A systematic review of global distribution, sources and exposure risk of phthalate esters (PAEs) in indoor dust.

Phthalate esters (PAEs) are a class of plasticizers that are readily released from plastic products, posing a potential exposure risk to human body. At present, much attention is paid on PAE concentrations in indoor dust with the understanding of PAEs toxicity. This study collected 8187 data on 10 PAEs concentrations in indoor dusts from 26 countries and comprehensively reviewed the worldwide distribution, influencing factors, and health risks of PAEs. Di-(2-ethylhexyl) phthalate (DEHP) is the predominant PAE with a median concentration of 316 µg·g-1 in indoor dust. Polyvinyl chloride wallpaper and flooring and personal care products are the main sources of PAEs indoor dust. The dust concentrations of DEHP show a downward trend over the past two decades, while high dust concentrations of DiNP are found from 2011 to 2016. The median dust contents of 8 PAEs in public places are higher than those in households. Moreover, the concentrations of 9 PAEs in indoor dusts from high-income countries are higher than those from upper-middle-income countries. DEHP in 69.8% and 77.8% of the dust samples may pose a potential carcinogenic risk for adults and children, respectively. Besides, DEHP in 16.9% of the dust samples may pose a non-carcinogenic risk to children. Nevertheless, a negligible risk was found for other PAEs in indoor dust worldwide. This review contributes to an in-depth understanding of the global distribution, sources and health risks of PAEs in indoor dust.

Effect of MEHP on testosterone synthesis via Sirt1/Foxo1/Rab7 signaling pathway inhibition of lipophagy in TM3 cells.

Mono-2-ethylhexyl phthalic acid (MEHP) is the most toxic metabolite of the plasticizer di-2-ethylhexyl phthalic acid (DEHP), and studies have shown that MEHP causes serious reproductive effects. However, its exact mechanisms of action remain elusive. In this study, we aimed to investigate the reproductive effects of MEHP and preliminarily explore its underlying molecular mechanisms. We found that TM3 cells gradually secreted less testosterone and intracellular free cholesterol with increasing MEHP exposure. MEHP exposure inhibited lipophagy and the Sirt1/Foxo1/Rab7 signaling pathway in TM3 cells, causing aberrant accumulation of intracellular lipid droplets. Addition of the Sirt1 agonist SRT1720 and Rab7 agonist ML-098 alleviated the inhibition of lipophagy and increased free cholesterol and testosterone contents in TM3 cells. SRT1720 alleviated the inhibitory effect of MEHP on the Sirt1/Foxo1/Rab7 signaling pathway, whereas ML-098 only alleviated the inhibition of Rab7 protein expression by MEHP and had no effect on Sirt1 and Foxo1 protein expression. This suggests that MEHP inhibits lipophagy in TM3 cells by suppressing the Sirt1/Foxo1/Rab7 signaling pathway, ultimately leading to a further decrease in cellular testosterone secretion. This study improves our current understanding of the toxicity and molecular mechanisms of action of MEHP and provides new insights into the reproductive effects of phthalic acid esters.

Recent advances in toxicological research of di-(2-ethylhexyl)-phthalate: Focus on endoplasmic reticulum stress pathway.

The plasticizer di-(2-ethylhexyl)-phthalate (DEHP) is the most significant phthalate in production, usage, and environmental occurrence. DEHP is found in products such as personal care products, furniture materials, cosmetics, and medical devices. DEHP is noncovalently bind with plastic therefore, repeated uses lead to leaching out of it. Exposure to DEHP plasticizers leads to toxicity in essential organs of the body through various mechanisms. The main objective of this review article is to focus on the DEHP-induced endoplasmic reticulum (ER) stress pathway implicated in the testis, brain, lungs, kidney, heart, liver, and other organs. Not only ER stress, PPAR-related pathways, oxidative stress and inflammation, Ca2+ homeostasis disturbances in mitochondria are also identified as the relative mechanisms. ER is involved in various critical functions of the cell such as Protein synthesis, protein folding, calcium homeostasis, and lipid peroxidation but, DEHP exposure leads to augmentation of misfolded/unfolded protein. This review complies with various recently reported DEHP-induced toxicity studies and some pharmacological interventions that have been shown to be effective through ER stress pathway. DEHP exposure does assess health risks and vulnerability to populations across the globe. This study offers possible targets and approaches for addressing various DEHP-induced toxicity.

Neurotoxicity of dibutyl phthalate in zebrafish larvae: Decreased energy acquisition by neurons.

This work was designed to investigate the neurotoxic effects of the typical plasticizer dibutyl phthalate (DBP) using zebrafish larvae as a model. The results of exhibited that zebrafish larvae exposed to DBP at concentrations of 5 µg/L and 10 µg/L exhibited brain malformations (24 h) and behavioral abnormalities (72 h). After 72 h of exposure to DBP, microglia in the brain were over-activated, reactive oxygen species (ROS) formation was increased, and apoptosis was observed. Meanwhile, it was found that neurons exhibited impaired mitochondrial structure, absent mitochondrial membrane potential and up-regulated autophagy. Further comprehensive biochemical analyses and RNA-Seq, validated by RT-qPCR, glutamate metabolism and PPAR signaling pathway were significantly enriched in the DBP stress group, this may be the main reason for the disruption of glycolysis/gluconeogenesis processes and the reduction of energy substrates for the astrocyte-neuron lactate shuttle (ANLS). In addition, the DBP-exposed group showed aberrant activation of endoplasmic reticulum (ER) stress signaling pathway, which may be related to ROS as well as neuronal apoptosis and autophagy. In conclusion, DBP-induced neurotoxicity may be the combined result of insufficient neuronal energy acquisition, damage to mitochondrial structure, apoptosis and autophagy. These results provide a theoretical basis for understanding the neurotoxic effects of DBP.

Bisphenols can promote antibiotic resistance by inducing metabolic adaptations and natural transformation.

Whether bisphenols, as plasticizers, can influence bacterial uptake of antibiotic resistance genes (ARGs) in natural environment, as well as the underlying mechanism remains largely unknown. Our results showed that four commonly used bisphenols (bisphenol A, S, F, and AF) at their environmental relative concentrations can significantly promote transmission of ARGs by 2.97-3.56 times in Acinetobacter baylyi ADP1. Intriguingly, we observed ADP1 acquired resistance by integrating plasmids uptake and cellular metabolic adaptations other than through reactive oxygen species mediated pathway. Metabolic adaptations including upregulation of capsules polysaccharide biosynthesis and intracellularly metabolic enzymes, which enabled formation of thicker capsules for capturing free plasmids, and degradation of accumulated compounds. Simultaneously, genes encoding DNA uptake and translocation machinery were incorporated to enhance natural transformation of antibiotic resistance carrying plasmids. We further exposed aquatic fish to bisphenols for 120 days to monitor their long-term effects in aquatic environment, which showed that intestinal bacteria communities were dominated by a drug resistant microbiome. Our study provides new insight into the mechanism of enhanced natural transformation of ARGs by bisphenols, and highlights the investigations for unexpectedly-elevated antibiotic-resistant risks by structurally related environmental chemicals.

Di (2-ethylhexyl) phthalate and polystyrene microplastics co-exposure caused oxidative stress to activate NF-κB/NLRP3 pathway aggravated pyroptosis and inflammation in mouse kidney.

Polystyrene microplastic (PS-MPs) contamination has become a worldwide hotspot of concern, and its entry into organisms can cause oxidative stress resulting in multi-organ damage. The plasticizer di (2-ethylhexyl) phthalate (DEHP) is a common endocrine disruptor, these two environmental toxins often occur together, but their combined toxicity to the kidney and its mechanism of toxicity are unknown. Therefore, in this study, we established PS-MPS and/or DEHP-exposed mouse models. The results showed that alone exposure to both PS-MPs and DEHP caused inflammatory cell infiltration, cell membrane rupture, and content spillage in kidney tissues. There were also down-regulation of antioxidant enzyme levels, increased ROS content, activated of the NF-κB pathway, stimulated the levels of heat shock proteins (HSPs), pyroptosis, and inflammatory associated factors. Notably, the co-exposure group showed greater toxicity to kidney tissues, the cellular assay further validated these results. The introduction of the antioxidant n-acetylcysteine (NAC) and the NLRP3 inhibitor (MCC950) could mitigate the changes in the above measures. In summary, co-exposure of PS-MPs and DEHP induced oxidative stress that activated the NF-κB/NLRP3 pathway and aggravated kidney pyroptosis and inflammation, as well as that HSPs are also involved in this pathologic injury process. This study not only enriched the nephrotoxicity of plasticizers and microplastics, but also provided new insights into the toxicity mechanisms of multicomponent co-pollution in environmental.

Exposure to the plasticizer diisopentyl phthalate can cause Vero cell line death.

Phthalates are synthetic plasticizers present in the daily lives of humans, as part of the composition of different products, such as food packaging, water bottles, and toys. These compounds can migrate from plastic materials to the environment changing biological systems. Although diisopentyl phthalate (DiPeP) is largely used in Brazil, there is a lack of information on the possible toxic effects of this compound. This research aims to evaluate the toxicity of DiPeP in the Vero renal cells. These cells were exposed to the 1-1000 µM of DiPeP for 24 and 72 h and subsequently, the cytotoxicity, apoptosis and necrosis-inducing potential, and antioxidant system (SOD, GPx, and GST) were investigated. DiPeP neither caused cytotoxicity nor altered SOD and GPx activity, although GST has been increased at 100 or 1 µM (24 and 72 h, respectively). However, cell death by apoptosis and necrosis was observed. These results indicate that DiPeP caused cell death by a non-oxidative stress-mediated mechanism, which shows the relevance of investigate other process in further researches.

Exposure to the plasticizer dibutyl phthalate causes oxidative stress and neurotoxicity in brain tissue.

The phthalate ester, dibutyl phthalate (DBP), is one of the endocrine-disrupting chemicals detected in various aquatic environments. Previous research has found multiple toxic effects of DBP in aquatic organisms; however, the neurotoxic effects of the compound are surprisingly scanty. The purpose of this study was aimed to evaluate the role of oxidative stress in the induction of neurotoxicity in the brain tissue of the fish Pseudetroplus maculatus. The fish were exposed to the sublethal concentration of DBP (200 µg L-1) for 1, 4, 7, and 15 days along with control and vehicle control groups. The induction of oxidative stress in the brain subcellular fractions was proved by alterations in the activities of superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase along with the reduction in the total antioxidant capacity. Meanwhile, the levels of hydrogen peroxide and lipid peroxidation were increased. Neurotransmitters such as acetylcholine, dopamine, adrenaline, noradrenaline, and serotonin were altered in all subcellular fractions suggesting the disruption of the neurotransmitter system in the fish brain. These results indicate that DBP induces oxidative stress, which correlates with neurotoxicity in Pseudetroplus maculatus brain tissue.

Ca2+ homeostasis imbalance induced by Pparg: A key factor in di (2-ethylhexyl) phthalate (DEHP)-induced cardiac dysfunction in zebrafish larvae.

Widespread application of the typical phthalate plasticizers, di (2-ethylhexyl) phthalate (DEHP), poses a serious potential threat to the health of animals and even humans. Previous studies have confirmed the mechanism of DEHP-induced cardiac developmental defects in zebrafish larvae. However, the mechanism of cardiac dysfunction is still unclear. Thus, this work aimed to comprehensively investigate the mechanisms involved in DEHP-induced cardiac dysfunction through computational simulations, in vivo assays in zebrafish, and in vitro assays in cardiomyocytes. Firstly, molecular docking and western blot initially investigated the activating effect of DEHP on Pparg in zebrafish. Although GW9662 (PPARG antagonist) effectively alleviated DEHP-induced cardiac dysfunction and lipid metabolism disorders, it did not restore significant decreases in mitochondrial membrane potential and ATP levels. In vitro assays in cardiomyocytes, DEHP caused overexpression of PPARG and proteins involved in the regulation of Ca2+ homeostasis, and the above abnormalities were effectively alleviated by GW9662, suggesting that the Ca2+ homeostatic imbalance caused by activation of PPARG by DEHP seems to be the main cause of DEHP-induced cardiac dysfunction. To sum up, this work not only refines the mechanism of toxic effects of cardiotoxicity induced by DEHP, but provides an important theoretical basis for enriching the toxicological effects of DEHP.

Maternal exposure to dibutyl phthalate (DBP) impairs angiogenesis and AR signalling pathway through suppression of TGFB1I1 in hypospadias offspring.

Early exposure to dibutyl phthalate (DBP) can cause hypospadias in newborn foetuses. However, the underlying molecular mechanism is not well defined. Aberrant angiogenesis is associated with various dysplasias including urogenital deficits. In vivo and in vitro angiogenesis assays showed reduced angiogenesis in the hypospadias group and DBP exposed group. RNA-sequencing analysis of DBP-treated HUVECs revealed decreased expression of transforming growth factor beta 1-induced transcript 1 (TGFB1I1) and a significantly enriched angiogenesis-associated pathway. Further experiments revealed that decreased TGFB1I1 expression was associated with disrupted tube formation and migration, which resulted in decreased angiogenesis. Functional assays revealed that the overexpression of TGFB1I1 promoted tube formation and migration of HUVECs in the DBP-treated group. Moreover, we showed that the transcription factor AR was regulated by TGFB1I1 through inhibiting its translocation from the cytoplasm to the nucleus. Together, our results identified TGFB1I1 as a component of aberrant angiogenesis in hypospadias rats and its interaction with AR might be a potential target for hypospadias development.

Inhibitory effects of phthalate esters (PAEs) and phthalate monoesters towards human carboxylesterases (CESs).

Phthalate esters (PAEs), accompanied by phthalate monoesters as hydrolysis metabolites in humans, have been widely used as plasticizers and exhibited disruptive effects on the endocrine and metabolic systems. The present study aims to investigate the inhibition behavior of PAEs and phthalate monoesters on the activity of the important hydrolytic enzymes, carboxylesterases (CESs), to elucidate the toxicity mechanism from a new perspective. The results showed significant inhibition on CES1 and CES2 by most PAEs, but not by phthalate monoesters, above which the activity of CES1 was strongly inhibited by DCHP, DEHP, DiOP, DiPP, DNP, DPP and BBZP, with inhibition ratios exceeding 80%. Kinetic analyses and in vitro-in vivo extrapolation were conducted, revealing that PAEs have the potential to disrupt the metabolism of endogenous substances catalyzed by CES1 in vivo. Molecular docking results revealed that hydrogen bonds and hydrophobic contacts formed by ester bonds contributed to the interaction of PAEs towards CES1. These findings will be beneficial for understanding the adverse effect of PAEs and phthalate monoesters.

Diethyl phthalate, a plasticizer, induces adipocyte inflammation and apoptosis in mice after long-term dietary administration.

The incidence of metabolic diseases is increasing alarmingly in recent times. Parallel to nutritional excess and sedentary lifestyle, the random usage of several endocrine disrupting chemicals including plasticizers is reported to be closely associated with metabolic diseases. Diethyl phthalate (DEP) is a widely used plasticizer in a host of consumer and daily care products. Adipose tissue plays a central role in energy storage and whole-body metabolism. The impairment of adipose function is critically implicated in the pathogenesis of insulin resistance, diabetes, and related metabolic diseases. Recently, exposure to certain phthalate esters has been linked to the development of obesity and diabetes, although there are contradictions and the mechanisms are not clearly understood. In an effort to ascertain the metabolic consequences of chronic phthalate exposure and the underlying mechanism, the present study was designed to examine the effects of long-term dietary consumption of DEP in adipocytes. DEP-treated mice were hyperglycemic but nonobese; their body weight initially increased which subsequently was reduced compared to control. DEP exposure at lower levels impaired adipogenesis by downregulating the key transcription factor, peroxisome proliferator-activated receptor γ and its downstream insulin-sensitizing adipokine, adiponectin, thereby severely compromising adipocyte function. The activation of master regulator nuclear factor κB led to rise in proinflammatory cytokines. We found that DEP triggered intrinsic apoptotic pathways through activated cytochrome c-Apaf1-caspase 9-caspase 3 axis in adipocytes. Taken together, our data revealed that chronic administration of dietary DEP could unleash adverse metabolic outcomes by initiating oxidative stress, inflammation, and apoptosis in the adipocytes, thus leading to adipose tissue dysfunction.

Plasticizer acetyl triethyl citrate (ATEC) induces lipogenesis and obesity.

Environmental chemicals, such as plasticizers, have been linked to increased rates of obesity, according to epidemiological studies. Acetyl triethyl citrate (ATEC) is a plasticizer that is commonly utilized in pharmaceutical products and food packaging as a non-phthalate alternative. Due to its direct contact with the human body and high leakage rate from the polymers, assessment of the potential risk of ATEC exposure at environmentally relevant low doses to human health is needed. Male C57BL/6 J mice were fed diets containing ATEC at doses of either 0.1 or 10 µg/kg per day in a period of 12 weeks to mimic the real exposure environment. The findings suggest that in C57BL/6 J mice, ATEC exposure resulted in increased body weight gain, body fat percentage, and benign hepatocytes, as well as adipocyte size. Consistent with in vivo models, ATEC treatment obviously stimulated the increase of intracellular lipid load in both mouse and human hepatocytes. Mechanically, ATEC induced the transcriptional expression of genes involved in de novo lipogenesis and lipid uptake. Using both enzyme inhibitor and small interfering RNA (siRNA) transfection, we found that stearoyl-coenzyme A desaturase 1 (SCD1) played a significant role in ATEC-induced intracellular lipid accumulation. This study for the first time provided initial evidence suggesting the obesogenic and fatty liver-inducing effect of ATEC at low doses near human exposure levels, and ATEC might be a potential environmental obesogen and its effect on human health need to be further evaluated.

Lycium barbarum polysaccharides attenuate oxidative stress and mitochondrial toxicity induced by mixed plasticizers in HepG2 cells through activation of Nrf2.

AIMS: In daily life, it is common for humans to be exposed to multiple phthalate esters (PAEs). However, there is limited research on the mechanisms and intervention of combined PAEs toxicity. This study aims to explore the cytotoxicity of combined PAEs and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. MAIN METHODS: LBP (62.5, 125 and 250 µg/mL) were applied to intervene HepG2 cells treated with DEHP and DBP mixtures (50, 100, 200, 400 and 800 µg/mL). Western Blot and different kits were mainly performed in our study. KEY FINDINGS: DEHP and DBP mixtures suppressed the expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and activated MAPK pathway by increasing ROS. Combined DEHP and DBP exposure reduced ATP content and inhibited the mitochondrial biogenesis pathway in HepG2 cells through oxidative stress, which in turn caused cytotoxicity. LBP reduced oxidative stress and cell death induced by mixed plasticizers, upregulated Nrf2 levels and mitochondrial biogenesis pathway levels and inhibited MAPK pathway activation. Notably, after treating HepG2 cells with Nrf2-specific inhibitor (ML385, 0.5 µM), we found that the activation of Nrf2 played a crucial role on LBP intervention of DEHP and DBP induced HepG2 cytotoxicity. SIGNIFICANCE: This study not only enhances our understanding of the toxicological effects caused by combined PAEs exposure, but also has significant implications in devising strategies to mitigate the toxicological consequences of combined exposure to exogenous chemicals through the investigation of the role of LBP.

PPARß/δ-ANGPTL4 axis mediates the promotion of mono-2-ethylhexyl phthalic acid on MYCN-amplified neuroblastoma development.

Di-2-ethylhexyl phthalic acid (DEHP) is one of the most widely used plasticizers in the industry, which can improve the flexibility and durability of plastics. It is prone to migrate from various daily plastic products through wear and leaching into the surrounding environment and decompose into the more toxic metabolite mono-2-ethylhexyl phthalic acid (MEHP) after entering the human body. However, the impacts and mechanisms of MEHP on neuroblastoma are unclear. We exposed MYCN-amplified neuroblastoma SK-N-BE(2)C cells to an environmentally related concentration of MEHP and found that MEHP increased the proliferation and migration ability of tumor cells. The peroxisome proliferator-activated receptor (PPAR) ß/δ pathway was identified as a pivotal signaling pathway in neuroblastoma, mediating the effects of MEHP through transcriptional sequencing analysis. Because MEHP can bind to the PPARß/δ protein and initiate the expression of the downstream gene angiopoietin-like 4 (ANGPTL4), the PPARß/δ-specific agonist GW501516 and antagonist GSK3787, the recombinant human ANGPTL4 protein, and the knockdown of gene expression confirmed the regulation of the PPARß/δ-ANGPTL4 axis on the malignant phenotype of neuroblastoma. Based on the critical role of PPARß/δ and ANGPTL4 in the metabolic process, a non-targeted metabolomics analysis revealed that MEHP altered multiple metabolic pathways, particularly lipid metabolites involving fatty acyls, glycerophospholipids, and sterol lipids, which may also be potential factors promoting tumor progression. We have demonstrated for the first time that MEHP can target binding to PPARß/δ and affect the progression of neuroblastoma by activating the PPARß/δ-ANGPTL4 axis. This mechanism confirms the health risks of plasticizers as tumor promoters and provides new data support for targeted prevention and treatment of neuroblastoma.

DEHP and DINP accelerate aging effects in male and female of Drosophila melanogaster depend on AKT/FOXO pathway.

Phthalates are commonly used as plasticizers. Numerous studies have focused on endocrine, reproductive, and developmental toxicity of phthalates exposure to male organisms. In recent years, some studies looking into the aging effects of phthalates exposure in D. melanogaster showed discrepant results. In this study, we compared the different concentrations of Di(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DINP) for acute and chronic treatment for different gender D. melanogaster and explored the potential mechanism of DEHP and DINP exposure. The results showed that acute exposure to DEHP or DINP at a high dose significantly decreased the lifespan of female and male D. melanogaster under HFD stress. Chronic exposure significantly decreased the lifespan of flies in all exposure groups except for the low-dose DINP exposure female group. Among them, in the normal feeding group, we found that female flies seemed to be more resistant to DEHP or DINP exposure. Meanwhile, the locomotion ability and fertility of flies exhibited a dose-dependent decline. Furthermore, phthalates did not significantly reduce the lifespan or health status of akt and foxo mutant flies in the mutant fly assays, and real-time quantitative-PCR (q-PCR) data revealed akt and foxo significant change with 10 µM DEHP or DINP treatment. This suggests that akt and foxo played a role in the process by which DEHP and DINP caused age-related declines in D. melanogaster.

Melatonin alleviates the toxic effect of di(2-ethylhexyl) phthalate on oocyte quality resulting from CEBPB suppression during primordial follicle formation.

Presently, the exposure of plasticizers to humans and animals occurs daily, which pose a potential threat to reproductive health. In the present study, a pregnant mouse model exposed to di(2-ethylhexyl) phthalate (DEHP, one of the most common plasticizers) and melatonin was established, and the single-cell transcriptome technology was applied to investigate the effects of melatonin in ovarian cells against DEHP. Results showed that DEHP markedly altered the gene expression pattern of ovarian cells, and severely weakened the histone methylation modification of oocytes. The administration of melatonin recovered the expression of LHX8 and SOHLH1 proteins that essential for primordial follicle formation, and increased the expression of CEBPB, as well as key genes of histone methylation modification (such as Smyd3 and Kdm5a). In addition, the ovarian damage caused by DEHP was also relieved after the overexpression of CEBPB, which suggested melatonin could improve primordial follicle formation progress via enhancing CEBPB expression in mice. Besides, the apoptosis of ovarian cells induced by DEHP also was diminished by melatonin. The study provides evidence of melatonin preventing the damage mediated by plasticizers on the reproductive system in females and CEBPB may serve as a downstream target factor of melatonin in the process.

Comparative analysis of diisononyl phthalate and di(isononyl)cyclohexane-1,2 dicarboxylate plasticizers in regulation of lipid metabolism in 3T3-L1 cells.

Diisononyl phthalate (DINP) and di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) are plasticizers introduced to replace previously used phthalate plasticizers in polymeric products. Exposure to DINP and DINCH has been shown to impact lipid metabolism. However, there are limited studies that address the mechanisms of toxicity of these two plasticizers. Here, a comparative toxicity analysis has been performed to evaluate the impacts of DINP and DINCH on 3T3-L1 cells. The preadipocyte 3T3-L1 cells were exposed to 1, 10, and 100 µM of DINP or DINCH for 10 days and assessed for lipid accumulation, gene expression, and protein analysis. Lipid staining showed that higher concentrations of DINP and DINCH can induce adipogenesis. The gene expression analysis demonstrated that both DINP and DINCH could alter the expression of lipid-related genes involved in adipogenesis. DINP and DINCH upregulated Pparγ, Pparα, C/EBPα Fabp4, and Fabp5, while both compounds significantly downregulated Fasn and Gata2. Protein analysis showed that both DINP and DINCH repressed the expression of FASN. Additionally, we analyzed an independent transcriptome dataset encompassing temporal data on lipid differentiation within 3T3-L1 cells. Subsequently, we derived a gene set that accurately portrays significant pathways involved in lipid differentiation, which we subsequently subjected to experimental validation through quantitative polymerase chain reaction. In addition, we extended our analysis to encompass a thorough assessment of the expression profiles of this identical gene set across 40 discrete transcriptome datasets that have linked to diverse pathological conditions to foreseen any potential association with DINP and DINCH exposure. Comparative analysis indicated that DINP could be more effective in regulating lipid metabolism.

Di (2-ethylhexyl) phthalate alters neurobehavioral responses and oxidative status, architecture, and GFAP and BDNF signaling in juvenile rat's brain: Protective role of Coenzyme10.

Di-(2-ethylhexyl) phthalate (DEHP), a phthalate plasticizer, is widely spread in the environment, presenting hazards to human health and food safety. Hence, this study examined the probable preventive role of coenzyme10 (CQ10) (10 mg/kg.b.wt) against DEHP (500 mg/kg.wt) - induced neurotoxic and neurobehavioral impacts in juvenile (34 ± 1.01g and 3 weeks old) male Sprague Dawley rats in 35-days oral dosing trial. The results indicated that CQ10 significantly protected against DEHP-induced memory impairment, anxiety, depression, spatial learning disorders, and repetitive/stereotypic-like behavior. Besides, the DEHP-induced depletion in dopamine and gamma amino butyric acid levels was significantly restored by CQ10. Moreover, CQ10 significantly protected against the exhaustion of CAT, GPx, SOD, GSH, and GSH/GSSG ratio, as well as the increase in malondialdehyde, Caspas-3, interleukin-6, and tumor necrosis factor-alpha brain content accompanying with DEHP exposure. Furthermore, CQ10 significantly protected the brain from the DEHP-induced neurodegenerative alterations. Also, the increased immunoexpression of brain-derived neurotrophic factor, not glial fibrillary acidic protein, in the cerebral, hippocampal, and cerebellar brain tissues due to DEHP exposure was alleviated with CQ10. This study's findings provide conclusive evidence that CQ10 has the potential to be used as an efficient natural protective agent against the neurobehavioral and neurotoxic consequences of DEHP.

Organophosphate ester flame retardants and plasticizers in house dust and mental health outcomes among Canadian mothers: A nested prospective cohort study in CHILD.

Organophosphate ester flame retardants and plasticizers (OPEs) are common exposures in modern built environments. Toxicological models report that some OPEs reduce dopamine and serotonin in the brain. Deficiencies in these neurotransmitters are associated with anxiety and depression. We hypothesized that exposure to higher concentrations of OPEs in house dust would be associated with a greater risk of depression and stress in mothers across the prenatal and postpartum periods. We conducted a nested prospective cohort study using data collected on mothers (n = 718) in the CHILD Cohort Study, a longitudinal multi-city Canadian birth cohort (2008-2012). OPEs were measured in house dust sampled at 3-4 months postpartum. Maternal depression and stress were measured at 18 and 36 weeks gestation and 6 months and 1 year postpartum using the Centre for Epidemiologic Studies for Depression Scale (CES-D) and Perceived Stress Scale (PSS). We used linear mixed models to examine the association between a summed Z-Score OPE index and continuous depression and stress scores. In adjusted models, one standard deviation increase in the OPE Z-score index was associated with a 0.07-point (95% CI: 0.01, 0.13) increase in PSS score. OPEs were not associated with log-transformed CES-D (ß: 0.63%, 95% CI: -0.18%, 1.46%). The effect of OPEs on PSS score was strongest at 36 weeks gestation and weakest at 1 year postpartum. We observed small increases in maternal perceived stress levels, but not depression, with increasing OPEs measured in house dust during the prenatal and early postpartum period in this cohort of Canadian women. Given the prevalence of prenatal and postpartum anxiety and the ubiquity of OPE exposures, additional research is warranted to understand if these chemicals affect maternal mental health.