The Influence of Blood Titanium Levels on DNA Damage in Brazilian Workers Occupationally Exposed to Different Chemical Agents.

Occupational exposure to pollutants may cause health-damaging effects in humans. Genotoxicity assays can be used to detect the toxic effects of pollutants. In the present study, we evaluated genetic damage in three populations occupationally exposed to benzene, pyrenes, and agrochemicals and assessed the possible influence of titanium (Ti) co-exposure.

LaSOM 335, active against bladder cancer cells, interferes with Let-60 (hRas) and reduces CD73 expression/activity.

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.

Antiproliferative activity and toxicity evaluation of 1,2,3-triazole and 4-methyl coumarin hybrids in the MCF7 breast cancer cell line.

Four coumarin-triazole hybrids were selected from our in house library and screened for cytotoxic activity on A549 (lung cancer), HepG2 (liver cancer), J774A1 (mouse sarcoma macrophage), MCF7 (breast cancer), OVACAR (ovarian cancer), RAW (murine leukaemia macrophage), and SiHa (uterus carcinoma) and their toxicity was assessed on 3T3 (healthy fibroblasts) cell lines. SwissADME pharmacokinetic prediction was performed. Effects on ROS production, mitochondrial membrane potential, apoptosis/necrosis and DNA damage were evaluated.

DoE development of ionic gradient liposomes: A successful approach to improve encapsulation, prolong anesthesia and decrease the toxicity of etidocaine.

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, a formulation optimized by Design of Experiments, composed of hydrogenated soy phosphatidylcholine:cholesterol:EDC, and characterized by DLS, NTA, TEM/Cryo-TEM, DSC and H NMR.

Acute Toxicity Evaluation of Phosphatidylcholine Nanoliposomes Containing Nisin in .

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.

Characterization and in vivo toxicological evaluation of multi-walled carbon nanotubes: a low-dose repeated intratracheal administration study.

This study characterized and investigated the toxicity of two multi-walled carbon nanotubes (MWCNT) NM-401 and NM-403 at 60 and 180 µg after four repeated intratracheal instillations; follow-up times were 3, 7, 30, and 90 days after the last instillation. NM-401 was needle-like, long, and thick, while NM-403 was entangled, short, and thin. Both MWCNT types induced transient pulmonary and systemic alterations in renal function and oxidative lipid damage markers in recent times.

The Role of Alternative Toxicological Trials in Drug Discovery Programs. The Case of and Other Methods.

The discovery of a new drug requires over a billion dollars and around 12 years of research efforts, and toxicity is the leading reason for the failure to approve candidate drugs. Many alternative methods have been validated to detect toxicity as early as possible to diminish the waste of resources and efforts in medicinal chemistry research, and in vivo alternative methods are especially valuable for the amount of information they can provide at little cost and in a short time. In this work, we present a review of the literature published between the years 2000 and 2021 on in vivo alternative methods of toxicity screening employed in medicinal chemistry, which we believe will be useful because, in addition to shortening the research time, these studies provide much additional information aside from the toxicity of drug candidate compounds.

Children Environmentally Exposed to Agrochemicals in Rural Areas Present Changes in Oxidative Status and DNA Damage.

Rural children are exposed to several chemicals. This study evaluated the environmental co-exposure of rural children to cholinesterase inhibitor insecticides and metals/metalloids, and the resulting oxidative stress and DNA damage. Seventy-two children (5 to 16 years old) were studied at two different moments: period 1, when agrochemicals were less used, and period 2, when agrochemicals were extensively used in agriculture.

Oxidative damage, inflammation, genotoxic effect, and global DNA methylation caused by inhalation of formaldehyde and the purpose of melatonin.

Formaldehyde (FA) exposure has been proven to increase the risk of asthma and cancer. This study aimed to evaluate for 28 days the FA inhalation effects on oxidative stress, inflammation process, genotoxicity, and global DNA methylation in mice as well as to investigate the potential protective effects of melatonin. For that, analyses were performed on lung, liver and kidney tissues, blood, and bone marrow.

Cellular response to chemicals present in air pollution in occupationally exposed workers and its potential cancer susceptibility.

The study aimed to evaluate the potential effects of the chronic exposure to chemical agents from air pollution on phenotypic and genotypic expressions of peripheral biomarkers and tumor-related proteins in mononuclear cells. This study evaluates 85 taxi drivers (outdoor workers) and 55 non-occupationally exposed persons (NOE) to air pollution (indoor workers). The biomarkers were urinary 1-hydroxypyrene (1-OHP), for organic agents, and blood As and Ni, for inorganic agents.

Ochratoxin A presence in Cabernet Sauvignon wine changes antioxidant activity and oxidative stress markers .

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.

New pharmacological findings linked to biphenyl DHPMs, kinesin Eg5 ligands: anticancer and antioxidant effects.

Dihydropyrimidin-2-thiones (DHPMs) are a class of heterocyclic compound which have been intensively investigated mainly due to their anticancer activity as kinesin Eg5 inhibitors. A library of N1 aryl substituted DHPMs were tested against glioma and bladder cancer cell lines. Quantitative structure-activity relationship (QSAR) investigation was performed in order to identify key elements of DHPMs linked with their antiproliferative effect.

Biochemical, hematological and immunological parameters and relationship with occupational exposure to pesticides and metals.

This study aimed to evaluate biomarkers of exposure to cholinesterase inhibitors insecticides (AChE and BuChE activities) and metals (As, Cd, Cr, Mn, Ni, and Pb blood levels) and their associations with biochemical, hematological, and immunological parameters in farmers from Southern Brazil. One hundred and sixteen individuals were divided into two groups: 62 farmers (exposed group) and 54 subjects non-occupationally exposed (NOE) to agrochemicals. Erythrocyte (AChE) and serum (BuChE) cholinesterases activities were significantly reduced as well as blood Cd and Pb levels were increased in farmers when compared to NOE group (p < 0.

Occupational risk assessment of exposure to metals in chrome plating workers.

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.

Novel coumarins active against Trypanosoma cruzi and toxicity assessment using the animal model Caenorhabditis elegans.

Background: Chagas disease (CD) is a tropical parasitic disease. Although the number of people infected is very high, the only drugs available to treat CD, nifurtimox (Nfx) and benznidazole, are highly toxic, particularly in the chronic stage of the disease. Coumarins are a large class of compounds that display a wide range of interesting biological properties, such as antiparasitic.

Evaluation of immunological, inflammatory, and oxidative stress biomarkers in gasoline station attendants.

Background: Gasoline is a complex mixture of saturated and unsaturated hydrocarbons, in which aromatic compounds, such as BTX (benzene, toluene, and xylene) feature as the main constituents. Simultaneous exposure to these aromatic hydrocarbons causes a significant impact on benzene toxicity. In order to detect early alterations caused in gasoline station attendants exposed to BTX compounds, immunological, inflammatory, and oxidative stress biomarkers were evaluated.

Melatonin-loaded lipid-core nanocapsules protect against lipid peroxidation caused by paraquat through increased SOD expression in Caenorhabditis elegans.

Background: Melatonin has been described in the literature as a potent antioxidant. However, melatonin presents variable, low bioavailability and a short half-life. The use of polymeric nanoparticulated systems has been proposed for controlled release.

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.

In vitro cardiotoxicity evaluation of graphene oxide.

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.

Inflammatory and oxidative stress biomarkers at protein and molecular levels in workers occupationally exposed to crystalline silica.

Workers chronically exposed to respirable crystalline silica (CS) are susceptible to adverse health effects like silicosis and lung cancer. This study aimed to investigate potential early peripheral biomarkers of inflammation and oxidative stress in miners. The subjects enrolled in this study were occupationally unexposed workers (OUW, n = 29) and workers exposed to crystalline silica (WECS), composed by miners, which were divided into two subgroups: workers without silicosis (WECS I, n = 39) and workers diagnosed with silicosis, retired from work (WECS II, n = 42).

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.

Effect of N-1 arylation of monastrol on kinesin Eg5 inhibition in glioma cell lines.

An original and focused library of two sets of dihydropyrimidin-2-thiones (DHPMs) substituted with N-1 aryl groups derived from monastrol was designed and synthesized in order to discover a more effective Eg5 ligand than the template. Based on molecular docking studies, four ligands were selected to perform pharmacological investigations against two glioma cell lines. The results led to the discovery of two original compounds, called and , with an anti-proliferative effects, achieving IC values of about half that of the IC of monastrol in both cell lines.

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.

The role of B7 costimulation in benzene immunotoxicity and its potential association with cancer risk.

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.

Inflammatory and oxidative stress parameters as potential early biomarkers for silicosis.

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.