Environmental toxicology and pharmacology最新文献

Glyphosate-based herbicides (GBHs) or its active ingredient, glyphosate (Gly), induce implantation failure in rats. We aimed to elucidate a mechanism of action of these compounds assessing the transcriptional and epigenetic status of the receptivity marker, leukemia inhibitory factor (Lif) gene. F0 rats were orally exposed to GBH or Gly at 3.8 or 3.9 mg Gly/kg/day, respectively, from gestational day (GD) 9 until weaning. F1 females were mated and uterine samples collected at GD5. Methylation-sensitive restriction enzymes (MSRE) sites and transcription factors were in silico predicted in regulatory regions of Lif gene. DNA methylation status and histone modifications (histone 3 and 4 acetylation (H3Ac and H4Ac) and H3 lysine-27-trimethylation (H3K27me3)) were assessed. GBH and Gly decreased Lif mRNA levels and caused DNA hypermethylation. GBH increased H3Ac levels, whereas Gly reduced them; both compounds enhanced H3K27me3 levels. Finally, both GBH and Gly induced similar epigenetic alterations in the regulatory regions of Lif.

Miltefosine is the first and only drug approved for the treatment of leishmaniasis. It is also known as a PI3K/AKT signaling pathway inhibitor utilized in anti-cancer or anti-viral therapies. However, the impact of miltefosine on male fertility has not been fully understood. Therefore, this study was performed to investigate the effects of miltefosine on sperm function during capacitation. Duroc spermatozoa were exposed to 0, 2.5, 5, 10, 20, 40, and 80 μM miltefosine and induced for capacitation. Our results showed that miltefosine dramatically increased the expression of PI3K/AKT signaling pathway-associated proteins. Sperm motility, motion kinetics, capacitation, and tyrosine phosphorylation were significantly suppressed by miltefosine. However, intracellular ATP levels and cell viability were not significantly affected. Our findings suggest that miltefosine may disrupt sperm function by abnormally increasing the levels of PI3K/AKT signaling pathway-associated proteins. Therefore, the harmful effects of miltefosine on male reproduction should be considered when using this drug.

Environmental stressors induce specific physiological responses that can be measured in the blood, notably by morphological changes in lymphocytes. Tobacco being the best-known stress in terms of its impact on health, we studied the physiological properties of peripheral blood lymphocytes in a population of 33 healthy non-smokers and smokers. Proteasome amount, mitochondria energy levels, changes in membrane properties and cell and nuclear size were analyzed to obtain 28 parameters from two fluorescence-based techniques: flow cytometry and cell imaging. The results showed that none of the parameters alone identified gender and smoking status, but that statistical analysis of these parameters, whether or not combined with a third set of data, hematological data, can. Statistical analysis of selected parameters clearly discriminates between male and female samples, as well as smokers and non-smokers. Effects of tobacco smoke pollutants are more pronounced in female smokers than in other groups.

Micro- and nanoplastics (MPs/NPs) constitute emerging and widely-distributed environmental contaminants to which humans are highly exposed. They possibly represent a threat for human health. In order to identify cellular/molecular targets for these plastic particles, we have analysed the effects of exposure to manufactured polystyrene (PS) MPs and NPs on in vitro activity and expression of human membrane drug transporters, known to interact with chemical pollutants. PS MPs and NPs, used at various concentrations (1, 10 or 100 µg/mL), failed to inhibit efflux activities of the ATP-binding cassette (ABC) transporters P-glycoprotein, MRPs and BCRP in ABC transporter-expressing cells. Furthermore, PS particles did not impair the transport of P-glycoprotein or BCRP substrates across intestinal Caco-2 cell monolayers. Uptake activities of solute carriers (SLCs) such as OCT1 and OCT2 (handling organic cations) or OATP1B1, OATP1B3, OATP2B1, OAT1 and OAT3 (handling organic anions) were additionally not altered by PS MPs/NPs in HEK-293 cells overexpressing these SLCs. mRNA expression of ABC transporters and of the SLCs OCT1 and OATP2B1 in Caco-2 cells and human hepatic HepaRG cells were finally not impaired by a 48-h exposure to MPs/NPs. Altogether, these data indicate that human drug transporters are unlikely to be direct and univocal targets for synthetic PS MPs/NPs.

Arsenic, a ubiquitous environmental toxicant, has been acknowledged as a significant issue for public health due to its widespread pollution of drinking water and food supplies. The present review aimed to study the toxicity associated with the cardiac system. Prolonged exposure to arsenic has been associated with several harmful health outcomes, especially cardiotoxicity. Arsenic-induced cardiotoxicity encompasses a range of cardiovascular abnormalities, including cardiac arrhythmias, ischemic heart disease, and cardiomyopathy. To tackle this toxicity, understanding the molecular markers, epigenetic predictors, and targets involved in arsenic-induced cardiotoxicity is essential for creating preventative and therapeutic approaches. For preventive measures against this heavy metal poisoning of groundwater, it is crucial to regularly monitor water quality, re-evaluate scientific findings, and educate the public about the possible risks. This review thoroughly summarised what is currently known in this field, highlighting the key molecular markers, epigenetic modifications, and potential therapeutic targets associated with arsenic-induced cardiotoxicity.

Microplastic (MPs) pollution has emerged as a global ecological concern, however, the impact of MPs exposure, particularly in conjunction with other pollutants such as glyphosate (GLY) on honey bee remains unknown. This study investigated the effects of exposure to different concentrations of MPs and their combination with GLY on honey bee larvae development, or during the larvae period, regulation of major detoxification, antioxidant and immune genes, and oxidative stress biomarkers. Results revealed that combined exposure to MPs and GLY decreased larvae survivorship and weight, while exposure to MPs alone showed no significant differences. Both MPs and GLY alone downregulated the defensin-1 gene, but only combined exposure with GLY downregulated the hymenoptaecin gene and increased catalase enzyme activity. The data suggest a synergistic effect of MPs and GLY, leading to immunosuppression and reduced larvae survival and weight. These findings highlight potential risks of two prevalent environmental pollutants on honey bee health.

Medicines, like food, are necessities. Many of the commonly used pharmaceuticals, especially antibiotics and NSAIDs end up in the environment and are detected in it (especially in water) at concentrations in the ng·L⁻¹- μg·L⁻¹ range. Although the concentrations of individual drugs in the environment are low, their high biological activity can cause them to be toxic to the environment. This review analyzes and summarizes the effects of drugs, primarily antibiotics and NSAIDs on photosynthesizing organisms, i.e., algae, aquatic and terrestrial plants. Acute drug toxicity to algae and plants occurs most often at high, often non-existent environmental concentrations, while sublethal effects occur at low drug concentrations. The review also points out the problems associated with ecotoxicological studies and the lack of systemic solutions to better assess the risks associated with the presence of drugs in the environment.

Artificial turf, a consumer product growing in usage in the United States, contains diverse chemicals, some of which are endocrine disruptive. Endocrine effects from turf material extracts have been primarily limited to one component, crumb rubber, of these multi-material products. We present in vitro bioactivities from non-weathered and weathered turf sample extracts, including multiple turf components. All weathered samples were collected from real-world turf fields. Non-weathered versus weathered differentially affected the androgen (AR), estrogen (ER), glucocorticoid (GR), and thyroid receptors (TR) in reporter bioassays. While weathered extracts more efficaciously activated peroxisome proliferator activated receptor γ (PPARγ), this did not translate to greater in vitro adipogenic potential. All turf extracts activated the aryl hydrocarbon receptor (AhR). High AhR-efficacy extracts induced modest rat cardiomyoblast toxicity in an AhR-dependent manner. Our data demonstrate potential endocrine and cardiometabolic effects from artificial turf material extracts, warranting further investigation into potential exposures and human health effects.