCl 2 were correlated with levels of Cr and Hg in blood. Thus, our results indicated some adverse effects of children's exposure to multiple metals, such as cognitive deficits and ALA-D inhibition, mainly associated to Mn, Fe, Cr and Hg. [ABSTRACT FROM AUTHOR]

Gas station attendants and taxi drivers are occupationally exposed to xenobiotics which may be harmful to their health. Atmospheric pollutants and benzene can lead to DNA damage. Genotoxicity and mutagenicity assays can be used to evaluate the effects of these pollutants. We have evaluated genotoxicity and mutagenicity in workers occupationally exposed to xenobiotics, by application of the 8-hydroxy-2-deoxyguanosine (8-OHdG), comet, and micronucleus (MN) assays. Biomarkers of benzene and carbon monoxyde exposure were also measured: urinary t,t-muconic acid (t,t-MA) and carboxyhaemoglobin (COHb) in whole blood, respectively. The study groups comprised 43 gas station attendants (GSA), 34 taxi drivers (TD), and 22 persons without known occupational exposures (NE). Levels of t,t-MA in the GSA group were significantly elevated compared to the NE group (p<0.001), however these levels were below of levels established by ACGIH (American Conference of Governmental Industrial Hygienists). COHb levels were not significantly different between the TD and NE groups (p>0.05). DNA damage index (DI) and 8-OHdG levels were significantly higher for both the GSA and TD groups, compared to the NE group (p<0.001), but MN frequencies were not elevated. Spearman correlation analysis showed that the frequency of MN was positively correlated with 8-OHdG. A positive correlation between DNA DI levels and 8-OHdG was also observed. In conclusion, our results indicated that low levels of occupational exposure to benzene and atmospheric pollutants may be linked to genotoxicity and oxidative DNA damage. [ABSTRACT FROM AUTHOR]

Abstract: Consistent evidence has indicated that the exposure to environmental air pollution increases the risk of cardiovascular disease. This study aimed to evaluate the possible effects of occupational exposure to air pollution, especially to polycyclic aromatic hydrocarbons (PAHs), and the influence of co-morbidities on the atherosclerotic process and inflammation. For that, biomarkers of exposure such as 1-hydroxypyrene urinary, oxidative damage and markers of cardiovascular risk were determined in plasma, serum and blood. In addition, inflammation models such as carotid intima-media thickness and serum inflammatory cytokines were analyzed in 58 taxi drivers with and without co-morbidity. The results demonstrated that considering only taxi drivers without co-morbidities, 15% presented carotid intima-media thickness above reference values. For the first time it has been demonstrated that urinary 1-hydroxypyrene levels were associated with carotid intima-media thickness and with serum homocysteine levels. The multiple linear regression analysis showed that several factors may contribute to the increased carotid intima-media thickness, among which age, interleukin-6, fibrinogen and exposure to PAHs stand out. In summary, our results suggest that chronic occupational exposure to atmospheric pollution could be an additional contributor to the atherogenesis process, leading to impaired vascular health. Moreover, carotid intima-media thickness, serum homocysteine levels, fibrinogen and the total cholesterol/HDL-c ratio could be suggested as preventive measures to monitor drivers’ health. [Copyright &y& Elsevier]

Benzo[a]pyrene (BaP) is an environmental contaminant produced during incomplete combustion of organic material that is well known as a mutagenic and carcinogenic toxin. There are few studies addressing the molecular and cellular basis of behavioural alterations related to BaP exposure. The aim of this study was to evaluate the effect of subchronic oral administration of BaP on behavioral and neurochemical parameters. Wistar male rats received BaP (2 mg/kg) or corn oil (control), once a day for 28 days (n = 12/group). Spontaneous locomotor activity and short- and long-term memories were evaluated. Glial fibrillary acid protein and S100B content in the hippocampus, serum and CSF were measured using ELISA and total and phosphorylated forms of mitogen activated protein kinases (MAPKs) named extracellular signal-regulated kinases 1 and 2, p38 and c-Jun amino-terminal kinases 1 and 2, in the hippocampus, were evaluated by western blotting. BaP induced a significant increase on locomotor activity and a decrease in short-term memory. S100B content was increased significantly in cerebrospinal fluid. BaP induced a decrease on ERK2 phosphorylation in the hippocampus. Thus, BaP subchronic treatment induces an astroglial response and impairs both motor and cognitive behavior, with parallel inhibition of ERK2, a signaling enzyme involved in the hippocampal neuroplasticity. All these effects suggest that BaP neurotoxicity is a concern for environmental pollution. [ABSTRACT FROM AUTHOR]