Sintocalmy, a Passiflora incarnata Based Herbal, Attenuates Morphine Withdrawal in Mice.

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.

Piperazine designer drugs elicit toxicity in the alternative in vivo model Caenorhabditis elegans.

Piperazine designer drugs are a group of synthetic drugs of abuse that have appeared on the illicit market since the second half of the 1990s. The most common derivatives are 1-benzylpiperazine (BZP), 1-(4-methoxyphenyl)piperazine (MeOPP) and 1-(3,4-methylenedioxybenzyl)piperazine (MDBP). They can be consumed as capsules, tablets, but also in powder or liquid forms. Generally, although less potent than amphetamines, piperazines have dopaminergic and serotonergic activities. The aim of this work was to evaluate the toxic effects of BZP, MeOPP and MDBP using Caenorhabditis elegans as in vivo model for acute toxicity, development, reproduction and behavior testing. The LC50 for BZP, MeOPP and MDBP were 52.21, 5.72 and 1.22 mm, respectively. All concentrations induced a significant decrease in the body surface of the worms, indicating developmental alterations, and decrease in the brood size. Worms exposed to piperazine designer drugs also presented a decrease in locomotor activity and mechanical sensitivity, suggesting the possible dysfunction of the nervous system. Neuronal damage was confirmed through the decrease in fluorescence of BY200 strains, indicating loss of dopaminergic transporters. In conclusion, we suggest that piperazine designer drugs lead to neuronal damage, which might be the underlying cause of the altered behavior observed in humans.

In vitro toxicity assessment of rivaroxaban degradation products and kinetic evaluation to decay process.

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.

Energy drink and alcohol combination leads to kidney and liver alterations in rats.

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-ß-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.

Exposure to environment chemicals and its possible role in endocrine disruption of children from a rural area.

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.

Cognitive deficits and ALA-D-inhibition in children exposed to multiple metals.

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 ZnCl2 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 ZnCl2 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/ZnCl2 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.

Early hematological and immunological alterations in gasoline station attendants exposed to benzene.

INTRODUCTION: Elucidation of effective biomarkers may provide tools for the early detection of biological alterations caused by benzene exposure and may contribute to the reduction of occupational diseases. This study aimed to assess early alterations on hematological and immunological systems of workers exposed to benzene. METHODS: Sixty gasoline station attendants (GSA group) and 28 control subjects were evaluated. Environmental and biological monitoring of benzene exposure was performed in blood and urine. The potential effect biomarkers evaluated were δ-aminolevulinate dehydratase (ALA-D) activity, CD80 and CD86 expression in lymphocytes and monocytes, and serum interleukin-8 (IL-8). The influence of confounding factors and toluene co-exposure were considered. RESULTS: Although exposures were below ACGIH (American Conference of Governmental Industrial Hygienists) limits, reduced ALA-D activity, decreased CD80 and CD86 expression in monocytes and increased IL-8 levels were found in the GSA group compared to the control subjects. Furthermore, according to multiple linear regression analysis, benzene exposure was associated to a decrease in CD80 and CD86 expression in monocytes. CONCLUSIONS: These findings suggest, for the first time, a potential effect of benzene exposure on ALA-D activity, CD80 and CD86 expression, IL-8 levels, which could be suggested as potential markers for the early detection of benzene-induced alterations.

Atherosclerotic process in taxi drivers occupationally exposed to air pollution and co-morbidities.

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.

Nitric oxide and reactive species are modulated in the polyphenol-induced ductus arteriosus constriction in pregnant sheep.

OBJECTIVE: Because we have previously demonstrated the relation between polyphenol-rich foods (PRF) consumption and ductus arteriosus constriction, in this work, pregnant sheep were submitted to oral PRF intake for 14 days to understand how this process occurs. Fetal Doppler echocardiography, oxidative and inflammatory biomarkers and total polyphenol excretion were evaluated. RESULTS: The high polyphenol intake induced ductus arteriosus constriction by 71.6% increase in systolic (P = 0.001) and 57.8% in diastolic velocities (P = 0.002), and 18.9% decrease in pulsatility index (P = 0.033), along with 1.7-fold increase in total polyphenol excretion, 2.3-fold decrease in inflammatory mediator nitric oxide and following redox status changes (mean ± standard deviation): higher protein carbonyls (1.09 ± 0.09 and 1.49 ± 0.31), catalase (0.69 ± 0.39 and 1.44 ± 0.33) and glutathione peroxidase (37.23 ± 11.19 and 62.96 ± 15.03) in addition to lower lipid damage (17.22 ± 2.05 and 12.53 ± 2.11) and nonprotein thiols (0.11 ± 0.04 and 0.04 ± 0.01) found before and after treatment, respectively. Ductal parameters correlated to NOx , catalase, glutathione peroxidase and protein carbonyl. CONCLUSION: Our results highlight the need to reduce maternal PRF intake in late pregnancy to prevent fetal duct constriction through NO-mediated vasoconstrictive action of polyphenols.

Methionine stimulates motor impairment and cerebellar mercury deposition in methylmercury-exposed mice.

Methylmercury (MeHg) is a highly toxic environmental contaminant that produces neurological and developmental impairments in animals and humans. Although its neurotoxic properties have been widely reported, the molecular mechanisms by which MeHg enters the cells and exerts toxicity are not yet completely understood. Taking into account that MeHg is found mostly bound to sulfhydryl-containing molecules such as cysteine in the environment and based on the fact that the MeHg-cysteine complex (MeHg-S-Cys) can be transported via the L-type neutral amino acid carrier transport (LAT) system, the potential beneficial effects of L-methionine (L-Met, a well known LAT substrate) against MeHg (administrated as MeHg-S-Cys)-induced neurotoxicity in mice were investigated. Mice were exposed to MeHg (daily subcutaneous injections of MeHg-S-Cys, 10 mg Hg/kg) and/or L-Met (daily intraperitoneal injections, 250 mg/kg) for 10 consecutive days. After treatments, the measured hallmarks of toxicity were mostly based on behavioral parameters related to motor performance, as well as biochemical parameters related to the cerebellar antioxidant glutathione (GSH) system. MeHg significantly decreased motor activity (open-field test) and impaired motor performance (rota-rod task) compared with controls, as well as producing disturbances in the cerebellar antioxidant GSH system. Interestingly, L-Met administration did not protect against MeHg-induced behavioral and cerebellar changes, but rather increased motor impairments in animals exposed to MeHg. In agreement with this observation, cerebellar levels of mercury (Hg) were higher in animals exposed to MeHg plus L-Met compared to those only exposed to MeHg. However, this event was not observed in kidney and liver. These results are the first to demonstrate that L-Met enhances cerebellar deposition of Hg in mice exposed to MeHg and that this higher deposition may be responsible for the greater motor impairment observed in mice simultaneously exposed to MeHg and L-Met.

Exogenous and endogenous antioxidants attenuate the lipid peroxidation in workers occupationally exposed to paints.

Occupational exposure to organic solvents present in paints is responsible for an increased production of reactive species, thus enabling the development of several diseases. Besides, both exo- and endogenous antioxidant defense systems are necessary to avoid oxidative tissue damage. This study investigated possible protective effects of the exo- and endogenous antioxidants on oxidative damage in painters occupationally exposed to organic solvents (n = 42) and controls (n = 28). Retinol, lycopene and ß-carotene were significantly lower in the exposed group. Despite the fact that blood toluene was below the biological exposure limits, malondialdehyde levels and antioxidant enzyme activities were increased, whereas reduced glutathione levels were decreased in painters, compared to nonexposed subjects. Moreover, multivariate regression models showed that reduced glutathione and carotenoids (mainly ß-carotene) have the major influence on lipid peroxidation (LPO). The present work suggests that the exogenous antioxidants, such as carotenoids, could protect occupationally exposed subjects to xenobiotics from LPO.

Genotoxicity and oxidative stress in gasoline station attendants.

We evaluated genotoxic effects of exposure to low levels of benzene, a class I human carcinogen, among gasoline station attendants (GSA). Oxidative stress and the protective effects of antioxidants on DNA damage were also analyzed. Although exposures were below ACGIH (American Conference of Governmental Industrial Hygienists) limits, the GSA group presented higher DNA damage indices and micronucleus frequencies, increased oxidative protein damage, and decreased antioxidant capacity relative to the control group. Duration of benzene exposure was correlated with DNA and protein damage. The biomarkers evaluated in this work may provide early signals of damage in subjects occupationally exposed to benzene.

Blood thioredoxin reductase activity, oxidative stress and hematological parameters in painters and battery workers: relationship with lead and cadmium levels in blood.

Oxidative stress has been shown to be involved in lead and cadmium toxicity. We recently showed that the activity of the antioxidant enzyme thioredoxin reductase (TrxR) is increased in the kidneys of lead-exposed rats. The present study evaluated the blood cadmium and blood lead levels (BLLs) and their relationship with hematological and oxidative stress parameters, including blood TrxR activity in 50 painters, 23 battery workers and 36 control subjects. Erythrocyte δ-aminolevulinate dehydratase (δ-ALA-D) activity and its reactivation index were measured as biomarkers of lead effects. BLLs increased in painters, but were even higher in the battery workers group. In turn, blood cadmium levels increased only in the painters group, whose levels were higher than the recommended limit. δ-ALA-D activity was inhibited only in battery workers, whereas the δ-ALA-D reactivation index increased in both exposed groups; both parameters were correlated to BLLs (r = -0.59 and 0.84, P < 0.05), whereas the reactivation index was also correlated to blood cadmium levels (r = 0.27, P < 0.05). The changes in oxidative stress and hematological parameters were distinctively associated with either BLLs or blood cadmium levels, except glutathione-S-transferase activity, which was correlated with both lead (r = 0.34) and cadmium (r = 0.47; P < 0.05). However, TrxR activity did not correlate with any of the metals evaluated. In conclusion, blood TrxR activity does not seem to be a good parameter to evaluate oxidative stress in lead- and cadmium-exposed populations. However, lead-associated changes in biochemical and hematological parameters at low BLLs underlie the necessity of re-evaluating the recommended health-based limits in occupational exposure to this metal.

Evaluation of genotoxicity and oxidative damage in painters exposed to low levels of toluene.

Toluene is an organic solvent used in numerous processes and products, including industrial paints. Toluene neurotoxicity and reproductive toxicity are well recognized; however, its genotoxicity is still under discussion, and toluene is not classified as a carcinogenic solvent. Using the comet assay and the micronucleus test for detection of possible genotoxic effects of toluene, we monitored industrial painters from Rio Grande do Sul, Brazil. The putative involvement of oxidative stress in genetic damage and the influences of age, smoking, alcohol consumption, and exposure time were also assessed. Although all biomarkers of toluene exposure were below the biological exposure limits, painters presented significantly higher DNA damage (comet assay) than the control group; however, in the micronucleus assay, no significant difference was observed. Painters also showed alterations in hepatic enzymes and albumin levels, as well as oxidative damage, suggesting the involvement of oxidative stress. According to multiple linear regression analysis, blood toluene levels may account for the increased DNA damage in painters. In summary, this study showed that low levels of toluene exposure can cause genetic damage, and this is related to oxidative stress, age, and time of exposure.

Fetal ductal constriction caused by maternal ingestion of green tea in late pregnancy: an experimental study.

OBJECTIVES: The aim of this study was to test the hypothesis that experimental maternal intake of green tea in late pregnancy causes fetal ductus arteriosus constriction, probably because of prostaglandin inhibition. METHODS AND RESULTS: Twelve fetal lambs (pregnancy > 120 days) were assessed before and after maternal administration of green tea (n = 8) or water (n = 4; controls) as the only source of liquid. After 1 week, echocardiography showed signs of constriction of the ductus arteriosus in all fetuses from mothers ingesting green tea, with increase in mean systolic velocity(from 0.70 ± 0.19 m/s to 0.92 ± 0.15 m/s, 31.4%, p = 0.001) and mean diastolic velocity (0.19 ± 0.05 m/s to 0.31 ± 0.01 m/s, 63.1%, p < 0.001), decrease of pulsatility index (2.2 ± 0.4 to 1.8 ± 0.3, 22.2%, p = 0.003) and increase of mean right ventricular/left ventricular diameter ratio (0.89 ± 0.14 to 1.43 ± 0.23, 60.6%, p < 0.001). In the four control fetuses, there were no significant changes. All lambs exposed to green tea also showed at autopsy dilated and hypertrophic right ventricles, which was not present in control fetuses. Histological analysis showed a significantly larger mean thickness of the medial avascular zone of the ductus arteriosus in fetuses exposed to green tea than in controls (747.6 ± 214.6 µm vs 255.3 ± 97.9 µm, p < 0.001). CONCLUSIONS: This study in fetal lambs shows a cause and effect relationship between experimental maternal exposure of green tea and fetal ductus arteriosus constriction in late pregnancy.

Plasma malondialdehyde levels and risk factors for the development of chronic complications in type 2 diabetic patients on insulin therapy.

BACKGROUND: We assessed plasma malondialdehyde (MDA) levels as a biomarker of lipid peroxidation in type 2 diabetic patients on insulin therapy. Associations among MDA levels and some risk factors for the development of chronic complications of diabetes were also evaluated. METHODS: MDA, fasting glucose, fructosamine, urinary albumin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, creatinine, uric acid, serum albumin, lactate, high sensitive C reactive protein (hsCRP), and vitamin E were measured in 53 type 2 diabetic patients and 26 healthy subjects. RESULTS: MDA levels were higher in type 2 diabetes insulin users (12.8 +/- 3.0 micromol/L) and type 2 diabetes no insulin users (10.3 +/- 2.1 micromol/L) compared to control subjects (8.2 +/- 2.1 micromol/L). Fasting glucose, fructosamine, urinary albumin, and hsCRP were higher in all type 2 diabetic patients compared to controls. Significant correlations were observed between MDA and fasting glucose (r = 0.685, p < 0.001), fructosamine (r = 0.526, p < 0.001), urinary albumin (r = 0.516, p < 0.001), and the duration of type 2 diabetes (r = 0.401, p = 0.005). CONCLUSIONS: MDA levels increased in type 2 diabetes, especially in patients on insulin therapy. Chronic hyperglycemia and other biomarkers, such as urinary albumin, were correlated with MDA levels, suggesting the involvement of lipid peroxidation in the pathogenesis of diabetes complications.

Chemobrain in Breast Cancer: Mechanisms, Clinical Manifestations, and Potential Interventions.

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.

Toxicity of pesticides widely applied on soybean cultivation: Synergistic effects of fipronil, glyphosate and imidacloprid in HepG2 cells.

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 EC50 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 EC50 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.

Brazilian workers occupationally exposed to different toxic agents: A systematic review on DNA damage.

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.

N-acetylcysteine on oxidative damage in diabetic rats.

N-acetylcysteine (NAC) is a potent mucolitic agent and also an antioxidant. Its antioxidant action is due to its ability to stimulate reduced glutathione (GSH) synthesis, therefore maintaining intracellular levels. The aim of this study was to evaluate the effects of NAC administered intraperitoneally (i.p.) in a decreasing of oxidative tissue damage in the liver and kidney of alloxan-induced diabetic rats, especially on thiolic groups (nonproteic and proteic groups). Adult male Wistar rats (200-350 g) were used; diabetes was induced accordingly by a single i.p. injection of alloxan monohydrate, and the control group received a similar volume of the vehicle. Lipid peroxidation (LPO) biomarker (malondialdehyde; MDA), δ-ALA-D activity, GSH, superoxide dismutase (SOD), and glutathione peroxidase (GPx) were quantified to assess the oxidative stress. All tests were performed in tissue homogenates. Creatinine, urea, aspartate transaminase, and alanine transaminase were determined by commercial kits, using serum samples. A significant decrease in LPO (i.e., hepatic and renal) and an increase in δ-aminolevulinate dehydratase activity, especially in the renal tissue, were observed. Also, NAC at 75 mg/kg showed more effective restoration of oxidative stress biomarkers than NAC at 25 mg/kg. Our findings suggest that NAC can be used as an antioxidant agent in diabetes, exhibiting modulatory action on the oxidative stress biomarkers analyzed in this work. Moreover, these findings can contribute to others' research, regarding the utilization of NAC to ALA-D activity restoration in the kidneys.