Biodegradation of DEP, DIBP, and BBP by a psychrotolerant Sphingobium yanoikuyae strain P4: Degradation potentiality and mechanism study.

Phthalic acid esters (PAEs) are human made chemicals widely used as plasticizers to enhance the flexibility of plastic products. Due to the lack of chemical bonding between phthalates and plastics, these materials can easily enter the environment. Deleterious effects caused by this chemo-pollutant have drawn the attention of the scientific community to remediate them from different ecosystem. In this context, many bacterial strains have been reported across different habitats and Sphingobium yanoikuyae strain P4 is among the few psychrotolerant bacterial species reported to biodegrade simple and complex phthalates. In the present study, biodegradation of three structurally different PAEs viz., diethyl phthalate (DEP), di-isobutyl phthalate (DIBP), and butyl benzyl phthalate (BBP) have been investigated by the strain P4. Quantitative analyses through High-performance liquid chromatography (HPLC) revealed that the bacterium completely degraded 1 g/L of DEP, DIBP, and BBP supplemented individually in minimal media pH 7.0 within 72, 54, and 120 h of incubation, respectively, at 28 °C and under shake culture condition (180 rpm). In addition, the strain could grow in minimal media supplemented individually with up to 3 g/L of DEP and 10.0 g/L of DIBP and BBP at 28 °C and pH 7.0. The strain also could grow in metabolites resulting from biodegradation of DEP, DIBP, and BBP, viz. n-butanol, isobutanol, butyric acid, ethanol, benzyl alcohol, benzoic acid, phthalic acid, and protocatechuic acid. Furthermore, phthalic acid and protocatechuic acid were also detected as degradation pathway metabolites of DEP and DIBP by HPLC, which gave an initial idea about the biodegradation pathway(s) of these phthalates.

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.

In vitro and in vivo exposure of endothelial cells to dibutyl phthalate promotes monocyte adhesion.

The effect of endothelial cells' exposure to dibutyl phthalate (DBP) on monocyte adhesion is largely unknown. We evaluated monocyte adhesion to DBP-exposed endothelial cells by combining three approaches: short-term exposure (24 h) of EA.hy926 cells to 10-6, 10-5, and 10-4 M DBP, long-term exposure (12 weeks) of EA.hy926 cells to 10-9, 10-8, and 10-7 M DBP, and exposure of rats (28 and 90 days) to 100, 500, and 5000 mg DBP/kg food. Monocyte adhesion to human EA.hy926 and rat aortic endothelial cells, expression of selected cellular adhesion molecules and chemokines, and the involvement of extracellular signal-regulated kinase 1/2 (ERK1/2) were analyzed. We observed increased monocyte adhesion to DBP-exposed EA.hy926 cells in vitro and to rat aortic endothelium ex vivo. ERK1/2 inhibitor prevented monocyte adhesion to DBP-exposed EA.hy926 cells in short-term exposure experiments. Increased ERK1/2 phosphorylation in rat aortic endothelium and transient decrease in ERK1/2 activation following long-term exposure of EA.hy926 cells to DBP were also observed. In summary, exposure of endothelial cells to DBP promotes monocyte adhesion, thus suggesting a possible role for this phthalate in the development of atherosclerosis. ERK1/2 signaling could be the mediator of monocyte adhesion to DBP-exposed endothelial cells, but only after short-term high-level exposure.

Identification of sensitive endpoints for the assessment of phthalates-induced reproductive and developmental toxicity: A literature mining study.

Dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), two common types of phthalates, are known to cause reproductive and developmental toxicity in animals and humans. The reference doses (RfD) of DBP and DEHP should be determined by sensitive endpoints. We here aimed to identify sensitive endpoints for DBP- and DEHP-induced such toxicity using published literatures. By examining the impacts of maternal exposure to DBP or DEHP on anogenital distance (AGD) and semen quality of offspring, we discovered that DBP or DEHP caused AGD decline in boys but increase in girls with DBP being more potent and the first 14weeks of pregnancy being more susceptible, suggesting a chemical- and time-dependent phenomenon. We also identified AGD shortening and total sperm count reduction as two sensitive endpoints for DBP- or DEHP-induced reproductive and developmental toxicity, respectively. Based upon these two endpoints and the employment of the Bayesian benchmark dose approach with an uncertainty factor of 3,000, we estimated the RfD values of DBP and DEHP were 15 µg/kg/day and 36 µg/kg/day, respectively. Thus, we uncover previously unrecognized phenomena of DBP- or DEHP-induced reproductive and developmental toxicity and establish new and comparable or more conservative RfDs for the risk assessment of phthalates exposure in humans.

Di-n-butyl phthalate induces toxicity in male fetal mouse testicular development by regulating the MAPK signaling pathway.

"White pollution" has a significant impact on male reproduction. Di-n-butyl phthalate (DBP) is one of the most important factors in this type of pollution. Currently, research from international sources has demonstrated the significant reproductive toxicity of DBP. However, most of these studies have focused mainly on hormones expression at the protein and mRNA levels and the specific molecular targets of DBP and its mechanisms of action remain unclear. In this study, we established a Sprague Dawley pregnant mouse model exposed to DBP, and all male offspring were immediately euthanized at birth and bilateral testes were collected. We found through transcriptome sequencing that cell apoptosis and MAPK signaling pathway are the main potential pathways for DBP induced reproductive toxicity. Molecular biology analyses revealed a significant increase in the protein levels of JNK1(MAPK8) and BAX, as well as a significant increase in the BAX/BCL2 ratio after DBP exposure. Therefore, we propose that DBP induces reproductive toxicity by regulating JNK1 expression to activate the MAPK signaling pathway and induce reproductive cell apoptosis. In conclusion, our study provides the first evidence that the MAPK signaling pathway is involved in DBP-induced reproductive toxicity and highlights the importance of JNK1 as a potential target of DBP in inducing reproductive toxicity.

Evaluation of phthalate migration potential in vacuum-packed.

In recent years, the presence and migration of PAEs in packaging materials and consumer products has become a serious concern. Based on this concern, the aim of our study is to determine the possible migration potential and speed of PAEs in benthic fish stored in vacuum packaging, as well as to monitor the storage time and type as well as polyethylene (PE) polymer detection.As a result of the analysis performed by µ-Raman spectroscopy, 1 microplastic (MP) of 6 µm in size was determined on the 30th day of storage in whiting fish muscle and the polymer type was found to be Polyethylene (PE) (low density polyethylene: LDPE). Depending on the storage time of the packaging used in the vacuum packaging process, it has been determined that its chemical composition is affected by temperature and different types of polymers are formed. 10 types of PAEs were identified in the packaging material and stored flesh fish: DIBP, DBP, DPENP, DHEXP, BBP, DEHP, DCHP, DNOP, DINP and DDP. While the most dominant PAEs in the packaging material were determined as DEHP, the most dominant PAEs in fish meat were recorded as BBP and the lowest as DMP. The findings provide a motivating model for monitoring the presence and migration of PAEs in foods, while filling an important gap in maintaining a safe food chain.

Mitochondrial DNA Stress-Mediated Health Risk to Dibutyl Phthalate Contamination on Zebrafish (Danio rerio) at Early Life Stage.

Plastics contaminations are found globally and fit the exposure profile of the planetary boundary threat. The plasticizer of dibutyl phthalate (DBP) leaching has occurred and poses a great threat to human health and the ecosystem for decades, and its toxic mechanism needs further comprehensive elucidation. In this study, environmentally relevant levels of DBP were used for exposure, and the developmental process, oxidative stress, mitochondrial ultrastructure and function, mitochondrial DNA (mtDNA) instability and release, and mtDNA-cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway with inflammatory responses were measured in zebrafish at early life stage. Results showed that DBP exposure caused developmental impairments of heart rate, hatching rate, body length, and mortality in zebrafish embryo. Additionally, the elevated oxidative stress damaged mitochondrial ultrastructure and function and induced oxidative damage to the mtDNA with mutations and instability of replication, transcription, and DNA methylation. The stressed mtDNA leaked into the cytosol and activated the cGAS-STING signaling pathway and inflammation, which were ameliorated by co-treatment with DBP and mitochondrial reactive oxygen species (ROS) scavenger, inhibitors of cGAS or STING. Furthermore, the larval results suggest that DBP-induced mitochondrial toxicity of energy disorder and inflammation were involved in the developmental defects of impaired swimming capability. These results enhance the interpretation of mtDNA stress-mediated health risk to environmental contaminants and contribute to the scrutiny of mitochondrial toxicants.

Toxic mechanism in Daphnia magna due to phthalic acid esters and CuO nanoparticles co-exposure: The insight of physiological, microbiomic and metabolomic profiles.

Various phthalic acid esters (PAEs) such as dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) co-exist with nanopollutants in aquatic environment. In this study, Daphnia magna was exposed to nano-CuO and DBP or BBP at environmental relevant concentrations for 21-days to investigate these combined toxic effects. Acute EC50 values (48 h) of nano-CuO, DBP, and BBP were 12.572 mg/L, 8.978 mg/L, and 4.785 mg/L, respectively. Results showed that co-exposure with nano-CuO (500 µg/L) for 21 days significantly enhanced the toxicity of DBP (100 µg/L) and BBP (100 µg/L) to Daphnia magna by 18.37% and 18.11%, respectively. The activities of superoxide dismutase, catalase, and glutathione S-transferase were enhanced by 10.95% and 14.07%, 25.63% and 25.91%, and 39.93% and 35.01% in nano-CuO+DBP and nano-CuO+BBP treatments as compared to the individual exposure groups, verifying that antioxidative defense responses were activated. Furthermore, the co-exposure of nano-CuO and PAEs decreased the population richness and diversity microbiota, and changed the microbial community composition in Daphnia magna. Metabolomic analysis elucidated that nano-CuO + PAEs exposure induced stronger disturbance on metabolic network and molecular function, including amino acid, nucleotides, and lipid metabolism-related metabolic pathways, as comparison to PAEs single exposure treatments. In summary, the integration of physiological, microflora, and untargeted metabolomics analysis offers a fresh perspective into the potential ecological risk associated with nanopollutants and phthalate pollution in aquatic ecosystems.

Preparation of novel gallic acid-based dummy-template molecularly imprinted polymer adsorbents for rapid adsorption of dibutyl phthalate from water.

Phthalate esters (PAEs) are plasticizers widely used in the industry and easily released into the environment, posing a serious threat to human health. Molecularly imprinted polymers (MIPs) are important as selective adsorbents for the removal of PAEs. In this study, three kinds of mussel-inspired MIPs for the removal of PAEs were first prepared with gallic acid (GA), hexanediamine (HD), tannic acid (TA), and dopamine (DA) under mild conditions. The adsorption results showed that the MIP with low cost derived from GA and HD (GAHD-MIP) obtained the highest adsorption capacity among these materials. Furthermore, 97.43% of equilibrium capacity could be reached within the first 5 min of adsorption. Especially, the dummy template of diallyl phthalate (DAP) with low toxicity was observed to be more suitable to prepare MIPs than dibutyl phthalate (DBP), although DBP was the target of adsorption. The adsorption process was in accordance with the pseudo-second-order kinetics model. In the isotherm analysis, the adsorption behavior agreed with the Freundlich model. Additionally, the material maintained high adsorption performance after 7 cycles of regeneration tests. The GAHD-MIP adsorbents in this study, with low cost, rapid adsorption equilibrium, green raw materials, and low toxicity dummy template, provide a valuable reference for the design and development of new MIPs.

Assimilation of phthalate esters in bacteria.

The massive usage of phthalate esters (PAEs) has caused serious pollution. Bacterial degradation is a potential strategy to remove PAE contamination. So far, an increasing number of PAE-degrading strains have been isolated, and the catabolism of PAEs has been extensively studied and reviewed. However, the investigation into the bacterial PAE uptake process has received limited attention and remains preliminary. PAEs can interact spontaneously with compounds like peptidoglycan, lipopolysaccharides, and lipids on the bacterial cell envelope to migrate inside. However, this process compromises the structural integrity of the cells and causes disruptions. Thus, membrane protein-facilitated transport seems to be the main assimilation strategy in bacteria. So far, only an ATP-binding-cassette transporter PatDABC was proven to transport PAEs across the cytomembrane in a Gram-positive bacterium Rhodococcus jostii RHA1. Other cytomembrane proteins like major facilitator superfamily (MFS) proteins and outer membrane proteins in cell walls like FadL family channels, TonB-dependent transporters, and OmpW family proteins were only reported to facilitate the transport of PAEs analogs such as monoaromatic and polyaromatic hydrocarbons. The functions of these proteins in the intracellular transport of PAEs in bacteria await characterization and it is a promising avenue for future research on enhancing bacterial degradation of PAEs. KEY POINTS: • Membrane proteins on the bacterial cell envelope may be PAE transporters. • Most potential transporters need experimental validation.

Temporal evolution of plastic additive contents over the last decades in two major European rivers (Rhone and Rhine) from sediment cores analyses.

Although global plastic distribution is at the heart of 21st century environmental concerns, little information is available concerning how organic plastic additives contaminate freshwater sediments, which are often subject to strong anthropogenic pressure. Here, sediment core samples were collected in the Rhone and the Rhine watersheds (France), dated using 137Cs and 210Pbxs methods and analysed for nine phthalates (PAEs) and seven organophosphate esters (OPEs). The distribution of these organic contaminants was used to establish a chronological archive of plastic additive pollution from 1860 (Rhine) and 1930 (Rhone) until today. Sediment grain size and parameters related to organic matter (OM) were also measured as potential factors that may affect the temporal distribution of OPEs and PAEs in sediments. Our results show that OPE and PAE levels increased continuously in Rhone and Rhine sediments since the first records. In both rivers, ∑PAEs levels (from 9.1 ± 1.7 to 487.3 ± 27.0 ng g-1 dry weight (dw) ± standard deviation and from 4.6 ± 1.3 to 65.2 ± 11.2 ng g-1 dw, for the Rhine and the Rhone rivers, respectively) were higher than ∑OPEs levels (from 0.1 ± 0.1 to 79.1 ± 13.7 ng g-1 dw and from 0.6 ± 0.1 to 17.8 ± 2.3 ng g-1 dw, for Rhine and Rhone rivers, respectively). In both rivers, di(2-ethylhexyl) phthalate (DEHP) was the most abundant PAE, followed by diisobutyl phthalate (DiBP), while tris (2-chloroisopropyl) phosphate (TCPP) was the most abundant OPE. No relationship was found between granulometry and additives concentrations, while organic matter helps explain the vertical distribution of PAEs and OPEs in the sediment cores. This study thus establishes a temporal trajectory of PAEs and OPEs contents over the last decades, leading to a better understanding of historical pollution in these two Western European rivers.

Dibutyl phthalate exposure induced mitochondria-dependent ferroptosis by enhancing VDAC2 in zebrafish ZF4 cells.

Dibutyl phthalate (DBP) contamination has raised global concern for decades, while its health risk with toxic mechanisms requires further elaboration. This study used zebrafish ZF4 cells to investigate the toxicity of ferroptosis with underlying mechanisms in response to DBP exposure. Results showed that DBP induced ferroptosis, characterized by accumulation of ferrous iron, lipid peroxidation, and decrease of glutathione peroxidase 4 levels in a time-dependent manner, subsequently reduced cell viability. Transcriptome analysis revealed that voltage-dependent anion-selective channel (VDAC) in mitochondrial outer membrane was upregulated in ferroptosis signaling pathways. Protecting mitochondria with a VDAC2 inhibitor or siRNAs attenuated the accumulation of mitochondrial superoxide and lipid peroxides, the opening of mitochondrial permeability transition pore (mPTP), and the overload of iron levels, suggesting VDAC2 oligomerization mediated the influx of iron into mitochondria that is predominant and responsible for mitochondria-dependent ferroptosis under DBP exposure. Furthermore, the pivotal role of activating transcription factor 4 (ATF4) was identified in the transcriptional regulation of vdac2 by ChIP assay. And the intervention of atf4b inhibited DBP-induced VDAC2 upregulation and oligomerization. Taken together, this study reveals that ATF4-VDAC2 signaling pathway is involved in the DBP-induced ferroptosis in zebrafish ZF4 cells, contributing to the in-depth understanding of biotoxicity and the ecological risk assessment of phthalates.

Molecular insights into the catabolism of dibutyl phthalate in Pseudomonas aeruginosa PS1 based on biochemical and multi-omics approaches.

A comprehensive understanding of the molecular mechanisms underlying microbial catabolism of dibutyl phthalate (DBP) is still lacking. Here, we newly isolated a bacterial strain identified as Pseudomonas aeruginosa PS1 with high efficiency of DBP degradation. The degradation ratios of DBP at 100-1000 mg/L by this strain reached 80-99 % within 72 h without a lag phase. A rare DBP-degradation pathway containing two monobutyl phthalate-catabolism steps was proposed based on intermediates identified by HPLC-TOF-MS/MS. In combination with genomic and transcriptomic analyses, we identified 66 key genes involved in DBP biodegradation and revealed the genetic basis for a new complete catabolic pathway from DBP to Succinyl-CoA or Acetyl-CoA in the genus Pseudomonas for the first time. Notably, we found that a series of homologous genes in Pht and Pca clusters were simultaneously activated under DBP exposure and some key intermediate degradation related gene clusters including Pht, Pca, Xyl, Ben, and Cat exhibited a favorable coexisting pattern, which contributed the high-efficient DBP degradation ability and strong adaptability to this strain. Overall, these results broaden the knowledge of the catabolic diversity of DBP in microorganisms and enhance our understanding of the molecular mechanism underlying DBP biodegradation.

Analysis and remediation of phthalates in aquatic matrices: current perspectives.

Phthalic acid esters (PAEs) are high production volume chemicals used extensively as plasticizers, to increase the flexibility of the main polymer. They are reported to leach into their surroundings from plastic products and are now a ubiquitous environmental contaminant. Phthalate levels have been determined in several environmental matrices, especially in water. These levels serve as an indicator of plasticizer abuse and plastic pollution, and also serve as a route of exposure to different species including humans. Reports published on effects of different PAEs on experimental models demonstrate their carcinogenic, teratogenic, reproductive, and endocrine disruptive effects. Therefore, regular monitoring and remediation of environmental water samples is essential to ascertain their hazard quotient and daily exposure levels. This review summarises the extraction and detection techniques available for phthalate analysis in water samples such as chromatography, biosensors, immunoassays, and spectroscopy. Current remediation strategies for phthalate removal such as adsorption, advanced oxidation, and microbial degradation have also been highlighted.

Di-n-butyl phthalate promotes the neural differentiation of mouse embryonic stem cells through neurogenic differentiation 1.

An understanding of the risk of gene deletion and mutation posed by endocrine-disrupting chemicals (EDCs) is necessary for the identification of etiological reagents for many human diseases. Therefore, the characterization of the genetic traits caused by developmental exposure to EDCs is an important research subject. A new regenerative approach using embryonic stem cells (ESCs) holds promise for the development of stem-cell-based therapies and the identification of novel therapeutic agents against human diseases. Here, we focused on the characterization of the genetic traits and alterations in pluripotency/stemness triggered by phthalate ester derivatives. Regarding their in vitro effects, we reported the abilities of ESCs regarding proliferation, cell-cycle control, and neural ectoderm differentiation. The expression of their stemness-related genes and their genetic changes toward neural differentiation were examined, which led to the observation that the tumor suppressor gene product p53/retinoblastoma protein 1 and its related cascades play critical functions in cell-cycle progression, cell death, and neural differentiation. In addition, the expression of neurogenic differentiation 1 was affected by exposure to di-n-butyl phthalate in the context of cell differentiation into neural lineages. The nervous system is one of the most sensitive tissues to exposure to phthalate ester derivatives. The present screening system provides a good tool for studying the mechanisms underlying the effects of EDCs on the developmental regulation of humans and rodents, especially on the neuronal development of ESCs.

Biodegradation of phthalate acid esters and whole-genome analysis of a novel Streptomyces sp. FZ201 isolated from natural habitats.

Di-n-butyl phthalate (DBP) is one of the most extensively used phthalic acid esters (PAEs) and is considered to be an emerging, globally concerning pollutant. The genus Streptomyces holds promise as a degrader of various organic pollutants, but PAE biodegradation mechanisms by Streptomyces species remain unsolved. In this study, a novel PAE-degrading Streptomyces sp. FZ201 isolated from natural habitats efficiently degraded various PAEs. FZ201 had strong resilience against DBP and exhibited immediate degradation, with kinetics adhering to a first-order model. The comprehensive biodegradation of DBP involves de-esterification, ß-oxidation, trans-esterification, and aromatic ring cleavage. FZ201 contains numerous catabolic genes that potentially facilitate PAE biodegradation. The DBP metabolic pathway was reconstructed by genome annotation and intermediate identification. Streptomyces species have an open pangenome with substantial genome expansion events during the evolutionary process, enabling extensive genetic diversity and highly plastic genomes within the Streptomyces genus. FZ201 had a diverse array of highly expressed genes associated with the degradation of PAEs, potentially contributing significantly to its adaptive advantage and efficiency of PAE degradation. Thus, FZ201 is a promising candidate for remediating highly PAE-contaminated environments. These findings enhance our preliminary understanding of the molecular mechanisms employed by Streptomyces for the removal of PAEs.

Dibutyl phthalate (DBP) promotes Epithelial-Mesenchymal Transition (EMT) to aggravate liver fibrosis into cirrhosis and portal hypertension (PHT) via ROS/TGF-ß1/Snail-1 signalling pathway in adult rats.

OBJECTIVE: The primary objective of this study was to investigate the toxicological impact of Dibutyl phthalate (DBP) on the process of liver fibrosis transitioning into cirrhosis and the subsequent development of portal hypertension (PHT) through the mechanism of epithelial-mesenchymal transition (EMT) mediated by the ROS/TGF-ß/Snail-1 signaling pathway. METHOD: Carbon tetrachloride (CCl4) (1 mg/kg) was introduced in adult rats by oral feeding in CCl4 and CCl4+DBP groups twice a week for 8 weeks, and twice for another 8 week in CCl4 group. DBP was introduced by oral feeding in the CCl4+DBP group twice over the following 8 weeks. We subsequently analyzed hemodynamics measurements and liver cirrhosis degree, hepatic inflammation and liver function in the different groups. EMT related genes expression in rats in the groups of Control, DBP, CCl4 and CCl4+DBP were measured by immunohistochemistry (IHC). Enzyme-linked immunosorbent Assay (ELISA), qRT-PCR, western blot were used to detect the EMT related proteins and mRNA gene expression levels in rats and primary hepatocytes (PHCs). Reactive oxygen species (ROS) were examined with a ROS detection kit. RESULTS: The results showed that the CCl4+DBP group had higher portal pressure (PP) and lower mean arterial pressure (MAP) than the other groups. Elevated collagen deposition, profibrotic factor, inflammation, EMT levels were detected in DBP and CCl4+DBP groups. ROS, TGF-ß1 and Snail-1 were highly expressed after DBP exposure in vitro. TGF-ß1 had the potential to regulate Snail-1, and both of them were subject to regulation by ROS. CONCLUSION: DBP could influence the progression of EMT through its toxicological effect by ROS/TGF-ß1/Snail-1 signalling pathway, causing cirrhosis and PHT in final. The findings of this research might contribute to a novel comprehension of the underlying toxicological mechanisms and animal model involved in the progression of cirrhosis and PHT, and potentially offered a promising therapeutic target for the treatment of the disease.

Combined effect of polystyrene nanoplastic and di-n-butyl phthalate on testicular health of male Swiss albino mice: analysis of sperm-related parameters and potential toxic effects.

Plastics, especially polystyrene nanoplastic particles (PSNPs), are known for their durability and absorption properties, allowing them to interact with environmental pollutants such as di-n-butyl phthalate (DBP). Previous research has highlighted the potential of these particles as carriers for various pollutants, emphasizing the need to understand their environmental impact comprehensively. This study focuses on the subchronic exposure of male Swiss albino mice to PSNP and DBP, aiming to investigate their reproductive toxicity between these pollutants in mammalian models. The primary objective of this study is to examine the reproductive toxicity resulting from simultaneous exposure to PSNP and DBP in male Swiss albino mice. The study aims to analyze sperm parameters, measure antioxidant enzyme activity, and conduct histopathological and morphometric examinations of the testis. By investigating the individual and combined effects of PSNP and DBP, the study seeks to gain insights into their impact on the reproductive profile of male mice, emphasizing potential synergistic interactions between these environmental pollutants. Male Swiss albino mice were subjected to subchronic exposure (60 days) of PSNP (0.2 mg/m, 50 nm size) and DBP (900 mg/kg bw), both individually and in combination. Various parameters, including sperm parameters, antioxidant enzyme activity, histopathological changes, and morphometric characteristics of the testis, were evaluated. The Johnsen scoring system and histomorphometric parameters were employed for a comprehensive assessment of spermatogenesis and testicular structure. The study revealed non-lethal effects within the tested doses of PSNP and DBP alone and in combination, showing reductions in body weight gain and testis weight compared to the control. Individual exposures and the combination group exhibited adverse effects on sperm parameters, with the combination exposure demonstrating more severe outcomes. Structural abnormalities, including vascular congestion, Leydig cell hyperplasia, and the extensive congestion in tunica albuginea along with both ST and Leydig cell damage, were observed in the testis, underscoring the reproductive toxicity potential of PSNP and DBP. The Johnsen scoring system and histomorphometric parameters confirmed these findings, providing interconnected results aligning with observed structural abnormalities. The study concludes that simultaneous exposure to PSNP and DBP induces reproductive toxicity in male Swiss albino mice. The combination of these environmental pollutants leads to more severe disruptions in sperm parameters, testicular structure, and antioxidant defense mechanisms compared to individual exposures. The findings emphasize the importance of understanding the interactive mechanisms between different environmental pollutants and their collective impact on male reproductive health. The use of the Johnsen scoring system and histomorphometric parameters provides a comprehensive evaluation of spermatogenesis and testicular structure, contributing valuable insights to the field of environmental toxicology.

The combined neurotoxicity of DBP and nano-TiO2 in embryonic zebrafish (Danio rerio) revealed by oxidative activity, neuro-development genes expression and metabolomics changes.

Dibutyl phthalate (DBP) is a commonly used plasticizer that is frequently detected in water samples due to its widespread use. Titanium dioxide nanoparticles (n-TiO2) have been found to enhance the harmful effects of organic contaminants by increasing their bioavailability in aquatic environments. However, the combined toxic effects of DBP and n-TiO2 on aquatic organisms remain unclear. This study aimed to investigate the neurotoxicity of DBP and n-TiO2 synergistic exposure during the early life stage of zebrafish. The results of the study revealed that co-exposure of DBP and n-TiO2 led to an increase in deformities and a significant reduction in the active duration of zebrafish larvae. Furthermore, the co-exposure of DBP and n-TiO2 resulted in elevated levels of oxidative stress and altered gene expression related to neurodevelopment and apoptosis. Notably, n-TiO2 exacerbated the oxidative damage and apoptosis induced by DBP alone exposure. Additionally, co-exposure of the 1.0 mg/L DBP and n-TiO2 significantly affected the expression of genes associated with neurodevelopment. Moreover, disturbances in amino acid metabolism and interference with lipid metabolism were observed as a result of DBP and n-TiO2 co-exposure. In general, n-TiO2 aggravated the neurotoxicity of DBP in the early life stage of zebrafish by increasing oxidative stress, apoptosis, and disrupting amino acid synthesis and lipid metabolism. Therefore, it is essential to consider the potential risks caused by DBP and nanomaterials co-existence in the aquatic environment.

Ultrasensitive, Label-Free Voltammetric Detection of Dibutyl Phthalate Based on Poly-l-lysine/poly(3,4-ethylenedioxythiophene)-porous Graphene Nanocomposite and Molecularly Imprinted Polymers.

Development of an efficient technique for accurate and sensitive dibutyl phthalate (DBP) determination is crucial for food safety and environment protection. An ultrasensitive molecularly imprinted polymers (MIP) voltammetric sensor was herein engineered for the specific determination of DBP using poly-l-lysine/poly(3,4-ethylenedioxythiophene)/porous graphene nanocomposite (PLL/PEDOT-PG) and poly(o-phenylenediamine)-imprinted film as a label-free and sensing platform. Fabrication of PEDOT-PG nanocomposites was achieved through a simple liquid-liquid interfacial polymerization. Subsequently, poly-l-lysine (PLL) functionalization was employed to enhance the dispersibility and stability of the prepared PEDOT-PG, as well as promote its adhesion on the sensor surface. In the presence of DBP, the imprinted poly(o-phenylenediamine) film was formed on the surface of PLL/PEDOT-PG. Investigation of the physical properties and electrochemical behavior of the MIP/PLL/PEDOT-PG indicates that the incorporation of PG into PEDOT, with PLL uniformly wrapping its surface, significantly enhanced conductivity, carrier mobility, stability, and provided a larger surface area for specific recognition sites. Under optimal experimental conditions, the electrochemical response exhibited a linear relationship with a logarithm of DBP concentration within the range of 1 fM to 5 µM, with the detection limit as low as 0.88 fM. The method demonstrated exceptional stability and repeatability and has been successfully applied to quantify DBP in plastic packaging materials.