Exploring Toxicity of Per- and Polyfluoroalkyl Substances (PFAS) Mixture Through ADMET and Toxicogenomic In Silico Analysis: Molecular Insights.

This study aimed to explore the health impacts, mechanisms of toxicity, and key gene biomarkers of a mixture of the most prominent perfluoroalkyl/polyfluoroalkyl substances (PFAS) through in silico ADMET and toxicogenomic analysis. The following databases and tools were used: AdmetSAR (2.0), ADMETlab (2.

In silico attempt to reveal the link between cancer development and combined exposure to the maize herbicides: Glyphosate, nicosulfuron, S-metolachlor and terbuthylazine.

Pesticides are crucial for crop protection and have seen a 50 % increase in use in the last decade. Besides preventing significant crop losses their use has raised health concerns due to consumer exposure through residues in food and water. The toxicity data from individual components is often used to assess overall mixture toxicity, but uncertainty persists in understanding the behaviors of individual chemicals within these mixtures.

analysis of the impact of toxic metals on COVID-19 complications: molecular insights.

COVID-19 can cause a range of complications, including cardiovascular, renal, and/or respiratory insufficiencies, yet little is known of its potential effects in persons exposed to toxic metals. The aim of this study was to answer this question with toxicogenomic methods that can provide molecular insights into COVID-19 complications owed to exposure to arsenic, cadmium, lead, mercury, nickel, and chromium. For this purpose we relied on the Comparative Toxicogenomic Database (CTD), GeneMANIA, and ToppGene Suite portal and identified a set of five common genes () for the six metals and COVID-19, all of which code for pro-inflammatory and anti-inflammatory cytokines.

Thyroid under siege: Unravelling the toxic impact of real-life metal mixture exposures in Wistar rats.

This study explored the effect of a toxic metal(oid) mixture (cadmium, lead, arsenic, mercury, chromium, and nickel) on thyroid function in Wistar rats exposed for 28 or 90 days. Dose levels were determined based on prior human-biomonitoring investigation. The experiment included control (male/female rats, 28 and 90 days) and treated groups, reflecting the lower confidence limit of the Benchmark Dose (BMDL) for hormone levels (M1/F1, 28 and 90 days), median concentrations (M2/F2, 28 and 90 days), 95th percentile concentrations (M3/F3, 28 and 90 days) measured in a human study, and reference values for individual metals extracted from the literature (M4/F4, 28 days only).

Integrative investigation of hematotoxic effects induced by low doses of lead, cadmium, mercury and arsenic mixture: In vivo and in silico approach.

The effect of the lead (Pb), cadmium (Cd), mercury (Hg) and arsenic (As) mixture (MIX) on hematotoxicity development was investigated trough combined approach. In vivo subacute study (28 days) was performed on rats (5 per group): a control group and five groups orally exposed to increasing metal(loid) mixture doses, MIX 1- MIX 5 (mg/kg bw./day) (Pb: 0.

Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach.

Metals exert detrimental effects on various systems within the body, including the nervous system. Nevertheless, the dose-response relationship concerning the administration of low doses of metal mixtures remains inadequately explored. The assessment of neurotoxic effects of lead, cadmium, mercury, and arsenic mixture (MIX) administered at low dose ranges, was conducted using an in vivo approach.

Increased oxidative stress in shoe industry workers with low-level exposure to a mixture of volatile organic compounds.

This study aimed to assess the redox status and trace metal levels in 49 shoe industry workers (11 men and 38 women) occupationally exposed to a mixture of volatile organic compounds (VOCs), which includes aliphatic hydrocarbons, aromatic hydrocarbons, ketones, esters, ethers, and carboxylic acids. All measured VOCs were below the permitted occupational exposure limits. The control group included 50 unexposed participants (25 men and 25 women).

Sulforaphane-A Compound with Potential Health Benefits for Disease Prevention and Treatment: Insights from Pharmacological and Toxicological Experimental Studies.

Sulforaphane (SFN), which is a hydrolysis product from glucoraphanin, a compound found in cruciferous vegetables, has been studied for its potential health benefits, particularly in disease prevention and treatment. SFN has proven to be effective in combating different types of cancer by inhibiting the proliferation of tumors and triggering apoptosis. This dual action has been demonstrated to result in a reduction in tumor size and an enhancement of survival rates in animal models.

Endocrine disruptors in e-waste dismantling dust: In silico prediction of mixture-induced reproductive toxicity mechanisms.

The constant exposure of humans to a mixture of low doses of toxic substances, emerging from the daily emission of toxic dust containing various metals and organic compounds in electrical and electronic waste (e-waste) recycling areas, poses potential harmful effects on health and the environment. While individually recognized as endocrine disruptors affecting hormonal balance, the combined impact of these toxic substances in a mixture remains insufficiently explored, particularly in relation to reproductive health. Thus, the aim of this in silico analysis was to: (i) assess the relationship between the exposure to a mixture of DBDE, DBDPE, TBBPA, Pb, Cd and Ni and development of male and female reproductive system disorders; and (ii) demonstrate the ability of in silico toxicogenomic tools in revealing the potential molecular mechanisms involved in the mixture toxicity.

Nickel as a potential disruptor of thyroid function: benchmark modelling of human data.

Introduction: Nickel (Ni) is one of the well-known toxic metals found in the environment. However, its influence on thyroid function is not explored enough. Hence, the aim of this study was to analyse the potential of Ni to disrupt thyroid function by exploring the relationship between blood Ni concentration and serum hormone levels (TSH, T4, T3, fT4 and fT3), as well as the parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) by using correlation analysis and Benchmark (BMD) concept.

Involvement of toxic metals and PCBs mixture in the thyroid and male reproductive toxicity: In silico toxicogenomic data mining.

Toxicological research is mostly limited to considering the effects of a single substance, even though the real exposure of people is reflected in their daily exposure to many different chemical substances in low-doses. This in silico toxicogenomic study aims to provide evidence for the selected environmental (organo)metals (lead, cadmium, methyl mercury) + polychlorinated biphenyls mixture involvement in the possible alteration of thyroid, and male reproductive system function, and furthermore to predict the possible toxic mechanisms of the environmental cocktail. The Comparative Toxicogenomic Database, GeneMANIA online software, and ToppGene Suite portal were used as the main tools for toxicogenomic data mining and gene ontology analysis.

In vivo and in silico approach in revealing the influence of lead (Pb) on thyroid gland function.

The purpose of this study was to examine the impact of low doses of lead (Pb) on levels of thyroid hormones (T3, T4, FT3, and FT4) and thyroid-related antibodies (anti-Tg and anti-TPO) in the rat model, as well as genes that are related to Pb and thyroid function, relationships between genes, biological processes, molecular processes, and pathways using an in silico approach. Male rats were randomized into seven groups (n = 42), one control group and six groups that received a range of Pb doses: 0.1, 0.

Effects of the real-life metal(oid)s mixture on female reproductive function: Less is different.

The current study aimed to examine the effect of toxic metal(oid) mixtures (lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), cadmium (Cd), chromium (Cr), and nickel (Ni)) on female reproductive function in Wistar rats after the 28- and 90-day exposure to dose levels calculated on the basis of the previously conducted human study. Experimental groups included: 2 controls (28- and 90-day), treated groups - doses based on: median- F2 (28) and F2(90) and 95th percentile concentrations in the general human population - F3(28) and F3(90); calculated lower Benchmark dose confidence limit (BMDL) for effects on hormone levels - F1(28) and F1(90) and a group given the doses calculated on the basis of the reference values from the literature (F4(28)). Blood and ovarian samples were collected for sex hormones and ovary redox status analysis.

Cadmium and lead implication in testis cancer; is there a connection?

Testis cancer (TC) is the most common malignancy of young men. Current evidence from studies, alongside genetics and hormonal status, suggests a significant role of toxic metals, cadmium (Cd) and lead (Pb), in the origin and development of TC. Besides oxidative stress and endocrine disruption, interaction with bioelements is one of the critical mechanisms of Cd and Pb toxicity and malign transformation.

Testing sulforaphane as a strategy against toxic chemicals of public health concern by toxicogenomic data analysis: Friend or foe at the gene level - Colorectal carcinoma case study.

Toxic metals (cadmium (Cd), lead (Pb), mercury (Hg) and arsenic (As)) and plastificators (bis (2 - ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP)) and bisphenol A (BPA)) have been suggested to aid in colorectal carcinoma (CRC) advancement. Sulforaphane (SFN), isothiocyanate from cruciferous vegetables, diminishes chemical carcinogenesis susceptibility, but has been shown to act as a friend or a foe depending on various factors. By conducting the mechanistic toxicogenomic data mining approach, this research aimed to determine if SFN can alleviate toxic-metal and/or phthalate/BPA mixture-induced CRC at the gene level.

Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats.

Recent data indicate that lead (Pb) can induce adverse effects even at low exposure levels. Moreover, the corresponding mechanisms of low Pb toxicity have not been well identified. In the liver and the kidneys, Pb was found to induce various toxic mechanisms leading to organ physiological disruption.

In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether.

The current study aimed to assess the connection between the mixture of lead (Pb), cadmium (Cd), arsenic (As), methylmercury (MeHg) and decabrominated diphenyl ether (decaBDE) and thyroid function, by using in silico toxicogenomic data-mining approach. To obtain the linkage between investigated toxic mixture and thyroid diseases (TDs), the Comparative Toxicogenomics Database (CTD) was used, while gene ontology (GO) enrichment analysis was performed by ToppGeneSuite portal. The analysis has shown 10 genes connected to all chemicals present in the mixture and TDs (CAT, GSR, IFNG, IL1B, IL4, IL6, MAPK1, SOD2, TGFB1, TNF), most of which were in co-expression (45.

Carcinogenic and human health risk assessment of children's and adults' exposure to toxic metal(oid)s from air PM in critical sites of the Republic of Serbia.

With global urbanization and industrialization, air pollution has become an inevitable problem. Among air pollutants, toxic metals bound to particulate matter (PM) have a high hazardous potential, contributing to the development of several diseases, including various types of cancer. Due to PM pollution, Serbia is considered to be among the most polluted countries in Europe.

Conducting bioinformatics analysis to predict sulforaphane-triggered adverse outcome pathways in healthy human cells.

Sulforaphane (SFN) is a naturally occurring molecule present in plants from Brassica family. It becomes bioactive after hydrolytic reaction mediated by myrosinase or human gastrointestinal microbiota. Sulforaphane gained scientific popularity due to its antioxidant and anti-cancer properties.

Derivation of benchmark doses for male reproductive toxicity in a subacute low-level Pb exposure model in rats.

The objectives of the study were to simulate low-level Pb exposure scenario in an animal model and to examine reproductive adverse effects. Based on obtained data, we have performed Benchmark dose (BMD)-response modelling. Male Wistar rats were randomized in seven groups (n = 6): one control and six treated with: 0.

Epigenetic mechanisms in metal carcinogenesis.

Many metals exhibit genotoxic and/or carcinogenic effects. These toxic metals can be found ubiquitously - in drinking water, food, air, general use products, in everyday and occupational settings. Exposure to such carcinogenic metals can result in serious health disorders, including cancer.

Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A.

Connections between the mixture containing bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) and liver injury were explored through in silico investigation and 2 in vivo models. Comparative Toxicogenomics Database (CTD), ShinyGO, ToppCluster and Cytoscape were used for bioinformatic analysis. In vivo subacute study was performed on rats - five groups (n = 6): (1) Control: corn oil, (2) DEHP: 50 mg/kg b.

New insight into the perplexing toxic features of PCBs: A study of nephrotoxicity in an animal model.

The present study investigated the effects of PCBs on the rat kidneys with attention given to the determination critical effect dose (CED) using the Benchmark dose (BMD) approach. Male albino Wistar rats (7 animals per group) were given by oral gavage Aroclor 1254 dissolved in corn oil at doses of 0.0, 0.