Toxicological Behavior Research Articles

In silico and in vitro chemometrics, cell toxicity and permeability of naringenin 8-sulphonate and derivatives.

Sulphur containing natural compounds are among the most biologically relevant metabolites in vivo. Naringenin 8-sulphonate from Parinari excelsa Sabine was evaluated in a previous work, demonstrating ability to act as a natural anti-inflammatory. Although the interference of this molecule against different inflammatory mediators was described, there is no information regarding its potential toxicity and pharmacokinetics, which are essential for its capacity to reach its therapeutic targets. In fact, despite the existence of reports on naringenin ADMET properties, the influence of sulphation patterns on them remains unknown. This work aims to assess the in vitro pharmacokinetic and toxicological behavior of naringenin 8-sulphonate, as well as to understand the importance of the presence and position of the sulphur containing group for that. Naringenin 8-sulphonate physicochemical and ADMET properties were investigated using in silico tools and cell-based in vitro models. At the same time, naringenin and naringenin 4'-O-sulphate were investigated to evaluate the impact of the sulphonate group on the results. ADMETlab 2.0 in silico tool was used to predict the compounds' physicochemical descriptors. Pharmacokinetic properties were determined experimentally in vitro. While MRC-5 lung fibroblasts and HaCaT keratinocytes were used to evaluate the cytotoxicity of samples through MTT and LDH assays, Caco-2 human intestinal epithelial cells were used for the determination of genotoxicity, through alkaline comet assay, and as a permeability model to assess the ability of compounds to cross biological barriers. Experimental determinations showed that none of the compounds was cytotoxic. In terms of genotoxicity, naringenin 8-sulphonate and naringenin caused significant DNA fragmentation, whereas naringenin 4'-O-sulphate did not. When it comes to permeability, the two sulphur-containing compounds with a sulphur containing group were clearly less capable to cross the Caco-2 cell barrier than naringenin. In this study, we conclude that the sulphur containing group from naringenin 8-sulphonate is disadvantageous for the molecule in terms of ADMET properties, being particularly impactful in the permeability in intestinal barrier models. Thus, this work provides important insights regarding the role of flavonoids sulphation and sulphonation upon pharmacokinetics and toxicity.

Cellular and Mitochondrial Toxicity of Tolcapone, Entacapone, and New Nitrocatechol Derivatives.

Nitrocatechols are the standard pharmacophore to develop potent tight-binding inhibitors of catechol O-methyltransferase (COMT), which can be used as coadjuvant drugs to manage Parkinson's disease. Tolcapone is the most potent drug of this class, but it has raised safety concerns due to its potential to induce liver damage. Tolcapone-induced hepatotoxicity has been attributed to the nitrocatechol moiety; however, other nitrocatechol-based COMT inhibitors, such as entacapone, are safe and do not damage the liver. There is a knowledge gap concerning which mechanisms and chemical properties govern the toxicity of nitrocatechol-based COMT inhibitors. Using a vast array of cell-based assays, we found that tolcapone-induced toxicity is caused by direct interference with mitochondria that does not depend on bioactivation by P450. Our findings also suggest that (a) lipophilicity is a key property in the toxic potential of nitrocatechols; (b) the presence of a carbonyl group directly attached to the nitrocatechol ring seems to increase the reactivity of the molecule, and (c) the presence of cyano moiety in double bond stabilizes the reactivity decreasing the cytotoxicity. Altogether, the fine balance between lipophilicity and the chemical nature of the C1 substituents of the nitrocatechol ring may explain the difference in the toxicological behavior observed between tolcapone and entacapone.

In Vivo Toxicological Analysis of the ZnFe2O4@poly(tBGE-alt-PA) Nanocomposite: A Study on Fruit Fly.

Recently, the use of hybrid nanomaterials (NMs)/nanocomposites has widely increased for the health, energy, and environment sectors due to their improved physicochemical properties and reduced aggregation behavior. However, prior to their use in such sectors, it is mandatory to study their toxicological behavior in detail. In the present study, a ZnFe2O4@poly(tBGE-alt-PA) nanocomposite is tested to study its toxicological effects on a fruit fly model. This nanocomposite was synthesized earlier by our group and physicochemically characterized using different techniques. In this study, various neurological, developmental, genotoxic, and morphological tests were carried out to investigate the toxic effects of nanocomposite on Drosophila melanogaster. As a result, an abnormal crawling speed of third instar larvae and a change in the climbing behavior of treated flies were observed, suggesting a neurological disorder in the fruit flies. DAPI and DCFH-DA dyes analyzed the abnormalities in the larva's gut of fruit flies. Furthermore, the deformities were also seen in the wings and eyes of the treated flies. These obtained results suggested that the ZnFe2O4@poly(tBGE-alt-PA) nanocomposite is toxic to fruit flies. Moreover, this is essential to analyze the toxicity of this hybrid NM again in a rodent model in the future.

In vitro evaluation of the carcinogenic potential of perfluorinated chemicals.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the major components of long-chain per- and polyfluorinated alkyl substances (PFAS), known for their chemical stability and environmental persistence. Even if PFOA and PFOS have been phased out or are limited in use, they still represent a concern for human and environmental health. Several studies have been per­formed to highlight the toxicological behavior of these chemicals and their mode of action (MoA). Data have suggested a causal association between PFOA or PFOS exposure and carcinogenicity in humans, but the outcomes of epidemiological studies showed some inconsistency. Moreover, the hypothesized MoA based on animal studies is considered not relevant for human cancer. To improve the knowledge on PFAS toxicology and contribute to the weight of evidence for the regu­latory classification of PFAS, we used the BALB/c 3T3 cell transformation assay (CTA), an in vitro model under consideration to be included in an integrated approach to testing and assessment for non-genotoxic carcinogens (NGTxCs). PFOS and PFOA were tested at several concentrations using a validated experimental protocol. Our results demonstrate that PFOA does not induce cell transformation, whereas PFOS exposure induced a concentration-related increase of type III foci. Malignant foci formation was triggered at PFOS concentrations equal to or higher than 50 ppm and was not directly associated with cytotoxicity or proliferation induction. The divergent CTA outcomes suggest that different molecular events could be responsible for the toxicological profiles of PFOS and PFOA, which were not fully captured in our study.

New insight into PAH4 induced hepatotoxicity and the dose-response assessment in rats model

PAH4 (sum of benzo[a]pyrene, chrysene, benz[a]anthracene and benzo[b]fluoranthene) has been proposed as better marker than benzo[a]pyrene to assess total PAHs exposure in foodstuffs. However, the toxicological behaviors of PAH4 combined exposure remain unclear. This study aimed to investigate PAH4 toxicity effects with non-targeted metabolomics approach and evaluate the external and internal dose-response relationships based on benchmark dose (BMD) analysis. Male Sprague-Dawley rats were treated by gavage with vehicle (corn oil) or four doses of PAH4 (10, 50, 250, 1000 μg/kg·bw) for consecutive 30 days. After the final dose, the liver, blood and urine samples of rats were subsequently collected for testing. The concentrations of urinary mono-hydroxylated PAHs metabolites (OH-PAHs) including 3-hydroxybenzo[a]pyrene (3-OHB[a]P), 3-hydroxychrysene (3-OHCHR) and 3-hydroxybenz[a]anthracene (3-OHB[a]A) were determined to reflect internal PAH4 exposure. Our results showed PAH4 exposure increased relative liver weight and serum aspartate aminotransferase (AST) activity and caused hepatocyte swelling and degeneration, implying hepatotoxicity induced by PAH4. Serum metabolomics suggested PAH4 exposure perturbed lipid metabolism through upregulating the expression of glycerolipids metabolites, which was evidenced by markedly increased serum triglyceride (TG) level and hepatic TG content. Additionally, urinary OH-PAHs concentrations presented strong positive correlations with the external dose, indicating they were able to reflect PAH4 exposure. Furthermore, PAH4 exposure led to a dose-response increase of hepatic TG content, based on which the 95% lower confidence value of BMDs for external and internal doses were estimated as 5.45 μg/kg·bw and 0.11 μmol/mol·Cr, respectively. In conclusion, this study suggested PAH4 exposure could induce hepatotoxicity and lipid metabolism disorder, evaluating the involved dose-response relationships and providing a basis for the risk assessment of PAHs.

Meta-Analysis of Integrated Proteomic and Transcriptomic Data Discerns Structure-Activity Relationship of Carbon Materials with Different Morphologies.

The Fiber Pathogenicity Paradigm (FPP) establishes connections between fiber structure, durability, and disease-causing potential observed in materials like asbestos and synthetic fibers. While emerging nanofibers are anticipated to exhibit pathogenic traits according to the FPP, their nanoscale diameter limits rigidity, leading to tangling and loss of fiber characteristics. The absence of validated rigidity measurement methods complicates nanofiber toxicity assessment. By comprehensively analyzing 89 transcriptomics and 37 proteomics studies, this study aims to enhance carbon material toxicity understanding and proposes an alternative strategy to assess morphology-driven toxicity. Carbon materials are categorized as non-fibrous, high aspect ratio with shorter lengths, tangled, and rigid fibers. Mitsui-7 serves as a benchmark for pathogenic fibers. The meta-analysis reveals distinct cellular changes for each category, effectively distinguishing rigid fibers from other carbon materials. Subsequently, a robust random forest model is developed to predict morphology, unveiling the pathogenicity of previously deemed non-pathogenic NM-400 due to its secondary structures. This study fills a crucial gap in nanosafety by linking toxicological effects to material morphology, in particular regarding fibers. It demonstrates the significant impact of morphology on toxicological behavior and the necessity of integrating morphological considerations into regulatory frameworks.

Contribution of free hydroxyl radical to the formation of micro(nano)plastics and release of additives during polyethylene degradation in water

The omnipresence of secondary microplastics (MPs) in aquatic ecosystems has become an increasingly alarming public health concern. Hydrogen peroxide (H2O2) is an important oxidant in nature and the most stable reactive oxygen species occurred in natural water. In order to explore the contribution of free ˙OH generated from H2O2-driven Fenton-like reactions on the degradation of polyethylene (PE) and generation of micro- and nano-scale plastics in water, a batch experiment was conducted over a period of 620 days in water treated with micromolar H2O2. The incorporation of H2O2 in water induced the formation of flake-like micro(nano)-sized particles due to intensified oxidative degradation of PE films. The presence of ˙OH significantly enhanced the generation of both micro- and nano-scale plastics exhibiting a higher proportion of particles in the range of 200–500 nm compared to the Control. Total organic carbon in the H2O2 treated solution was nearly 174-fold higher than that of the Control indicating a substantial liberation of organic compounds due to the oxidative degradation of native carbon chain of PE and subsequent decomposition of its additives. The highly toxic butylated hydroxytoluene detected from the gas chromatography-mass spectrometry (GC-MS) analysis implied the toxicological behavior of secondary micro(nano)plastics influenced by the oxidation and decomposition processes The findings from this study further expand our understanding of the role of ˙OH in degrading PE micro-scale plastics into nanoparticles as an implication of naturally occurring H2O2 in aquatic environments. In the future, further attention should be drawn to the underlying mechanisms of H2O2-driven in-situ Fenton reaction mediated by natural environmental conditions targeting the alternation of light and darkness on the oxidative degradation of plastics.

Applications and Risk Assessments of Ionic Liquids in Chemical and Pharmaceutical Domains: An Updated Overview

Abstract: The objective of this review is to evaluate the toxicological profiles and environmental sustainability of Ionic Liquids for chemical applications. Data from in vitro assays, Danio rerio embryo tests and computational models were herein analyzed. The development and properties of 'green' Ionic Liquids were also assessed. Safety evaluations indicate that Ionic Liquids exhibit various toxicological behaviors, challenging the assumption that they are categorically safe for environmental exposure. 'Green' Ionic Liquids show enhanced biodegradability and lower ecotoxicity but are not universally benign. Some Ionic Liquids present toxicological properties that conflict with being environmentally safe. It is, therefore, essential to conduct comprehensive assessments before deeming them environmentally safe. Lifecycle management strategies incorporating circular economy principles are promising but require further validation and detailed analysis for sustainability confirmation.

Combined cytotoxicity of ZnO nanoparticles and chlorpyrifos in the rainbow trout, Oncorhynchus mikyss, gonadal cell line RTG-2

The toxicity of ZnO nanoparticles (ZnO NPs) in aquatic organisms has been extensively studied, but little information is available on the effects associated with their interaction with other contaminants. In this context, the in vitro effects of co-exposure of chlorpyrifos (CPF) and ZnO NPs on fish-derived cells were investigated. A selection of concentrations was tested in single and binary exposures: CPF (0.312 - 75 mg/L) and ZnO NPs (10 - 100 mg/L). Cytotoxicity was measured using commonly used cellular endpoints: Alamar Blue/CFDA-AM for viability and plasma membrane integrity, NRU for lysosomal disruption and MTT for mitochondrial function. In addition, specific mechanisms of toxicity for CPF and ZnO NPs were tested: acetylcholinesterase (AChE) activity and ROS generation, respectively. AChE was by far the most sensitive assay for single exposure to CPF. There was no concentration-response relationship for ROS after single exposure to ZnO NPs, but 10 mg/L produced significant effects only for this cellular endpoint. Co-exposure of CPF with 10 m/L of ZnO NPs produced significant effects in almost all endpoints tested, which were enhanced by co-exposure with 100 mg/L of ZnO NPs. AChE testing of additional co-exposures with bulk ZnO, together with the application of the Independent Action (IA) prediction model, which allowed us to draw more in-depth conclusions on the toxicological behavior of the mixture. Synergism was observed at 0.625 mg/L CPF concentration and antagonism at 5 mg/L CPF in mixtures containing 100 mg/L of both ZnO NPs and bulk ZnO. However, more cases of synergism between CPF and ZnO NPs occurred at intermediate CPF concentrations, demonstrating that nano-sized particles have a more toxic interaction with CPF than bulk ZnO. Therefore it can be argued that in vitro assays allow the identification of interaction profiles of NP-containing mixtures by achieving multiple endpoints with a large number of concentration combinations.

Effect of Sublethal Concentrations of Metal Nanomaterials on Cell Energy Metabolism.

Metallic nanomaterials (MNMs) are widely used in the medical field because of their photocatalytic, optical, electrical, electronic, antibacterial, and bactericidal properties. Despite the advantages of MNMs, there is a lack of complete understanding of their toxicological behavior and their interactions with cellular mechanisms that determine cell fate. Most of the existing studies are acute toxicity studies with high doses, which is not conducive to understanding the toxic effects and mechanisms of homeostasis-dependent organelles, such as mitochondria, which are involved in many cellular functions. In this study, four types of MNMs were used to investigate the effects of metallic nanomaterials on mitochondrial function and structure. We first characterized the four MNMs and selected the appropriate sublethal concentration for application in cells. Mitochondrial characterization, energy metabolism, mitochondrial damage, mitochondrial complex activity, and expression levels were evaluated using various biological methods. The results showed that the four types of MNMs greatly inhibited mitochondrial function and cell energy metabolism and that the material entering the mitochondria damaged the mitochondrial structure. Additionally, the complex activity of mitochondrial electron transport chains is critical for assessing the mitochondrial toxicity of MNMs, which may serve as an early warning of MNM-induced mitochondrial dysfunction and cytotoxicity.

Unveiling the noxious effect of polystyrene microplastics in aquatic ecosystems and their toxicological behavior on fishes and microalgae.

Microplastic (MP) particles are considered noxious pollutants due to their presence in aquatic habitats at almost every level of the food chain. Thus, the entry of MP particles into marine waterbodies has triggered a common research interest. Until recently, the toxicity of polystyrene towards aquatic creatures in comparison to other polymers has not been widely investigated. This article provides an extensive overview of the occurrence of microplastic particles, the route of polystyrene (PS) in the aquatic ecosystem, the PS properties characterization, and its noxious effects on the aquatic biota, particularly fishes and microalgae. Alarming high levels of polystyrene were found in urban, coastal, and rural surface waters and sediments. The fast-screening technique began with a stereoscope to determine the polystyrene particles' shape, size, and color on the organism. SEM and complemented by micro FTIR or Raman spectroscopy were used to evaluate MP's polymer structures. The findings present evidence suggesting that polystyrene buildup in fish can have long-term and unknown consequences. Meanwhile, the presence of polystyrene on microalgae causes a decrease in chlorophyll concentration and photosynthetic activity, which may disrupt photosynthesis by interfering with the electron characters and leading to the production of reactive oxygen species (ROS).

Cathepsin inhibitors as potent inhibitors against SARS-CoV-2 main protease. In silico molecular screening and toxicity prediction

Since the emergence of the newly identified Coronavirus SARS-COV-2, no targeted therapeutic agents for COVID-19 treatment are available, and effective treatment options remain very limited. Successful crystallization of the SARS-CoV-2 main protease (Mpro, PDB-ID 6LU7) made possible the research on finding its potential inhibitors for the prevention of virus replication. To conduct molecular docking, we selected ten representatives of the Cathepsin inhibitors family as possible ligands with a high potential of binding the active site of SARS-CoV-2 main protease as a potential target. The results of molecular docking studies revealed that Ligand1 and Ligand2, with vina scores -8.8 and -8.7 kcal/mol for Mpro, respectively, were the most effective in binding. In silico prediction of physicochemical and toxicological behavior of assessed ligands approved the possibility of their use in clinical essays against SARS-COVID-19. Keywords: 6lu7, cathepsin inhibitors, COVID19, in silico prediction, main protease, molecular docking, SARS-COV-2

English

Zanthoxylum zanthoxyloides has been used for decades in traditional medicine across West African countries to treat several ailments such as malaria and pain. However, sometimes it is used without information on its toxicity level. This present work aimed to explore the toxicity level of Zanthoxylum zanthoxyloides bark aqueous extract (AZZ) on albino Wistar rats after single and repeated administrations. For the acute toxicity evaluation, a single dose of the extract at 3, 5 and 7.5 g/kg of the extract was administered orally, and the animals were kept under observation for mortality and clinical signs for the first four hours, and then once every day for 14 days. For the sub-acute toxicity evaluation, the extract was administered to the animals orally at doses of 0.5, 0.75 and 1 g/kg daily for 28 days. On the 15th day (acute evaluation) or 29th day (sub-acute evaluation), the animals were weighed and anaesthetized and then blood was collected for haematological and biochemical analysis. Vital organs (liver, kidneys and lungs) were removed and weighed. No mortality or toxicological behavior was observed, and there was no statistically significant difference between the treated and control groups for whole body weight and organ weights. Also, the results showed no statistically significant effects on haematological and biochemical parameters. Thus, AZZ may be considered as nontoxic both after single and repeated administrations. Key words: Zanthoxylum zanthoxyloides, bark extract, toxicity level, clinical signs, Wistar rats, hematology, biochemical parameters.

Nanoparticles based nanosensors: Principles and their applications in active packaging for food quality and safety detection

Recent developments in nanotechnology-driven intelligent and active packaging materials have led to increased safety and contamination recognition in real-time and low cost compared to laborious, time-consuming and expensive conventional methods. Nanoparticle-driven nanosensors play a vital role in qualitative and quantitative estimation of change in environmental and microbial infestation at food manufacturing, processing storage and facilities, thus protecting the interest of all stakeholders, from manufacturers, processors, retailers, and consumers to government agencies. On the other hand, the migration of nanoparticles in the food matrix raises concerns about health risks associated with the toxicological behaviour of migrated nanoparticles. This review is focused on nanoparticles driven nanosensors for applications in packaged food safety and quality.

Morpho-biochemical Responses and Disturbed Redox Homeostasis in Barley Under Benzyl-butyl Phthalate Stress.

The present study is aimed to address the morphometric consequences, yield attributes, and biochemical responses of barley plants under the stress of an endocrine disruptor i.e., benzyl-butyl phthalate (BBP). The morphometric analyses (plant length, dry weight, and net primary productivity) revealed that the inhibition induced by BBP was concentration- and time-dependent. The seed weight and the number of seeds per spike have also significantly declined with an increase in BBP doses. Similarly, BBP exhibited significant alterations over the control in the biochemical indices viz., pigments, sugars, proteins, proline, malonaldehyde, and hydrogen peroxide contents of barley plants. Furthermore, BBP stress negatively influenced the activities of antioxidative enzymes viz., SOD, POD, CAT, APX, and GR of barley with an increase in doses and exposure durations due to the over-produced reactive oxygen species. The uptake and transport of BBP were determined and observed as a responsible cue for these toxicological implications in barley plants under BBP exposure. The correlation of barley plants' morpho-biochemical responses with BBP uptake and transport was also established using Pearson's correlation. Thus, this study indicated the toxicological behavior of meagerly explored phthalate (i.e.,BBP) in the crop plant and these observations can be utilized for the generation of tolerant cultivars.

Differences, links, and roles of microbial and stoichiometric factors in microplastic distribution: A case study of five typical rice cropping regions in China.

Microplastics (MPs), as new pollutants in agroecosystems, have already attracted widespread attention from scientists. However, our understanding of MP geographic distribution and its influencing factors across spatial scales remains poor. Here, a regional-scale field investigation was conducted to assess the distribution characteristic of MPs in five major rice-growing regions of China, and we explored the roles of biological and abiotic factors, especially stoichiometry and microbial influences on MP distribution. MPs were observed in all sampling sites, averaging 6,390 ± 2,031 items⋅kg–1. Sizes less than 0.5 mm and black and transparent MPs dominated. Fiber, classified as one of the MP shapes, occurred most frequently. MP community analysis, firstly used in paddy soil, revealed more black MPs abundance in Henan (HE), more rayon, blue, and other colors MPs in Hunan (HN), more transparent MPs in Tianjing (TJ), and more PE MPs in Heilongjiang (DB). Higher MP community diversity was found in most south paddy soils of this study, due to a broader range of sources. C/N showed a positive relationship with pellet-shaped MP abundance and MPs of size between 2 and 5 mm (P < 0.05). Chao1 index of soil microbial communities was positively correlated with the MP abundance, MPs of size less than 0.5 mm, and fiber abundance. The minimum temperature was positively correlated with MP abundance (P < 0.05), implying the potential effects of the freeze-thaw process might exist. The regression analysis highlighted the important role of population quantity in determining MP abundance (R = 0.421, P = 0.02). This study confirmed the wide distribution of MPs in different soil depths of paddy lands in China and demonstrated that its distribution was influenced by population quantity and environmental variables, such as microbiology. These findings could provide a basis for the toxicological behavior of MPs and the potential risk to human health.

Cytocompatibility of oleic acid modified iron oxide nanoparticles

Our long-term goal is to utilize oleic acid-modified iron oxide (OA-Fe3O4) nanoparticles embedded into a monoglyceride matrix for remote drug release utilizing an alternating magnetic field (AMF). However, the toxicological behavior of OA-Fe3O4 nanoparticles when in contact with biological tissues remains unknown. The size, shape, and surface morphology of OA-Fe3O4 nanoparticles prepared in our laboratory were evaluated using SEM and TEM. These data show that the OA-Fe3O4 nanoparticle preparations do not form aggregates and maintain the expected size and shape. We also used HTB-19, a human mammary tumor cell line, to assay the cytocompatibility of OA-Fe3O4 nanoparticles of different sizes (5, 10, 20, and 30 nm) at varying doses (6.25, 12.5, 25, and 50 µg/mL) using CytoTox-Glo™ cytotoxicity kit and phase-contrast inverted microscopy. These results indicate that there is no appreciable cytotoxicity at the lowest (6.25 µg/mL) concentration. Even the highest (50 µg/mL) concentration used in our study show > 75% cell viability. Microscopic morphological assessment performed using phase-contrast inverted microscopy revealed internalization of the nanoparticles and proliferation of cells in the presence of the OA-Fe3O4 nanoparticles. Taken together, our results show that OA-Fe3O4 nanoparticles are a safe and promising biocompatible excipient for drug delivery.

Physiological responses in Nile tilapia (Oreochromis niloticus) induced by combined stress of environmental salinity and triphenyltin

Triphenyltin (TPT) has attracted considerable attention owing to its vitality, bioaccumulation, and lurking damage. TPT widely exists in complex salinity areas such as estuaries and coastal regions. However, there are few studies on the toxicological behavior of TPT under different salinity. In the study, juvenile Nile tilapia (Oreochromis niloticus) were utilized as model animals to investigate the effects of environmental relevant TPT exposure on the osmoregulation and energy metabolism in gill under different salinity. The results showed that salinity and TPT single or combined exposure affected the morphology of the gill tissue. After TPT exposure, Na+-K+-ATPase (NKA) activity significantly decreased at 0 ppt, while NKA and Ca2+-Mg2+-ATPase (CMA) activities significantly increased at 15 ppt. In addition, significantly higher succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) activities were found in the control fish compared to the TPT-exposed ones at 15 ppt. Quantitative real-time PCR results showed that TPT exposure affected the expression of osmoregulation and energy metabolism-related genes under different salinity. Overall, TPT exposure interfered with osmoregulation and energy metabolism under different salinity. The study will provide reference data for assessing the toxicity of organotin compounds in complex-salinity areas.

The adverse health effects of increasing microplastic pollution on aquatic mammals

Microplastics (MPs), an emerging ubiquitous pollutant in the aquatic ecosystem, pose serious health concerns to the survival of aquatic fauna, especially top predators (e.g., aquatic mammals). It is challenging to investigate the toxicological profile of MPs in aquatic mammals due to their diverse toxicological behaviour, physico-chemical properties, and other technical and ethical issues. This study reviewed the current burden of MPs in the aquatic ecosystem, the occurrence of MPs in the various tissues of aquatic mammals, its composition (heavy metals, pesticides, pathogens), and possible health effects on individual and population levels in aquatic mammals. Aquatic mammals are constantly exposed to MPs directly and indirectly via the food-web. The MPs and a wide range of toxic heavy metals, pesticides, and pathogens added during manufacturing or adsorbed from the surrounding environments are bioaccumulated in aquatic mammals for years. Due to their long life-span and heavy body masses, these pollutants can cause several serious health issues in aquatic mammals that can drastically reduce the population size and ultimately can cause extinction, especially in vulnerable populations. Still today the toxicological profile of MPs and its presence in other deep tissues largely remains unknown in aquatic mammals. We therefore suggest a global assessment of the risks associated with the consumption of MPs by aquatic mammals and the presence of MPs in their habitats.

Polystyrene Nanoplastics Induce Neutrophil Extracellular Traps in Mice Neutrophils.

With growing applications of plastic products, there is a growing threat to human health. Therefore, it is important to understand their toxicological behaviors. The release of neutrophil extracellular traps (NETs) was clarified as a new immune defense mechanism against intruders. Here, we discovered that polystyrene nanoplastics (PS NPs) induce NET formation, with involvement of reactive oxygen species, peptidyl arginine deiminase 4 (PAD4), and neutrophil elastase. Moreover, overexpression of PAD4 induced by PS NPs further mediates histone citrullination and chromatin depolymerization. These results provide important information and promising strategies for safety and immunotoxicity assessment of NPs.