Glyphosate is the primary active constituent of commercial pesticide Roundup. The present results show that acute Roundup exposure at low doses (36 ppm, 0.036 g/L) for 30 min induces oxidative stress and activates multiple stress-response pathways leading to Sertoli cell death in prepubertal rat testis. increased intracellular Ca2+ concentration by opening L-type voltage-dependent channels as well endoplasmic reticulum IP3 ryanodine receptors, overload within cells, which set off necrotic...

Despite significant advances in early detection and treatment, breast cancer remains a major cause of morbidity mortality. Perfluorooctanoic acid (PFOA) is suspected endocrine disruptor common environmental pollutant associated with various diseases including cancer. However, the effects PFOA its mechanisms action on hormone-responsive cells remain unclear. Here, we explored potential tumorigenic activity (100 nM-1 mM) human epithelial (MCF-10A). MCF-10A exposed to 50 100 µM demonstrated...

Perfluoroalkyl substances (PFAS) have been associated with cancer, but the potential underlying mechanisms need to be further elucidated and include studies of PFAS mixtures. This mechanistic study revealed that very low concentrations (500 pM) binary PFOS PFOA mixture induced synergistic effects on human epithelial breast cell (MCF-10A) proliferation. The proliferation was mediated by pregnane X receptor (PXR) activation, an increase in cyclin D1 CDK6/4 levels, decrease p21 p53 regulation...

Abstract Introduction Apoptosis of neutrophils (polymorphonuclear [PMNs]) may limit inflammatory injury in sepsis and acute respiratory distress syndrome (ARDS), but the relationship between severity extent PMN apoptosis effect superimposed ARDS is unknown. The objective this study was to correlate neutrophil with sepsis-induced ARDS. Methods A prospective cohort conducted intensive care units three tertiary hospitals Porto Alegre, southern Brazil. Fifty-seven patients (uncomplicated sepsis,...

The impact of euthanasia methods on endocrine and metabolic parameters in rodent tissues biological fluids is highly relevant for the accuracy reliability data collected. However, few studies concerning this issue are found literature. We compared effects three currently used animal experimentation (i.e. decapitation, CO2 inhalation pentobarbital injection) serum levels corticosterone, insulin, glucose, triglycerides, cholesterol a range free fatty acids rats. corticosterone insulin were not...

Gene-environment interactions are involved in the development of breast cancer, tumor type that accounts for majority cancer-related deaths among women. Here, we demonstrate exposure to PFOS (10 µM) and PFOA (100 µM)-two contaminants ubiquitously found human blood-for 72 h induced epithelial cell (MCF-10A line) proliferation alteration regulatory cell-cycle proteins (cyclin D1, CDK6, p21, p53, p27, ERK 1/2 p38) persisted after a multitude divisions. The also promoted migration invasion by...

Perfluorooctanesulfonic acid (PFOS) is a synthetic fluorosurfactant widely used in the industry and prominent environmental toxicant. PFOS persistent, bioaccumulative, toxic to mammalian species. Growing evidence suggests that has potential interfere with estrogen homeostasis, posing risk of endocrine-disrupting effects. Recently, concerns about link between breast cancer have been raised, but mechanisms underlying its actions as carcinogen are unknown. By utilizing cell proliferation...

Increased exposure to manmade chemicals may be linked an increase in immune-related diseases humans and immune system dysfunction wildlife. Phthalates are a group of endocrine-disrupting (EDCs) suspected influence the system. The aim this study was characterize persistent effects on leukocytes blood spleen, as well plasma cytokine growth factor levels, one week after end five weeks oral treatment with dibutyl phthalate (DBP; 10 or 100 mg/kg/d) adult male mice. Flow cytometry analysis...

The involvement of calcium-mediated signaling pathways in the mechanism action 1α,25-dihydroxyvitamin D3 (1,25D) is currently demonstrated. In this study we found that 1,25D induces nongenomic effects mediated by membrane vitamin D receptor (VDRm) modulating intermediate filament (IF) phosphorylation and calcium uptake through L-type voltage-dependent channels (L-VDCC) cerebral cortex 10 day-old rats. Results showed involves intra- extracellular levels, as well modulation chloride potassium...

In the present study we investigated effect of in vivo intrastriatal injection quinolinic acid (QA) on cytoskeletal proteins astrocytes and neurons young rats at early stage (30 min) after infusion. QA (150 nmoles/0.5 microL) significantly increased vitro phosphorylation low molecular weight neurofilament subunit (NFL) glial fibrillary acidic protein (GFAP) astrocytes, respectively. This was mediated by cAMP-dependent kinase A (PKA), C (PKC) Ca(2+)/calmodulin-dependent II (PKCaMII)....

Environmental contaminants including long-chain per- and polyfluoroalkyl substances (PFAS) have been linked to cancer, which is a central cause of mortality in humans many wildlife species. Today shorter-chain PFAS are extensively used as replacement compounds commonly found the environment. Mechanistic studies important for better understanding their toxicological potential possible role cancer etiology. Here, we treated normal human breast epithelial cells (MCF-10A) with 500 pM μM...

Congenital hypothyroidism is associated with delay in cell migration and proliferation brain tissue, impairment of synapse formation, misregulation neurotransmitters, hypomyelination mental retardation. However, the mechanisms underlying neuropsychological deficits observed congenital are not completely understood. In present study we proposed a mechanism by which leads to hippocampal neurotoxicity. induces c-Jun-N-terminal kinase (JNK) pathway activation leading hyperphosphorylation glial...

Studies indicate that phthalates are endocrine disruptors affecting reproductive health. One of the most commonly used phthalates, di-n-butyl phthalate (DBP), has been linked with adverse health outcomes in men, but mechanisms behind these effects still poorly understood. Here, adult male mice were orally exposed to DBP (10 or 100 mg/kg/day) for five weeks, and testis adrenal glands collected one week after last dose, examine more persistent effects. Quantification testosterone,...

Concerns have been raised regarding the potential adverse health effects of ubiquitous herbicide glyphosate. Here, we investigated long-term developmental exposure to a glyphosate-based (GBH) by analyzing serum melatonin levels and cellular changes in striatum adult male rats (90 days old). Pregnant lactating were exposed 3% GBH (0.36% glyphosate) through drinking water from gestational day 5 postnatal 15. The offspring showed reduced (43%) at age compared with control group. perinatal also...

Developmental exposure to the environmental neurotoxin β-N-methylamino-L-alanine (BMAA), a proposed risk factor for neurodegenerative disease, can induce long-term cognitive impairments and neurodegeneration in rats. While rodent studies have demonstrated low transfer of BMAA adult brain, this toxin is capable cross placental barrier accumulate fetal brain. Here, we investigated differential susceptibility primary neuronal cells neural stem from rat hippocampus toxicity. Exposure 250 µM...

Di-n-butyl phthalate (DBP) is a ubiquitous environmental contaminant linked with various adverse health effects, including immune system dysfunction. Gut microbial dysbiosis can contribute to wide range of pathogenesis, particularly disease. Here, we investigated the impact DBP on gut microbiome and examined correlations changes after five weeks oral exposure (10 or 100 mg/kg/day) in adult male mice. The fecal composition was characterized using 16S rRNA sequencing. DBP-treated mice...

The studies of signaling mechanisms involved in the disruption cytoskeleton homeostasis were performed a model quinolinic acid (QUIN) neurotoxicity vitro. This investigation focused on phosphorylation level intermediate filament (IF) subunits astrocytes (glial fibrillary acidic protein - GFAP) and neurons (low, medium high molecular weight neurofilament NFL, NFM NFH, respectively). activity phosphorylating system associated with IFs was investigated striatal slices rat exposed to QUIN or...

Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among mechanisms QUIN‐mediated toxicity, disruption cytoskeleton has been demonstrated striatally injected rats and striatal slices. The present work searched for actions QUIN primary neurons. Neurons exposed to 10 µM presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, NFH). Hyperphosphorylation was abrogated presence protein kinase A C inhibitors H89 (20...

Per and polifluorinated substances (PFAS) are ubiquitous persistent contaminants. Studies have indicated that fetuses infants can be exposed to these chemicals in utero through breastfeeding. Despite this, limited data about their effects on brain development available. Here, we compared the of perfluoroctane sulfonate (PFOS) perfluorooctanoic acid (PFOA) exposure rat primary neurons neural stem cells (NSC). Treatment with 1–250 μM either compounds caused no cell viability or proliferation...