J. Xenobiot., Volume 15, Issue 3 (June 2025) – 30 articles

Imidacloprid, a systemic neonicotinoid insecticide, exerts its neurotoxic effects by binding to nicotinic acetylcholine receptors in the central nervous system. In this study, we examined the effects of commercial imidacloprid formulations on the growth of Chlorella vulgaris and other algal species, comparing these responses with those induced by plant hormones. Our results demonstrate that formulated imidacloprid stimulates C. vulgaris growth at concentrations as low as 7.82 μM, with a more pronounced effect than certain phytohormones. We observed similar growth-enhancing effects in other algal species exposed to imidacloprid. Notably, pure imidacloprid induced equivalent growth responses in C. vulgaris, confirming that the observed stimulation results from the active ingredient itself rather than formulation adjuvants. Given its insecticidal mode of action, potential worst-case aquatic contamination scenarios with imidacloprid may lead to significant increases in algal biomass through both direct (growth stimulation) and indirect (reduction of zooplankton grazing pressure) mechanisms. Full article

In recent years, an increasing number of case reports have mentioned the presence of illicit nootropics, smart drugs or mind doping products on the market. To better understand the extent of the problem, a market surveillance study was organised by the General European Official Medicines Control Laboratory Network and associated member Australia to detect substandard, falsified or illegal medicines or dietary supplements containing unauthorised nootropic molecules of natural or synthetic origin. From January 2020 to September 2024, 159 different samples were documented, which yielded a comprehensive dataset of 166 molecular identification entries. Within this dataset, 34 distinct molecules were identified. Most samples were sold or presented as dietary supplements (49%) or medicines (32%). The vast majority (69%) were collected from the illegal market. Prescription drugs and non-authorised drugs only available on prescription in Russia were found in pharmacological quantities; some of the latter (noopept, phenylpiracetam and phenibut) were intercepted as large bulk quantities of raw material. Unauthorised novel foods, prescription or higher amounts of melatonin, and clinically uncharacterised research molecules were also reported. This study highlights the need for more active monitoring and screening of such products, as consumption of some of the reported samples could have detrimental health effects. Furthermore, as a large number of the samples were presented as dietary supplements, consumers may not be aware of the possible dangers and side-effects of these products. Full article

Phytoremediation using Avena sativa offers a sustainable strategy for mitigating sulfentrazone contamination while integrating bioenergy production. This study proposes an analysis of the bioenergy potential and the microbial metagenomic profile associated with Avena sativa in the presence and absence of sulfentrazone, aiming at the synergistic bioprospecting of microbial communities capable of biodegradation and remediation of contaminated environments. Using a randomized block design, we evaluated the bioenergy potential and rhizospheric microbial dynamics of A. sativa in soils with and without sulfentrazone (600 g ha⁻¹). Herbicide residues were quantified via UHPLC-MS/MS, and metagenomic profiles were obtained through 16S rRNA gene and ITS region sequencing to assess shifts in rhizospheric microbiota. Microbial diversity was analyzed using the Shannon and Gini–Simpson Indices, complemented by Principal Component Analysis (PCA). Bioenergy yields (biogas and ethanol) were estimated based on plant biomass. Over 80 days, the cultivation of A. sativa promoted a 19.7% dissipation of sulfentrazone, associated with rhizospheric enrichment of plant growth-promoting taxa (Bradyrhizobium, Rhodococcus, and Trichoderma), which increased by 68% compared to uncontaminated soils. Contaminated soils exhibited reduced microbial diversity (Gini–Simpson Index = 0.7), with a predominance of Actinobacteria and Ascomycota, suggesting adaptive specialization. Despite herbicide-induced stress (39.3% reduction in plant height and 60% reduction in grain yield), the biomass demonstrated considerable bioenergy potential: 340.6 m³ ha⁻¹ of biogas and 284.4 L ha⁻¹ of ethanol. The findings highlight the dual role of A. sativa in soil rehabilitation and renewable energy systems, supported by plant–microbe synergies. Scalability challenges and regulatory gaps in ecotoxicological assessments were identified, reinforcing the need to optimize microbial consortia and implement region-specific management strategies. These results support the integration of phytoremediation into circular bioeconomy models, balancing ecological recovery with agricultural productivity. Future research should focus on microbial genetic pathways, field-scale validation, and the development of regulatory frameworks to advance this green technology in global soil remediation efforts. Full article

This study evaluates the effects of caffeine (CAF) on the bacteria Aliivibrio fischeri, the microalga Raphidocelis subcapitata, the macrophyte Lemna minor, and the larvae of Chironomus riparius, aiming to understand its environmental impact and contribution to ecological risk assessment. Bioluminescence inhibition in A. fischeri (EC₅₀ = 998.5 mg/L) and growth inhibition in R. subcapitata and L. minor (EC₅₀ = 60.1 mg/L and EC₅₀ = 649.2 mg/L, respectively) were observed. For L. minor, reduced catalase (CAT) activity and non-linear responses in glutathione S-transferases (GSTs) were recorded. No significant changes were observed in proline, malondialdehyde (MDA), and pigment contents. In C. riparius, acute mortality (LC₅₀ = 644.5 mg/L) was observed, and growth was significantly affected after 10 days of CAF exposure (EC₅₀ = 81.62 mg/L for fresh biomass). After 10 days of exposure, there was an increase in CAT activity and thiobarbituric acid reactive substances, with TBARS levels both at concentrations ≥82.64 mg/L, and a decrease in GSTs (92.18 mg/L) and acetylcholinesterase (AChE) (≤62.09 mg/L) activities of C. riparius. The results show that CAF exposure affects organisms’ metabolic and physiological functions, with varying sensitivities among species, potentially leading to ecological disturbances in aquatic ecosystems. The hazardous concentration for 5% of species was 4.42 mg/L. Long-term studies are necessary to understand the risk of caffeine under more realistic scenarios. Full article

Microplastic (MP) contamination affects all environmental media, even in remote, unpopulated regions of the globe. Many studies have addressed this issue under various aspects; however, actual and definitive evidence that MPs are a cause of human health risk in actual environmental conditions has not been provided. MP decomposition generates smaller nanoplastics (NPs) with different properties, closer to engineered nanoparticles than to MP. Their detection is more complex and laborious than MP’s, and, as such, their fate and effects are still poorly studied. Advanced technologies to remove MP/NPs from supply water are being investigated, but current evidence indicates that conventional drinking water treatment facilities efficiently remove a major part of MPs, at least as far as sizes greater than 20 µm. Notwithstanding recent developments in MP/NP classification and detection techniques, at the moment, very few studies specifically address NPs, which, therefore, deserve more targeted investigation. This paper addresses MPs and NPs in drinking water, examining recent current literature on their presence and state-of-the-art in risk assessment and toxicology. The paper also critically overviews treatment technologies for their removal and discusses the present knowledge gap and possible approaches to this widespread issue. Full article

Polycyclic aromatic hydrocarbons (PAHs), prevalent aquatic contaminants, arise from burning fossil fuels, a major source of greenhouse gases driving global warming. PAHs and warmer temperatures individually exert diverse negative effects on aquatic organisms. However, the effects of PAH exposure and/or rising temperature remain largely unknown. Liver in vitro models, like the rainbow trout (Oncorhynchus mykiss) RTL-W1 liver cell line, have been employed to unravel PAH-exposure effects, primarily on cell viability and enzymatic activity. Here, monolayer-cultured (2D) RTL-W1 cells were used to assess the co-exposure effects of temperature (18 and 21 °C) and two PAHs, benzo[a]pyrene (B[a]P) and benzo[k]fluoranthene (B[k]F), at 10 and 100 nM. After a 72 h exposure, the cell density and viability were evaluated using the trypan blue and LDH assays. The mRNA levels of the detoxification-associated genes aryl hydrocarbon receptor (AhR), cytochrome P450 (CYP)1A, CYP3A27, glutathione S-transferase omega 1 (GSTO1), uridine diphosphate–glucuronosyltransferase (UGT), catalase (CAT), and multidrug resistance-associated protein 2 (MRP2) were measured by RT-qPCR. Temperature influenced cell viability and LDH leakage. Both PAHs reduced the cell density and upregulated the mRNA levels of AhR, CYP1A, CYP3A27, and UGT, while GSTO1 and MRP2 were only augmented after the higher B[k]F concentration. Temperature influenced CAT and UGT expression. There was no interaction between temperature and the PAHs. Overall, the results show that B[k]F has more effects on detoxification targets than B[a]P, whereas a temperature increase mildly affects gene expression. The RTL-W1 in 2D seems useful for unravelling not only the liver effects of PAH but also the impact of temperature stress. Full article

Pesticides play an essential role in modern agriculture, yet increasing evidence links their widespread use to neurotoxic effects that contribute to both neurodegenerative and neurodevelopmental disorders. In recent years, new classes of pesticides such as neonicotinoids and pyrethroids have garnered attention due to their potential to disrupt neurodevelopment, even at low exposure levels. Furthermore, emerging evidence underscores the involvement of the gut–brain axis, neuroinflammation, and epigenetic modulation in pesticide-induced neuropathology. This review aims to synthesize these latest advancements while highlighting underexplored mechanisms, thereby offering a comprehensive and current perspective on pesticide-related neurotoxicity. Data from the Rapid Alert System for Food and Feed (RASFF) indicate that several food products include residues of pesticides recognized for their neurotoxic properties. Although environmental exposure levels are lower than those in occupational contexts, the magnitude and persistence of food-based exposure demand thorough evaluation. This review integrates evidence coming from epidemiological, in vivo and in vitro investigations, emphasizing the correlations between pesticide exposure and conditions such as Alzheimer’s disease, Parkinson’s disease, and cognitive deficits in children. Neurodevelopmental toxicity is especially alarming since symptoms may manifest subtly and with a delayed onset after early-life exposure, indicating the significant neurotoxic potential of pesticide residues and emphasizing the need for their careful evaluation in food safety assessments. Improved regulatory procedures and public health efforts are essential to reducing long-term brain damage. Full article

Background: The toxicity of pesticides for fish in general and Rainbow Trout (Oncorhynchus mykiss) in particular is an important ecological indicator required by regulations, and it implies the use of a large number of fish. The number of animals needed would be even higher to evaluate metabolites and pesticide impurities. Considering ethical issues, the costs, and the necessary resources, the use of in silico models is often proposed. Aim of the study: We explore the use of advanced Monte Carlo methods to obtain improved results for models testing Rainbow Trout (Oncorhynchus mykiss) acute toxicity. Several versions of the stochastic Monte Carlo simulation of pesticide toxicity for Rainbow Trout, carried out using CORAL software, were studied. The set of substances was split into four subsets: active training, passive training, calibration, and validation. Modeling was repeated five times to enable better statistical evaluation. To improve the predictive potential of models, the index of ideality of correlation (IIC), correlation intensity index (CII), and coefficient of conformism of correlation prediction (CCCP) were applied. Main results and novelty: The most suitable results were observed in the case of the CCCP-based optimization for SMILES-based descriptors, achieving an R² of 0.88 on the validation set, in all five random splits, demonstrating consistent and robust modeling performance. The relationship of information systems related to QSAR simulation and new ideas is discussed, assigning a key role to fundamental concepts like mass and energy. The study of the mentioned criteria of predictive potential during the conducted computer experiments showed that even though they are all aimed at improving the predictive potential, their values do not correlate, except for the CII and the CCCP. This means that, in general, the information impact of the considered criteria has a different nature, at least in the case of the simulation of toxicity for Rainbow Trout (Oncorhynchus mykiss). The applicability domain of the model is specific for pesticides; the software identifies potential outliers by looking at rare molecular fragments. Full article

The occurrence of per- and polyfluoroalkyl substances (PFASs) in drinking water remains a critical environmental and public health concern. This study examines the presence of both regulated and unregulated PFASs in twenty-one bottled water and twenty-four tap water samples, assessing their concentrations, co-occurrence patterns, and potential human health implications. Regulated PFASs accounted for 87% of total PFASs in bottled water and 92% in tap water, demonstrating the effectiveness of current EU regulations. However, unregulated PFASs were detected in both water sources, contributing to 13% and 8% of total PFAS concentrations in bottled and tap water, respectively. Principal Component Analysis (PCA) and Pearson correlation matrices revealed distinct clustering patterns, suggesting common contamination sources and potential cumulative exposure risks. The presence of emerging PFASs, such as 4:2 FTSA and HFPO-DA, raises concerns about gaps in regulatory oversight, as their long-term health effects remain largely unknown. Despite EU Directive 2020/2184 setting limits on select PFASs, this study highlights the need for expanded monitoring and stricter regulations to address the full spectrum of PFAS contamination. Given the persistence and bioaccumulative nature of these compounds, a comprehensive human health risk assessment is essential to safeguard public health and ensure the safety of drinking water sources. Full article

Antioxidants are widely studied compounds with significant applications in the nutraceutical and dietary industries. To enable the rapid screening of large libraries of substances for antioxidant activity and to provide a useful tool for the initial evaluation of substances of interest with unknown activity, we developed Quantitative Structure–Activity Relationship (QSAR) models to predict the antioxidant potential of chemical substances. We started from a dataset of 1911 antioxidant substances, retrieved from the AODB database by selecting the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity assay and the experimental value of the half-maximal inhibitory concentration. Different machine learning algorithms were applied to build regression models, and the goodness-of-fit of each model was assessed using the statistical parameters of R squared (R²), the Root-Mean-Squared Error, and the Mean Absolute Error. The Extra Trees model outperformed the other models in both internal and external validations, achieving the highest R² of 0.77 and the lowest RMSE on the test set. Gradient Boosting and eXtreme Gradient Boosting also achieved promising results with R² values of 0.76 and 0.75, respectively. Given these results, we developed an integrated method that not only outperformed the individual models, achieving an R² of 0.78 on the external test set, but also provided valuable insights into the range of predicted values. Full article

With the escalating frequency and intensity of global wildfires driven by climate change, fire retardants (FRs) have become essential tools in wildfire management. Despite their widespread use, the environmental safety of newer FR formulations—particularly in relation to aquatic ecosystems and developmental toxicity—remains insufficiently understood. In particular, their effects on fish embryos, which represent a sensitive and ecologically important life stage, are poorly characterized. This study investigated the acute toxicity of three commercially available FRs—N-Borate, N-Phosphate+, and N-Phosphate-—on early life stages of zebrafish (Danio rerio), based on an OECD 236 Fish Embryo Toxicity (FET) test. Notably, N-Phosphate- FR exhibited significant toxicity with a 96 h LC50 of 60 mg/L (0.0055%), while N-Borate (>432 mg/L, >0.032%) and N-Phosphate+ (>1181 mg/L, >0.08%) showed substantially lower toxicity. Sublethal effects, including reduced yolk sac absorption and yolk sac darkening, were observed across all FRs, highlighting potential developmental disruptions. The elevated toxicity of N-Phosphate- FR likely stems from its surfactant content. These findings reveal variations in the acute toxicity of different FR formulations, emphasizing the need for ecotoxicological assessments to guide the selection of safer FRs for wildfire management and to protect aquatic biodiversity. The results highlight the importance of incorporating developmental endpoints in FR risk assessments and provide foundational data for regulatory decisions regarding FR application near aquatic habitats. Further research is necessary to elucidate the mechanisms underlying observed effects and to evaluate cross-species toxicity at environmentally relevant concentrations. Full article

This study analyzed 97 pharmaceuticals in samples of surface water, as well as influent and effluent from various wastewater treatment plants (WWTPs), during winter 2022 and spring 2023. Approximately 40% of the tested compounds were detected, at amounts ranging from below the methods’ detection limits to 5623 ng/L (2-hydroxyibuprofen in surface water) and 12,664 ng/L (caffeine in wastewater). Twelve compounds (acetaminophen, ampicillin, azithromycin, caffeine, fluoxetine, gemfibrozil, 2-hydroxyibuprofen, ibuprofen, ketoprofen, mazindol, naproxen, and salicylic acid) were detected with a 100% frequency in both surface water and wastewater samples. The observed high detection frequency of pharmaceuticals within the nonsteroidal anti-inflammatory drugs/analgesics, antibiotics, and psychiatric drug classes aligns with their high consumption. Caffeine was both the compound with the highest concentration and the most prevalent compound detected. Seasonal differences were observed, with higher concentrations detected during winter. Six of the eleven targeted metabolites and degradation products were detected in at least one sample. Risk quotient assessment revealed potential ecological risks, particularly for atorvastatin, caffeine, carbamazepine, and venlafaxine, exceeding risk thresholds for various trophic levels. The studied WWTPs showed limited removal efficiencies, with some compounds presenting higher concentrations in effluent than in influent, emphasizing the need for enhanced treatment to mitigate micropollutant risks. Full article

Aedes aegypti (Linnaeus, 1762) is Brazil’s primary vector of epidemiologically significant arboviruses such as yellow fever, dengue, Zika, and chikungunya. Despite using conventional chemical control measures, this species has developed resistance to standard chemical insecticides, prompting the search for natural larvicidal compounds. Plant protease inhibitors offer an insecticidal alternative as the primary digestive enzymes in the midgut of Ae. aegypti are proteases (trypsin and chymotrypsin). Ae. aegypti larvae fed with ILTI, a Kunitz-type trypsin inhibitor derived from Inga laurina seeds, at concentrations between 0.03 mg of protein per mL (mgP/mL) and 0.12 mgP/mL, exhibited delayed larval development, with a lethal concentration (LC₅₀) of 0.095 mgP mL⁻¹ of ILTI for 50% of fourth-instar larvae (L₄). The ex vivo assay indicated that ILTI effectively inhibited the activity of larval trypsin, which remained susceptible to the inhibitor. Additionally, molecular modelling and docking studies were conducted to predict the three-dimensional ILTI/enzyme molecular complexes at the atomic level. Therefore, the results demonstrate that ILTI functions as a protease inhibitor in this species, presenting itself as a promising larvicidal tool in the control of Ae. aegypti. Full article

Incessant urbanization and industrialization have resulted in several pollutants being increasingly produced and continuously discharged into the environment, altering its equilibrium, with a high risk for living organisms’ health. To restore it, new advanced materials for remediating gas streams, polluted soil, water, wastewater, groundwater and industrial waste are continually explored. Carbon-based nanomaterials (CNMs), including quantum dots, nanotubes, fullerenes and graphene, have displayed outstanding effectiveness in the decontamination of the environment by several processes. Carbon nanotubes (CNTs), due to their nonpareil characteristics and architecture, when included in absorbents, filter membranes, gas sensors, etc., have significantly improved the efficiency of these technologies in detecting and/or removing inorganic, organic and gaseous xenobiotics and pathogens from air, soil and aqueous matrices. Moreover, CNT-based membranes have displayed significant potential for efficient, fast and low-energy water desalination. However, despite CNTs serving as very potent instruments for environmental detoxification, their extensive utilization could, paradoxically, be highly noxious to the environment and, therefore, humans, due to their toxicity. The functionalization of CNTs (F-CNTs), in addition to further enhancing their absorption capacity and selectivity, has increased their hydrophilicity, thus minimizing their toxicity and carcinogenic effects. In this scenario, this review aims to provide evidence of both the enormous potential of CNTs in sustainable environmental remediation and the concerning hazards to the environment and living organisms that could derive from their extensive and uncontrolled utilization. To this end, an introduction to CNTs, including their eco-friendly production from biomass, is first reported. Several literature reports on CNTs’ possible utilization for environmental remediation, their potential toxicity due to environmental accumulation and the challenges of their regeneration are provided using several reader-friendly tools, to better capture readers’ attention and make reading easier. Full article

Nanoplastic (NP) pollution has emerged as a growing concern due to its potential impact on human health, although its adverse effects on different organ systems are not yet fully understood. This systematic scoping review, conducted in accordance with international guidelines, aimed to map the current evidence on the biological effects of NPs. In vitro animal studies assessing cellular damage caused by exposure to any type of NP were searched on PubMed, Web of Science, and Scopus. Data on primary outcomes related to genotoxicity and cytotoxicity (cell viability, oxidative stress, inflammation, DNA and cytoplasmic damage, apoptosis) were extracted from the included studies, and overall reporting quality was assessed. A total of 108 articles published between 2018 and 2024, mostly by China (54%), Spain (14%), and Italy (9%), were included. Polystyrene (PS) was the most frequently studied polymer (85%). NP sizes in solution ranged from 15 to 531 nm, with a higher prevalence in the 40–100 nm range (38%). The overall quality of studies was rated as moderate (60%), with many lacking essential details about cell culture conditions (e.g., pH of the medium, passage number, substances used). A higher frequency of negative effects from NP exposure was observed in respiratory cell lines, while immune, digestive, and hepatic cell lines showed greater resistance. Nervous, urinary, and connective tissue systems were impacted by NPs. Positively charged and smaller PS particles were consistently associated with higher toxicity across all systems. In summary, this review highlights the multifactorial nature of NP toxicity, influenced by size, surface charge, and polymer type. It also reveals a significant knowledge gap, stemming from the predominant use of immortalized monocultures exposed to commercially available PS NPs, the limited use of environmentally relevant particles, and the underutilization of advanced experimental models (e.g., organ-on-chip systems) that better mimic physiological conditions. Full article

The aim of this study was to measure the concentrations of As, Cd, Hg, Pb, Cr, Cu, Fe and Zn in the muscle, liver and kidney of wild boar (Sus scrofa) in Papuk Nature Park, Eastern Croatia. Muscles, liver and kidney of 38 wild boars, up to 3 years of age, were collected and the concentrations of elements were determined by ICP-MS. Cadmium exceeded the permitted levels acceptable for human consumption in 50% of kidney samples (max. = 6.64 mg kg⁻¹), 20% of liver samples (max. = 4.60 mg kg⁻¹) and 43% of muscle samples (max. = 0.672 mg kg⁻¹). Lead exceeded acceptable levels in 63% of liver samples (max. = 0.463 mg kg⁻¹), 51% of kidney samples (max. = 11.8 mg kg⁻¹) and 65% of muscle samples (max. = 9.10 mg kg⁻¹). Mercury concentrations in the liver were higher than allowed in 13% (max. = 0.552 mg kg⁻¹) in kidneys in 27% (max. = 0.484 mg kg⁻¹), and in the muscles in 15% (max. = 0.103 mg kg⁻¹) of cases. Arsenic concentrations in muscles exceeded the permissible value in 30% of cases (max. = 0.286 mg kg⁻¹). The concentrations of Cr, Cu, Fe and Zn did not significantly differ from the values reported in other studies. Median concentrations of Cr, Cu, Fe and Zn ranged as follows: muscle (0.193, 2.94, 44.5 and 20.6 mg kg⁻¹), kidney (0.140, 5.32, 110 and 23.3 mg kg⁻¹) and liver (0.130, 3.71, 278 and 36.0 mg kg⁻¹). Full article

Genetic predisposition accounts for less than 20% of the global disease burden, highlighting the substantial role of environmental factors in health outcomes. In chronic kidney disease (CKD), a growing global prevalence, understanding the interplay between genes and the environment is crucial. Emerging research in the exposome and genome underscores how environmental exposures interact with genetic variants to influence the development and progression of CKD. The term “exposome” encompasses a variety of factors, including personal behaviors like smoking, a sedentary lifestyle, and making specific dietary choices (such as consuming ultra-processed foods, sugar, or fat). It also includes broader determinants such as pesticides, air, water, and soil pollution, nanoplastics, global warming, stressful life events, and socioeconomic status. Research on the exposome significantly increases our understanding of toxicological processes and individual variations in susceptibility to environmental stressors. This narrative review aims to explore the exposome associated with CKD, highlight key environmental exposures in its development, and discuss potential preventive and therapeutic strategies informed by these exposure-related factors. Full article

Phthalates, a group of synthetic non-persistent organic chemicals commonly used as solvents and plasticisers, have been associated with a range of detrimental health effects. These endocrine disrupting chemicals (ECDs) may exert their effects through epigenetic changes such as altered microRNA (miRNA) expression. miRNAs are short non-coding endogenous RNA transcripts that are preferentially expressed in various tissues and cell types and can circulate in body fluids, thereby regulating gene expression and acting as mediators for intercellular communication. As miRNAs mostly target protein-coding transcripts, they are involved in nearly all networks that regulate developmental and pathological processes. In this review, we provide an overview of human, in vivo and in vitro studies assessing altered miRNA expression due to phthalate exposure and their biological effects. Importantly, this study suggests that the mechanism of phthalate action may in part be mediated by epigenetic changes, affecting a large number of different proteins. This is indicative that alterations in miRNA expression induced by phthalate exposure are then implicated in a wide range of health conditions, including reproductive dysfunction, oncogenesis, metabolic disorders, and neurodevelopmental outcomes. Exposure to phthalates and their metabolites predominantly results in the upregulation of miRNAs. Dysregulation of miR-34a, miR-15b, miR-141, miR-184, miR-19a, miR-125, and miR-let-7 were observed across several studies. More research involving human participants combined with mechanistic studies integrating mRNA target analysis would be beneficial in understanding the downstream effects of phthalate exposure on gene expression and grasping the broader biological implications. Full article

Pituitary adenomas, although predominantly benign, can lead to significant clinical complications due to endocrine imbalances and mass effects on adjacent structures. Traditional research has focused on intrinsic factors like genetic mutations and hormonal dysregulation; however, emerging evidence implicates environmental pollutants—particularly urban air contaminants—in pituitary tumorigenesis. This review consolidates current findings on how chronic exposure to pollutants such as benzene, di(2-ethylhexyl) phthalate (DEHP), and polychlorinated biphenyls (PCBs) may trigger neuroinflammation, disrupt the hypothalamic–pituitary–adrenal (HPA) axis, and alter pituitary cell proliferation and hormone secretion. We explore mechanistic pathways involving inflammatory cytokines, oxidative stress, and microenvironmental modifications that contribute to neoplastic transformation and tumor progression. Epidemiological studies, supported by in vitro experiments, suggest that air pollutants not only initiate the development of pituitary adenomas but may also enhance the secretory activity of functioning tumors, potentially increasing their aggressiveness. Given the escalating global burden of air pollution and its far-reaching public health implications, further investigation is essential to elucidate these complex interactions. Advancing our understanding in this area could inform preventive strategies and therapeutic interventions aimed at mitigating the environmental impact on pituitary tumor behavior. Full article

Heavy metal toxicity leads to impaired crop growth and reduced crop yields and product quality by disrupting plant nutrient uptake, inhibiting development, inducing oxidative stress, and causing cellular toxicity. Arbuscular mycorrhizal fungi (AMF) can play a crucial role in crops’ adaptation to manganese (Mn) toxicity by regulating nutrient uptake and altering subcellular compartmentalization. The present study examines the influence of intact extraradical mycelia (ERMs) from native AMF on wheat (Triticum aestivum) grown in Mn-toxic soil, with a focus on the tissue-specific and subcellular Ca, Mg, P, and Mn distribution. Wheat cultivated in soil pre-colonized using an intact ERM associated with Lolium rigidum or Ornithopus compressus exhibited enhanced growth and improved P contents. During the first week of growth, the Mn concentrations increased in the wheat’s roots and shoots, but Mn was subsequently reduced and sequestered within the cell wall. In contrast, in the absence of an intact ERM, the Mn accumulation in wheat followed an apparent continuous time-course pattern. AMF-mediated cell wall sequestration seems to contribute to Mn detoxification by limiting excessive cytoplasmic accumulation. Furthermore, AMF-driven changes in the element distribution suggest a dynamic response, wherein an early-stage nutrient uptake transitions into a long-term protective mechanism. These findings highlight the potential of AMF in mitigating Mn stress in crops, providing insights for sustainable agriculture and soil remediation strategies. Full article

Retinoic acid (RA), a vitamin A derivative, has been shown to prevent the development of neurological disorders by ensuring the integrity of the physiological structure of the neurovascular unit and regulating the physiological cell’s function. After an ischemia event, RA reduces the effects of blood–brain barrier disruption by blocking the apoptotic signaling pathway. However, the effect of RA on smooth muscle cells (SMCs), which are crucial to maintaining blood perfusion, has never been investigated. This study aimed to evaluate the effect of RA on the vasoactive response of middle cerebral artery SMCs in normal and ischemic contexts (O₂ and glucose deprivation, OGD). For this purpose, SMCs cultures were incubated with RA, and the vasoactive response was evaluated in both conditions (OGD and non-OGD). To simulate OGD, co-cultures of neurons and astrocytes were made and incubated with RA to analyze the effect of the secretome released by these cells on SMCs contractility. In non-OGD conditions, RA induced rapid relaxation of SMCs and, in the long term (24 h), promoted cell contraction. In OGD conditions, SMCs contractility patterns were different when pre-incubated with RA. In these conditions, NA loses its contractility effect, and SNP seems to revert its relaxant effect. However, SMCs pre-incubated with 5 uM RA show the vasorelaxant pattern typical of SNP, despite the OGD condition. These effects demonstrate an effect of RA on the vasoactive profile of SMCs, with therapeutic potential in OGD conditions. Full article

Cardiovascular diseases (CVDs) are the leading cause of mortality globally, accounting for approximately one-third of all deaths. Exposure to toxic metals poses significant risks to cardiovascular health, contributing to the development of CVDs. Essential elements are crucial for maintaining cardiovascular function; however, imbalances or deficiencies in these elements can exacerbate the risk and progression of CVDs. Understanding the interactions between toxic metals and essential elements is crucial for elucidating their impact on cardiovascular health. This study aims to examine the individual and combined effects of toxic metals—lead (Pb), cadmium (Cd), and mercury (Hg)—along with essential elements—manganese (Mn), iron (Fe), and selenium (Se)—on CVDs. We explored the effects of toxic metals and essential elements using data from the National Health and Nutrition Examination Survey (NHANES, 2017–2018). We conducted descriptive analyses and applied advanced statistical methods, including Bayesian kernel machine regression (BKMR), weighted quantile sum regression (WQSR), and quantile g-computation, to assess the associations between these toxic metals and essential elements on key cardiovascular-related biomarkers. The results revealed distinct patterns of influence across the toxic metals and essential elements. Spearman correlation showed a stronger association among toxic metals than essential elements. Bayesian kernel machine regression (BKMR) and posterior inclusion probability (PIP) analysis identified lead, mercury, iron, and selenium as key contributors to CVD risk, with lead strongly linked to high-density lipoprotein (HDL), diastolic blood pressure (DBP), and systolic blood pressure (SBP). Selenium was linked to low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol. Univariate and bivariate analyses confirmed lead and mercury’s strong associations with triglycerides and blood pressure, while lead, selenium, and iron were linked to different cholesterol outcomes. Single-variable analysis revealed an interaction between individual exposures and combined exposures. The overall exposure effect assessing the impact of all exposures combined on CVD markers revealed a steady positive association with triglycerides, total cholesterol, LDL, non-HDL cholesterol, and DBP, with HDL and SBP increasing from the 65th percentile. Quantile g-computation and WQSR confirmed lead’s consistent positive association across all outcomes, with variations among other toxic metals and essential elements. In conclusion, our study suggests that toxic metals and essential elements are important factors in CVD outcomes, with different metals and elements associated with variations in specific biomarkers. Full article

The International Agency for Research on Cancer has studied and classified 1045 potential substances. It is therefore important to develop rapid screening methods to identify the mutagenicity of compounds and, further on, the intensity and number of individual mutagenic substances in complex sample mixtures. The current in vitro Ames assay in the microtiter plate format (MPF) uses a pH-sensitive detection as endpoint, however, acidic substances in complex mixtures may interfere the mutagenicity result. Hence, it was transferred to the planar assay format to be more selective for complex mixture testing. The co-culture of Salmonella Typhimurium strains TA98 and TA100 with an optical density of 0.4 at 600 nm was applied on a high-performance thin-layer chromatography silica gel 60 chromatogram and on-surface incubated for 5 h, which period was limited due to zone diffusion. Various positive controls were tested, and 4-nitrochinolin-N-oxide with a limit of detection of 100 ng was established as a positive control. However, due to the shorter incubation time, no mutagenic compounds were detectable or differentiable in the tested perfumes, herbal teas, margarines, and hand creams. This does not mean that the samples are mutagen-free, but it suggests that further improvements to the bioassay are urgently needed to increase the sensitivity and selectivity of the response. Compared to conventional sum value assays, a planar Ames assay performed on the separated and adsorbed sample components advances toxicology research because mutagenic compounds are separated from interfering molecules due to the integrated separation. It thus would provide a more selective detection of mutagens in complex mixtures and allow testing of large sample volumes or concentrated samples without matrix interference. Full article

Cannabis sativa L. shows potent anti-inflammatory activity, resulting in an interesting pharmacological option for pain management. The aim of the study was to evaluate the association between pharmacogenetics, neurological and inflammatory biomarkers, and cannabinoid plasma exposure in patients treated with cannabis. A total of 58 patients with a diagnosis of neuropathic and chronic pain treated with medical cannabis were analyzed. Cannabis was administered as a decoction (n = 47) and as inhaled cannabis (n = 11): 30 patients were treated with cannabis with high THC, while 28 patients were treated with cannabis with reduced THC (plus CBD). Cannabinoid plasma concentrations were obtained with UHPLC-MS/MS. Allelic discrimination was assessed by real-time PCR. Inflammation biomarkers (e.g., interleukin-10) were analyzed by ELISA, neurofilaments light chain (NFL), and brain-derived neurotrophic factor (BDNF) by Single Molecule Array. A statistically significant difference in IL-10 (p = 0.009) and BDNF (p = 0.004) levels was observed comparing patients treated with decoction and inhaled cannabis. BDNF and NFL results correlated with cannabinoid concentrations. Concerning genetics, the COMT 680 T>C genetic variant influences cannabinoid plasma levels, including Δ9-THC (p = 0.017). Conclusions: This study shows a possible impact of some genetic variants on cannabinoid plasma exposure, other than a possible role of medical cannabis on inflammation-related and neuronal impairment factor levels. Further studies in larger cohorts are required. Full article

Glyphosate based-herbicides are stressors of great concern because they can impact aquatic ecosystems. Similarly, lithium, a metal, is currently of concern because of its increasing use worldwide. Because glyphosate-based herbicides and lithium might co-occur in aquatic environments, there is a need to assess their impacts on aquatic organisms, such as aquatic fungi, as they play a key role in plant litter decomposition in streams. Microcosm assays were used to examine the effects of lithium and the herbicide isopropylammonium glyphosate (IPAG), alone or in mixtures, on microbial leaf mass loss, total fungal sporulation and biomass production. IPAG (alone and combined with LiCl) neither affected plant litter decomposition nor fungal biomass production, but boosted total fungal sporulation. Dimorphospora foliicola, the most tolerant species among the twelfth leaf inhabitant fungal species, is the major contributor to total fungal sporulation. IPAG interacts with LiCl in the total fungal sporulation and sporulation of D. foliicola, A. tetracladia, and F. curvula, indicating a species dependent-effect. IPAG alone or combined with LiCl greatly decreased the diversity of spores, as did as LiCl alone, but to a lesser extent. Finally, aquatic fungal communities reveal redundancy and resiliency to IPAG and LiCL, maintaining the health of aquatic ecosystems. Full article

The excessive intake of monosodium glutamate (MSG) increases its cellular levels in different organs and induces organ toxicity. The current study aims to investigate the metabolic changes and possible causes of hepatic, renal, and cardiac toxicity induced by MSG overconsumption. Thirty adult male rats were randomly allocated into five groups: control, MSG0.8, MSG1, MSG2, and MSG3, which were orally treated with a daily oral dose of saline, 0.8, 1, 2, and 3 g MSG/kg BW, respectively, for eight weeks. The hepatic, renal, and cardiac biochemical markers; lipid profile; glucose; electrolytes; iNOS; α-KGD; oxidative stress; and inflammatory markers were investigated. The histopathological examination of hepatic and renal tissues was also performed. The results revealed MSG-induced hepato-renal and cardiac toxicity, as indicated by the changes in the biochemical markers and tissue architecture of these organs. The toxicity is observed in the form of dyslipidemia, oxidative stress (increased MDA and NO and decreased GSH, SOD, CAT, and GST), and inflammatory responses (increased TNF-α and IL-6). The histopathological changes in liver and kidney architecture confirmed the obtained results. In conclusion, the MSG-induced hepatic, renal, and cardiac toxicity was dose-dependent, and awareness should be raised about the side effects of the overconsumption of MSG. Full article

Decades of technological advancements have led to major environmental concerns, particularly the bioaccumulation of heavy metals, which pose persistent risks to ecosystems and human health. Consequently, research has increasingly shifted from conventional remediation techniques toward more sustainable, environmentally friendly solutions. This review explores recent advancements, ongoing challenges, and future perspectives in the field of bioremediation, emphasizing its potential as a green technology for heavy metal decontamination. Despite significant progress, key challenges remain, including scalability limitations and the management of bioremediation by-products, along with the influence of regulatory policies and public perception on its large-scale implementation. Emerging approaches such as genetic engineering and nanotechnology show promise in overcoming these limitations. Gene editing allows the tailoring of specific metabolic traits for bioprocesses targeted towards increased tolerance to pollutants and higher biodegradation efficiency, higher enzymatic specificity and affinity, and improved yield and fitness in plants. Nanotechnologies, particularly biogenic nanostructures, open up the possibility of repurposing waste materials as well as harnessing the advantages of the biosynthesis of NPs with higher stability, biocompatibility, and biostimulant capacities. Furthermore, biopolymers and bio-based nanocomposites can improve the efficiency and costs of bioremediation protocols. Even so, further research is essential to evaluate their long-term risks and feasibility. Full article

Altered body condition and diminished growth in wildlife in the Alberta Oil Sands Region (AOSR) are prompting investigations into the impact of oil sands industrial activity on wildlife in the region. Chemical constituents from bitumen-influenced waters, including oil sands process-affected water (OSPW), can disrupt endocrine signaling, leading to aberrant lipid accumulation and altered glycemic control in mammals. This study aimed to investigate the effects of naphthenic acid fraction components (NAFCs), derived from OSPW, on energy homeostasis using the McA-RH7777 rat hepatocyte model. Cells were exposed to NAFCs at nominal concentrations of 0, 0.73, 14.7, and 73.4 mg/L for 24 and 48 h. We assessed gene expression related to lipid and glucose metabolism and measured triglyceride accumulation, glucose, and fatty acid uptake. NAFC exposure (14.7 and 73.4 mg/L) reduced triglyceride levels and glucose uptake and increased fatty acid uptake and the expression of beta-oxidation genes, suggesting a metabolic switch from glucose to fatty acid oxidation. This switch in substrate availability signifies a shift in cellular energy dynamics, potentially linked to altered mitochondrial function. To investigate this, we conducted adenosine triphosphate (ATP), mitochondrial membrane potential, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays to measure cellular ATP levels, mitochondrial membrane potential, and apoptosis, respectively. At both time points, 73.4 mg/L NAFC exposure resulted in increased ATP levels, induced mitochondrial membrane hyperpolarization, and increased apoptosis. These results suggest that mitochondrial efficiency is compromised, necessitating metabolic adaptations to maintain energy homeostasis. Given that cells exhibit metabolic flexibility that allows them to dynamically respond to changes in substrate availability, we further demonstrated that the kynurenine–tryptophan ratio (KTR) serves as a marker for a shift in energy metabolism under these stress conditions. This work provides a mechanistic framework for understanding how bitumen-derived organic contaminants may disrupt metabolic function in wildlife living in the AOSR. These findings further support the use of molecular markers like KTR to evaluate sub-lethal metabolic stress in environmental health monitoring. Full article