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J. Xenobiot., Volume 15, Issue 4 (August 2025) – 41 articles

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44 pages, 1673 KiB  
Review
Managing PFAS in Sewage Sludge: Exposure Pathways, Impacts, and Treatment Innovations
by Luoana Florentina Pascu, Valentina Andreea Petre, Ioana Antonia Cimpean, Iuliana Paun, Florinela Pirvu and Florentina Laura Chiriac
J. Xenobiot. 2025, 15(4), 135; https://doi.org/10.3390/jox15040135 - 21 Aug 2025
Abstract
Per- and polyfluoroalkyl substances (PFAS) are a global concern due to their persistence, ubiquity, and accumulation in living organisms. Found in soils, biosolids, water, and the food chain, they pose health risks such as hormone disruption, immune damage, reproductive issues, and cancer. Regulations [...] Read more.
Per- and polyfluoroalkyl substances (PFAS) are a global concern due to their persistence, ubiquity, and accumulation in living organisms. Found in soils, biosolids, water, and the food chain, they pose health risks such as hormone disruption, immune damage, reproductive issues, and cancer. Regulations mainly target older PFAS like PFOA and PFOS, while many newer PFAS, including breakdown products, are poorly understood in terms of distribution, behavior, and toxicity. To address this complex issue, this review offers a detailed overview of human exposure to PFAS and their toxic effects. It highlights biosolids as a key, understudied source of PFAS in the environment. The review also discusses limitations of testing, missing long-term cleanup data, and regulatory issues that neglect total exposure and vulnerable populations. Additionally, it evaluates, in the specific context of biosolids management, the effectiveness, scalability, benefits, and drawbacks of various treatment technologies, such as thermal processes (pyrolysis, incineration, smoldering combustion), advanced oxidation, adsorption, hydrothermal liquefaction, and biological degradation. This work combines environmental science, toxicology, and engineering to outline PFAS management in biosolids and proposes a research and policy plan. Focusing on regulating PFAS as a group, validating real-world results, and employing adaptable treatment strategies underscores the need for a coordinated, science-based effort to reduce PFAS risks worldwide. Full article
(This article belongs to the Section Emerging Chemicals)
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20 pages, 2087 KiB  
Review
Lead Poisoning in the Americas: Sources, Regulations, Health Impacts, and Molecular Mechanisms
by Blanca Miriam Torres-Mendoza, Asbiel Felipe Garibaldi-Ríos, Lourdes Del Carmen Rizo De La Torre, Ana María Puebla-Pérez, Luis E. Figuera, Guillermo Moisés Zúñiga-González, Belinda Claudia Gómez-Meda, Itzae Adonai Gutiérrez-Hurtado, Elvia Harumi Scott-López, Verónica Vázquez-González, Celeste Patricia Gazcón-Rivas and Martha Patricia Gallegos-Arreola
J. Xenobiot. 2025, 15(4), 134; https://doi.org/10.3390/jox15040134 - 20 Aug 2025
Abstract
Lead poisoning is a significant public health issue, contributing to 0.6% of the global disease burden and disproportionately affecting developing countries. Vulnerable populations, such as children, pregnant women, and low-income communities, remain at high risk, often exposed to lead levels exceeding safe thresholds. [...] Read more.
Lead poisoning is a significant public health issue, contributing to 0.6% of the global disease burden and disproportionately affecting developing countries. Vulnerable populations, such as children, pregnant women, and low-income communities, remain at high risk, often exposed to lead levels exceeding safe thresholds. While the problem is global, this review focuses specifically on the Americas, regions with diverse regulatory landscapes and persistent environmental lead exposure. Regulatory frameworks vary widely, and the lack of global consensus on acceptable blood lead levels leaves important gaps in protection. This review compiles and updates knowledge on emerging sources of lead exposure in the region, evaluates advancements in regulatory approaches, and analyzes the molecular impacts of lead on human health. Using the Comparative Toxicogenomics Database (CTD), lead was found to interact with 3448 genes, including those linked to inflammation and oxidative stress, and is associated with 4401 diseases and 799 disrupted pathways. These findings emphasize the need for regionally tailored interventions, strengthened policies, and further research on its health impacts. Full article
(This article belongs to the Topic Environmental Toxicology and Human Health—2nd Edition)
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29 pages, 583 KiB  
Review
Harnessing Engineered Microbial Consortia for Xenobiotic Bioremediation: Integrating Multi-Omics and AI for Next-Generation Wastewater Treatment
by Prabhaharan Renganathan, Lira A. Gaysina, Cipriano García Gutiérrez, Edgar Omar Rueda Puente and Juan Carlos Sainz-Hernández
J. Xenobiot. 2025, 15(4), 133; https://doi.org/10.3390/jox15040133 - 19 Aug 2025
Abstract
The global increase in municipal and industrial wastewater generation has intensified the need for ecologically resilient and technologically advanced treatment systems. Although traditional biological treatment technologies are effective for organic load reduction, they often fail to remove recalcitrant xenobiotics such as pharmaceuticals, synthetic [...] Read more.
The global increase in municipal and industrial wastewater generation has intensified the need for ecologically resilient and technologically advanced treatment systems. Although traditional biological treatment technologies are effective for organic load reduction, they often fail to remove recalcitrant xenobiotics such as pharmaceuticals, synthetic dyes, endocrine disruptors (EDCs), and microplastics (MPs). Engineered microbial consortia offer a promising and sustainable alternative owing to their metabolic flexibility, ecological resilience, and capacity for syntrophic degradation of complex pollutants. This review critically examines emerging strategies for enhancing microbial bioremediation in wastewater treatment systems (WWTS), focusing on co-digestion, biofilm engineering, targeted bioaugmentation, and incorporation of conductive materials to stimulate direct interspecies electron transfer (DIET). This review highlights how multi-omics platforms, including metagenomics, transcriptomics, and metabolomics, enable high-resolution community profiling and pathway reconstructions. The integration of artificial intelligence (AI) and machine learning (ML) algorithms into bioprocess diagnostics facilitates real-time system optimization, predictive modeling of antibiotic resistance gene (ARG) dynamics, and intelligent bioreactor control. Persistent challenges, such as microbial instability, ARG dissemination, reactor fouling, and the absence of region-specific microbial reference databases, are critically analyzed. This review concludes with a translational pathway for the development of next-generation WWTS that integrate synthetic microbial consortia, AI-mediated biosensors, and modular bioreactors within the One Health and Circular Economy framework. Full article
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18 pages, 1185 KiB  
Article
Ecotoxicological Assessment of Sediment Samples Impacted by Wastewater Treatment Plant Effluents Transporting Contaminants of Emerging Concern
by Carlos Silva, Ana Ré, Nelson Abrantes, Fernando J. M. Gonçalves and Joana Luísa Pereira
J. Xenobiot. 2025, 15(4), 132; https://doi.org/10.3390/jox15040132 - 15 Aug 2025
Viewed by 270
Abstract
Wastewater treatment plant (WWTP) effluents can be important sources of contaminants of emerging concern (CEC) for riverine ecosystems, with some accumulation in sediments. This study investigated the ecotoxicological effects of sediment samples collected near three WWTPs. Sediment elutriates, simulating resuspension conditions, and whole [...] Read more.
Wastewater treatment plant (WWTP) effluents can be important sources of contaminants of emerging concern (CEC) for riverine ecosystems, with some accumulation in sediments. This study investigated the ecotoxicological effects of sediment samples collected near three WWTPs. Sediment elutriates, simulating resuspension conditions, and whole sediment samples were tested. Results showed that sediments were toxic to some organisms and beneficial to others. Elutriates from one site significantly reduced luminescence in the bacterium Aliivibrio fischeri, though this was not consistently linked to sediment contaminant levels. Significant noxious effects of elutriates were recorded for the macrophyte Lemma minor (yield reductions up to 48%) and the microalgae Raphidocelis subcapitata (yield reductions up to 25%). Exposure to elutriates resulted in increased Daphnia magna reproduction and increased biomass yield of Chironomus riparius exposed to sediments directly. Overall, there were no major toxicity variations in samples collected upstream and downstream of the effluent outfall. Suggesting limited hazardous potential of the effluent and a potential masking effect of background contamination (mostly metals and polycyclic aromatic hydrocarbons). The complexity of effluent-sourced contamination, coupled with the realistic testing approach, renders this work a valuable contribution to understanding the role of WWTP effluents in surface freshwaters contamination and their effects, especially concerning CECs. Full article
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35 pages, 2122 KiB  
Review
Xenobiotic Toxicants and Particulate Matter: Effects, Mechanisms, Impacts on Human Health, and Mitigation Strategies
by Tamara Lang, Anna-Maria Lipp and Christian Wechselberger
J. Xenobiot. 2025, 15(4), 131; https://doi.org/10.3390/jox15040131 - 14 Aug 2025
Viewed by 359
Abstract
Particulate matter (PM), a complex mixture of solid particles and liquid droplets, originates from both natural sources, such as sand, pollen, and marine salts, and anthropogenic activities, including vehicle emissions and industrial processes. While PM itself is not inherently toxic in all its [...] Read more.
Particulate matter (PM), a complex mixture of solid particles and liquid droplets, originates from both natural sources, such as sand, pollen, and marine salts, and anthropogenic activities, including vehicle emissions and industrial processes. While PM itself is not inherently toxic in all its forms, it often acts as a carrier of xenobiotic toxicants, such as heavy metals and organic pollutants, which adhere to its surface. This combination can result in synergistic toxic effects, significantly enhancing the potential harm to biological systems. Due to its small size and composition, PM can penetrate deep into the respiratory tract, acting as a physical “shuttle” that facilitates the distribution and bioavailability of toxic substances to distant organs. The omnipresence of PM in the environment leads to unavoidable and constant exposure, contributing to increased morbidity and mortality rates, particularly among vulnerable populations like the elderly, children, and individuals with pre-existing health conditions. This exposure also imposes a substantial financial burden on healthcare systems, as treating PM-related illnesses requires significant medical resources and leads to higher healthcare costs. Addressing these challenges necessitates effective mitigation strategies, including reducing PM exposure, improving air quality, and exploring novel approaches such as AI-based exposure prediction and nutritional interventions to protect public health and minimize the adverse effects of PM pollution. Full article
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24 pages, 15698 KiB  
Article
Cardioprotective Effects of SAR Through Attenuating Cardiac-Specific Markers, Inflammatory Markers, Oxidative Stress, and Anxiety in Rats Challenged with 5-Fluorouracil
by Roza Haroon Rasheed and Tavga Ahmed Aziz
J. Xenobiot. 2025, 15(4), 130; https://doi.org/10.3390/jox15040130 - 10 Aug 2025
Viewed by 312
Abstract
This study aimed to evaluate the cardioprotective effects of two different doses of saroglitazar (SAR) in an animal model of cardiotoxicity induced by 5-fluorouracil (5-FU). Thirty-five rats were randomly allocated into five groups: the negative control, which received distilled water; the 5-FU (150 [...] Read more.
This study aimed to evaluate the cardioprotective effects of two different doses of saroglitazar (SAR) in an animal model of cardiotoxicity induced by 5-fluorouracil (5-FU). Thirty-five rats were randomly allocated into five groups: the negative control, which received distilled water; the 5-FU (150 mg/kg as I.P.) group; the N-acetylcysteine (100 mg/kg) group; and the SAR (0.5 and 5 mg/kg) groups. The last three groups received 5-FU on day 10 along with their treatment. An open field test was performed at zero-time and at the end of the study. On day eleven the animals were euthanized and blood samples were used for measuring troponin I, CK-MB, natriuretic peptide, lipid profile, LDH, ALT, AST, CRP, ESR, TNF-α, IL1β, MDA, and total antioxidant capacity (TAOC). Cardiac tissues were sent for histopathological examination. The study revealed that 5-FU elevated the levels of cardiac-specific and injury-related biomarkers, inflammatory and oxidative stress markers, and that the use of SAR, particularly the high dose, decreased all the cardiac- and other injury-related biomarkers as well as attenuating inflammatory and oxidative stress biomarkers. SAR-treated groups exhibited a significant increase in locomotor activity and a decrease in anxiety-like behavior, indicated by a reduction in time spent in one square and an increase in total movement time. Additionally, the histopathological findings greatly supported the biochemical results evidenced by stopping the detrimental effects caused by 5-FU through structural and functional alterations of cardiac tissues manifested as ameliorating congestion, inflammation, degeneration, arterial wall thinning, and endothelial loss. The dual-acting PPAR agonist SAR demonstrated cardiac protection activity, particularly the high dose, by attenuating cardiac-specific and nonspecific injury biomarkers along with anti-inflammatory and antioxidant activities and attenuated anxiety induced by 5-FU. These findings render SAR a promising candidate to be tested in clinical trials. Further studies are warranted with other cardiotoxicants to confirm these findings. Full article
(This article belongs to the Section Drug Therapeutics)
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23 pages, 9644 KiB  
Review
Xenobiotics and Broiler Microbiota: Molecular Insights into Bacterial Antimicrobial Resistance and Food Safety Implications for Human Health
by Marta Gonçalves, Nuno Vale, Paulo Martins da Costa and Paula Silva
J. Xenobiot. 2025, 15(4), 129; https://doi.org/10.3390/jox15040129 - 8 Aug 2025
Viewed by 338
Abstract
Antibiotics have played an evolving role in poultry production, generally transitioning from widespread use to more precise and controlled applications. Despite this shift, the long-term consequences of earlier practices continue to affect current and future generations. This review aims to explore the multifaceted [...] Read more.
Antibiotics have played an evolving role in poultry production, generally transitioning from widespread use to more precise and controlled applications. Despite this shift, the long-term consequences of earlier practices continue to affect current and future generations. This review aims to explore the multifaceted consequences of antibiotic use in poultry production, with particular emphasis on the growing challenge of antimicrobial resistance (AMR). Evidence demonstrates that antibiotic use affects the gut microbiome, often resulting in long-lasting decreased diversity and restructuring of the bacterial communities. Moreover, consequences extend to the surrounding environment, including the airborne microbiome, water systems, and poultry litter, where alterations in microbial communities tend to be more subtle, whereas changes in genetic elements related to resistance are often more pronounced (drift). The emergence and persistence of resistance in these environments facilitate the spread of resistance genes across ecological boundaries, contributing to the broader dissemination of AMR. These findings highlight the complex, interconnected nature of AMR, underscoring the urgent need for responses grounded in the One Health framework. Such approaches are essential for safeguarding both public and environmental health while maintaining sustainable poultry production practices. Full article
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17 pages, 6121 KiB  
Article
The Gut Microbiota Metabolite Urolithin B Mitigates Cholestatic Liver Injury in Mice via Modulating the Crosstalk Between PPARα, Nrf2, and NF-κB Signaling Pathways
by Hani M. Alrawili, Mahmoud Elshal, Marwa S. Serrya and Dina S. El-Agamy
J. Xenobiot. 2025, 15(4), 128; https://doi.org/10.3390/jox15040128 - 8 Aug 2025
Viewed by 362
Abstract
Urolithin (Uro)-B, a gut microbiota metabolite of ellagic acid, has recently gained considerable attention due to its beneficial bioactivities. This study investigated the potential hepatoprotective effect of Uro-B against alpha-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury (CLI) in mice and explored the possible involved [...] Read more.
Urolithin (Uro)-B, a gut microbiota metabolite of ellagic acid, has recently gained considerable attention due to its beneficial bioactivities. This study investigated the potential hepatoprotective effect of Uro-B against alpha-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury (CLI) in mice and explored the possible involved mechanisms. Mice were treated with Uro-B (50 and 100 mg/kg) for four days and received ANIT (75 mg/kg) once on the second day. Our data revealed that Uro-B reduced elevated serum transaminases, alkaline phosphatase, lactate dehydrogenase, and total bilirubin levels associated with ANIT injection. Histopathologically, Uro-B effectively ameliorated ANIT-induced disruption of the hepatic architecture as represented by repressed necro-inflammation and bile duct proliferation. Uro-B also maintained oxidant/antioxidant status that was dysregulated by ANIT. Mechanistically, Uro-B markedly activated Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling with subsequent upregulation of hepatic heme oxygenase-1 expression. On the other hand, Uro-B suppressed the ANIT-induced expression of nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Interestingly, Uro-B repressed peroxisome proliferator-activated receptor alpha (PPARα) expression in the liver. These findings indicate a promising hepatoprotective effect of Uro-B against ANIT-induced CLI in mice. Uro-B modulated the interplay between Keap1/Nrf2, NF-κB/TNF-α, and PPARα signaling pathways, resulting in powerful antioxidant and anti-inflammatory effects. Full article
(This article belongs to the Section Drug Therapeutics)
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21 pages, 3236 KiB  
Article
The Plasticizer Dibutyl Phthalate (DBP) Impairs Pregnancy Vascular Health: Insights into Calcium Signaling and Nitric Oxide Involvement
by Ana R. Quelhas, Melissa Mariana and Elisa Cairrao
J. Xenobiot. 2025, 15(4), 127; https://doi.org/10.3390/jox15040127 - 6 Aug 2025
Viewed by 355
Abstract
Dibutyl phthalate (DBP) is used as a plasticizer to enhance flexibility in several household products, cosmetics, and food-contact materials. Due to its harmful effects, DBP is restricted or banned in children’s products and food items, particularly in Europe. Due to its endocrine disruptor [...] Read more.
Dibutyl phthalate (DBP) is used as a plasticizer to enhance flexibility in several household products, cosmetics, and food-contact materials. Due to its harmful effects, DBP is restricted or banned in children’s products and food items, particularly in Europe. Due to its endocrine disruptor properties and considering its ability to cross the placental barrier, it is imperative to study DBP’s vascular effects in pregnancy, given the vulnerability of this period. Thus, this study investigated the potential effects of DBP on the cardiovascular system using umbilical arteries from healthy pregnant women. Specifically, the impact of DBP on the vascular reactivity after both rapid and 24 h DBP exposure was analyzed, as well as the contractility and the cell viability of vascular smooth muscle cells (VSMC). DBP did not exhibit overt cytotoxic effects on VSMCs, possibly due to its adsorption onto polystyrene surfaces, potentially limiting bioavailability. Interestingly, DBP induced vasorelaxation in a concentration-dependent manner. Although mechanistic insights remain to be fully elucidated, the results suggest the involvement of pathways associated with nitric oxide signaling and calcium handling. Overall, DBP exposure appears to modulate arterial tone regulation, which may have implications for vascular function during pregnancy. Full article
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27 pages, 2559 KiB  
Review
Virgin Coconut Oil and Its Lauric Acid, Between Anticancer Activity and Modulation of Chemotherapy Toxicity: A Review
by Debalina Bose, Adetayo Olorunlana, Rania Abdel-Latif, Ademola C. Famurewa and Eman M. Othman
J. Xenobiot. 2025, 15(4), 126; https://doi.org/10.3390/jox15040126 - 5 Aug 2025
Viewed by 997
Abstract
Virgin coconut oil (VCO) has emerged as a functional food oil with considerable health benefits and wide applications in the food, pharmaceutical, and cosmetic industries due to its resident bioactive compounds, including lauric acid (LA). LA is the most abundant saturated medium-chain fatty [...] Read more.
Virgin coconut oil (VCO) has emerged as a functional food oil with considerable health benefits and wide applications in the food, pharmaceutical, and cosmetic industries due to its resident bioactive compounds, including lauric acid (LA). LA is the most abundant saturated medium-chain fatty acid in VCO and has been associated with several pharmacological activities. The literatures show the pharmacological effects of VCO and LA on chronic pathologies, infectious diseases, and metabolic disorders. A robust body of evidence shows that LA and other phenolic compounds are responsible for the VCO protection against toxicities and pharmacological efficacies. This review elucidates the anticancer mechanisms of VCO/LA and their modulation of the chemotherapy-induced side effect toxicity. VCO, LA, and their nanomaterial/encapsulated derivatives promote ROS generation, antiproliferation, apoptosis, cell cycle arrest, the inhibition of metastasis, and the modulation of cancer-related signaling pathways for cancer cell death in vivo and in vitro. VCO mitigates oxidative inflammation and apoptosis to block the underlying mechanisms of the side effect toxicity of chemotherapy. However, the possible beneficial effect of LA on the toxicity of chemotherapy is currently unknown. The available evidence emphasizes the anticancer effect and mechanism of VCO and LA, and the VCO potential to combat adverse side effects of chemotherapy. Thus, VCO and LA are potential adjuvant therapeutic agents in the management of various cancers. Nevertheless, future studies should be targeted at elucidating cancer-related molecular mechanisms to bridge the gap in knowledge. Full article
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23 pages, 1730 KiB  
Article
Prioritization and Sensitivity of Pesticide Risks from Root and Tuber Vegetables
by Milica Lučić and Antonije Onjia
J. Xenobiot. 2025, 15(4), 125; https://doi.org/10.3390/jox15040125 - 3 Aug 2025
Viewed by 650
Abstract
This study investigated pesticide residues in 580 vegetable samples collected from markets in Serbia, encompassing potatoes, carrots, celery, radishes, horseradish, ginger, onions, and leeks. In total, 33 distinct pesticides were detected using validated HPLC-MS/MS and GC-MS/MS analytical methods. Multiple residues were identified in [...] Read more.
This study investigated pesticide residues in 580 vegetable samples collected from markets in Serbia, encompassing potatoes, carrots, celery, radishes, horseradish, ginger, onions, and leeks. In total, 33 distinct pesticides were detected using validated HPLC-MS/MS and GC-MS/MS analytical methods. Multiple residues were identified in 19 samples, while 29 samples exceeded established maximum residue levels (MRLs). Acute and chronic dietary risks were assessed for both adults and children. Although individual hazard quotients (HQs) for adults and children remained below the threshold of concern (HQ < 1), the cumulative acute risk reached up to 63.1% of the Acute Reference Dose (ARfD) for children and 51.1% ARfD for adults, with ginger and celery posing the highest risks. Similarly, cumulative chronic risks remained below the safety threshold, with the Acceptable Daily Intake (ADI) percentages reaching a maximum of 5.9% ADI for adults and increased vulnerability of 11.0% ADI among children. Monte Carlo simulations were applied to account for variability and uncertainty in chronic exposure estimates. The hazard index (HI) results showed that adverse health effects for both population groups remained within acceptable safety limits (HI < 1), although higher susceptibility was observed in children. Sensitivity analysis identified body weight and vegetable consumption rates as the most influential factors affecting chronic risk variability. Full article
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18 pages, 2003 KiB  
Article
Spatial Gradient Effects of Metal Pollution: Assessing Ecological Risks Through the Lens of Fish Gut Microbiota
by Jin Wei, Yake Li, Yuanyuan Chen, Qian Lin and Lin Zhang
J. Xenobiot. 2025, 15(4), 124; https://doi.org/10.3390/jox15040124 - 3 Aug 2025
Viewed by 359
Abstract
This comprehensive study investigates the spatial distribution of metals in surface water, their accumulation in fish tissues, and their impact on the gut microbiome dynamics of fish in the Qi River, Huanggang City, Hubei Province. Three distinct sampling regions were established: the mining [...] Read more.
This comprehensive study investigates the spatial distribution of metals in surface water, their accumulation in fish tissues, and their impact on the gut microbiome dynamics of fish in the Qi River, Huanggang City, Hubei Province. Three distinct sampling regions were established: the mining area (A), the transition area (B), and the distant area (C). Our results revealed that metal concentrations were highest in the mining area and decreased with increasing distance from it. The bioaccumulation of metals in fish tissues followed the order of gut > brain > muscle, with some concentrations exceeding food safety standards. Analysis of the gut microbiota showed that Firmicutes and Proteobacteria dominated in the mining area, while Fusobacteriota were more prevalent in the distant area. Heavy metal pollution significantly altered the composition and network structure of the gut microbiota, reducing microbial associations and increasing negative correlations. These findings highlight the profound impact of heavy metal pollution on both fish health and the stability of their gut microbiota, underscoring the urgent need for effective pollution control measures to mitigate ecological risks and protect aquatic biodiversity. Future research should focus on long-term monitoring and exploring potential remediation strategies to restore the health of affected ecosystems. Full article
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32 pages, 995 KiB  
Article
Phytotoxic Effects and Agricultural Potential of Nanofertilizers: A Study Using Zeolite, Zinc Oxide, and Titanium Dioxide Under Controlled Conditions
by Ezequiel Zamora-Ledezma, Glenda Leonela Loor Aragundi, Willian Stalyn Guamán Marquines, Michael Anibal Macías Pro, José Vicente García Díaz, Henry Antonio Pacheco Gil, Julián Mauricio Botero Londoño, Mónica Andrea Botero Londoño and Camilo Zamora-Ledezma
J. Xenobiot. 2025, 15(4), 123; https://doi.org/10.3390/jox15040123 - 1 Aug 2025
Viewed by 704
Abstract
Nanofertilizers (NFs) and engineered nanoparticles (NPs) are increasingly used in agriculture, yet their environmental safety remains poorly understood. This study evaluated the comparative phytotoxicity of zinc oxide (ZnO), titanium dioxide (TiO2), and clinoptilolite nanoparticles, three commercial nanofertilizers, and potassium dichromate (K [...] Read more.
Nanofertilizers (NFs) and engineered nanoparticles (NPs) are increasingly used in agriculture, yet their environmental safety remains poorly understood. This study evaluated the comparative phytotoxicity of zinc oxide (ZnO), titanium dioxide (TiO2), and clinoptilolite nanoparticles, three commercial nanofertilizers, and potassium dichromate (K2Cr2O7) using Lactuca sativa seeds under adapted OECD-208 protocol conditions. Seeds were exposed to varying concentrations of each xenobiotic material (0.5–3% for NFs; 10–50% for NPs), with systematic assessment of seedling survival, root and hypocotyl length, dry biomass, germination index (GI), and median effective concentration (EC50) values. Nanofertilizers demonstrated significantly greater phytotoxicity than engineered nanoparticles despite lower application concentrations. The toxicity ranking was established as NF1 > NF3 > NF2 > NM2 > NM1 > NM3, with NF1 being most toxic (EC50 = 1.2%). Nanofertilizers caused 45–78% reductions in root length and 30–65% decreases in dry biomass compared with controls. GI values dropped to ≤70% in NF1 and NF3 treatments, indicating concentration-dependent growth inhibition. While nanofertilizers offer agricultural benefits, their elevated phytotoxicity compared with conventional nanoparticles necessitates rigorous pre-application safety assessment. These findings emphasize the critical need for standardized evaluation protocols incorporating both physiological and ecotoxicological endpoints to ensure safe xenobiotic nanomaterial deployment in agricultural systems. Full article
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22 pages, 2376 KiB  
Review
Hypertension in People Exposed to Environmental Cadmium: Roles for 20-Hydroxyeicosatetraenoic Acid in the Kidney
by Soisungwan Satarug
J. Xenobiot. 2025, 15(4), 122; https://doi.org/10.3390/jox15040122 - 1 Aug 2025
Viewed by 432
Abstract
Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to [...] Read more.
Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to prevent CKD and to reduce its progression to kidney failure is thus of great public health significance. Hypertension is known to be both a cause and a consequence of kidney damage and an eminently modifiable risk factor. An increased risk of hypertension, especially among women, has been linked to chronic exposure to the ubiquitous food contaminant cadmium (Cd). The mechanism is unclear but is likely to involve its action on the proximal tubular cells (PTCs) of the kidney, where Cd accumulates. Here, it leads to chronic tubular injury and a sustained drop in the estimated glomerular filtration rate (eGFR), a common sequela of ischemic acute tubular necrosis and acute and chronic tubulointerstitial inflammation, all of which hinder glomerular filtration. The present review discusses exposure levels of Cd that have been associated with an increased risk of hypertension, albuminuria, and eGFR ≤ 60 mL/min/1.73 m2 (low eGFR) in environmentally exposed people. It highlights the potential role of 20-hydroxyeicosatetraenoic acid (20-HETE), the second messenger produced in the kidneys, as the contributing factor to gender-differentiated effects of Cd-induced hypertension. Use of GFR loss and albumin excretion in toxicological risk calculation, and derivation of Cd exposure limits, instead of β2-microglobulin (β2M) excretion at a rate of 300 µg/g creatinine, are recommended. Full article
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20 pages, 1266 KiB  
Systematic Review
A Systematic Review on Contamination of Marine Species by Chromium and Zinc: Effects on Animal Health and Risk to Consumer Health
by Alexandre Mendes Ramos-Filho, Paloma de Almeida Rodrigues, Adriano Teixeira de Oliveira and Carlos Adam Conte-Junior
J. Xenobiot. 2025, 15(4), 121; https://doi.org/10.3390/jox15040121 - 1 Aug 2025
Viewed by 354
Abstract
Potentially toxic elements, such as chromium (Cr) and zinc (Zn), play essential roles in humans and animals. However, the harmful effects of excessive exposure to these elements through food remain unknown. In this sense, this study aimed to evaluate the anthropogenic contamination of [...] Read more.
Potentially toxic elements, such as chromium (Cr) and zinc (Zn), play essential roles in humans and animals. However, the harmful effects of excessive exposure to these elements through food remain unknown. In this sense, this study aimed to evaluate the anthropogenic contamination of chromium and zinc in aquatic biota and seafood consumers. Based on the PRISMA protocol, 67 articles were selected for this systematic review. The main results point to a wide distribution of these elements, which have familiar emission sources in the aquatic environment, especially in highly industrialized regions. Significant concentrations of both have been reported in different fish species, which sometimes represent a non-carcinogenic risk to consumer health and a carcinogenic risk related to Cr exposure. New studies should be encouraged to fill gaps, such as the characterization of the toxicity of these essential elements through fish consumption, determination of limit concentrations updated by international regulatory institutions, especially for zinc, studies on the influence of abiotic factors on the toxicity and bioavailability of elements in the environment, and those that evaluate the bioaccessibility of these elements in a simulated digestion system when in high concentrations. Full article
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23 pages, 2437 KiB  
Article
From Farmworkers to Urban Residents: Mapping Multi-Class Pesticide Exposure Gradients in Morocco via Urinary Biomonitoring
by Zineb Ben Khadda, Andrei-Flavius Radu, Souleiman El Balkhi, Fagroud Mustapha, Yahya El Karmoudi, Gabriela Bungau, Pierre Marquet, Tarik Sqalli Houssaini and Sanae Achour
J. Xenobiot. 2025, 15(4), 120; https://doi.org/10.3390/jox15040120 - 23 Jul 2025
Viewed by 427
Abstract
Pesticide exposure gradients between occupational, para-occupational, and general populations remain poorly characterized in North African agricultural contexts. This study evaluates urinary pesticide levels among farmers, indirectly exposed individuals, and a control group in Morocco’s Fez-Meknes region. A cross-sectional survey measured pesticide concentrations using [...] Read more.
Pesticide exposure gradients between occupational, para-occupational, and general populations remain poorly characterized in North African agricultural contexts. This study evaluates urinary pesticide levels among farmers, indirectly exposed individuals, and a control group in Morocco’s Fez-Meknes region. A cross-sectional survey measured pesticide concentrations using LC-MS/MS in urine samples collected from 154 adults residing in both rural and urban areas. A questionnaire was used to gather information from participants regarding factors that may elevate the risk of pesticide exposure. The results revealed that farmers exhibited the highest concentrations of pesticides in their urine, including compounds classified as Ia/Ib by the World Health Organization. Indirectly exposed individuals showed moderate levels of contamination, with notable detections such as dichlofluanid (22.13 µg/L), while the control group had residual traces of neonicotinoids, notably imidacloprid (2.05 µg/L). Multivariate analyses revealed several sociodemographic factors significantly associated with increased pesticide exposure. The main risk factors identified included low education, residence in an agricultural area, and the consumption of untreated water (wells/rivers). Conversely, wearing personal protective equipment was associated with reduced urinary concentrations. This study highlights intense occupational exposure among farmers, secondary environmental contamination among residents living near treated areas, and the widespread dispersion of pesticide residues into urban areas. Full article
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22 pages, 1643 KiB  
Article
Skin Wound Healing: The Impact of Treatment with Antimicrobial Nanoparticles and Mesenchymal Stem Cells
by Pavel Rossner, Eliska Javorkova, Michal Sima, Zuzana Simova, Barbora Hermankova, Katerina Palacka, Zuzana Novakova, Irena Chvojkova, Tereza Cervena, Kristyna Vrbova, Anezka Vimrova, Jiri Klema, Andrea Rossnerova and Vladimir Holan
J. Xenobiot. 2025, 15(4), 119; https://doi.org/10.3390/jox15040119 - 18 Jul 2025
Viewed by 537
Abstract
An investigation into the biological mechanisms initiated in wounded skin following the application of mesenchymal stem cells (MSCs) and nanoparticles (NPs) (Ag, ZnO), either alone or combined, was performed in mice, with the aim of determining the optimal approach to accelerate the healing [...] Read more.
An investigation into the biological mechanisms initiated in wounded skin following the application of mesenchymal stem cells (MSCs) and nanoparticles (NPs) (Ag, ZnO), either alone or combined, was performed in mice, with the aim of determining the optimal approach to accelerate the healing process. This combined treatment was hypothesized to be beneficial, as it is associated with the production of molecules supporting the healing process and antimicrobial activity. The samples were collected seven days after injury. When compared with untreated wounded animals (controls), the combined (MSCs+NPs) treatment induced the expression of Sprr2b, encoding small proline-rich protein 2B, which is involved in keratinocyte differentiation, the response to tissue injury, and inflammation. Pathways associated with keratinocyte differentiation were also affected. Ag NP treatment (alone or combined) modulated DNA methylation changes in genes involved in desmosome organization. The percentage of activated regulatory macrophages at the wound site was increased by MSC-alone and Ag-alone treatments, while the production of nitric oxide, an inflammatory marker, by stimulated macrophages was decreased by both MSC/Ag-alone and MSCs+Ag treatments. Ag induced the expression of Col1, encoding collagen-1, at the injury site. The results of the MSC and NP treatment of skin wounds (alone or combined) suggest an induction of processes accelerating the proliferative phase of healing. Thus, MSC-NP interactions are a key factor affecting global mRNA expression changes in the wound. Full article
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42 pages, 8737 KiB  
Review
Environmental Xenobiotics and Epigenetic Modifications: Implications for Human Health and Disease
by Ana Filipa Sobral, Andrea Cunha, Inês Costa, Mariana Silva-Carvalho, Renata Silva and Daniel José Barbosa
J. Xenobiot. 2025, 15(4), 118; https://doi.org/10.3390/jox15040118 - 13 Jul 2025
Viewed by 2843
Abstract
Environmental xenobiotics, including heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, air pollutants, nano- and microplastics, mycotoxins, and phycotoxins, are widespread compounds that pose significant risks to human health. These substances, originating from industrial and agricultural activities, vehicle emissions, and household products, disrupt cellular homeostasis [...] Read more.
Environmental xenobiotics, including heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, air pollutants, nano- and microplastics, mycotoxins, and phycotoxins, are widespread compounds that pose significant risks to human health. These substances, originating from industrial and agricultural activities, vehicle emissions, and household products, disrupt cellular homeostasis and contribute to a range of diseases, including cancer and neurodegenerative diseases, among others. Emerging evidence indicates that epigenetic alterations, such as abnormal deoxyribonucleic acid (DNA) methylation, aberrant histone modifications, and altered expression of non-coding ribonucleic acids (ncRNAs), may play a central role in mediating the toxic effects of environmental xenobiotics. Furthermore, exposure to these compounds during critical periods, such as embryogenesis and early postnatal stages, can induce long-lasting epigenetic alterations that increase susceptibility to diseases later in life. Moreover, modifications to the gamete epigenome can potentially lead to effects that persist across generations (transgenerational effects). Although these modifications represent significant health risks, many epigenetic alterations may be reversible through the removal of the xenobiotic trigger, offering potential for therapeutic intervention. This review explores the relationship between environmental xenobiotics and alterations in epigenetic signatures, focusing on how these changes impact human health, including their potential for transgenerational inheritance and their potential reversibility. Full article
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33 pages, 2301 KiB  
Review
An Integrative Approach to Assessing the Impact of Mercury (Hg) on Avian Behaviour: From Molecule to Movement
by Dora Bjedov, Mirta Sudarić Bogojević, Jorge Bernal-Alviz, Goran Klobučar, Jean-Paul Bourdineaud, K. M. Aarif and Alma Mikuška
J. Xenobiot. 2025, 15(4), 117; https://doi.org/10.3390/jox15040117 - 9 Jul 2025
Viewed by 769
Abstract
Mercury (Hg) pollution is a widespread ecological threat with sublethal effects on wildlife. Birds, due to their ecological diversity and sensitivity, serve as effective models for evaluating the behavioural impacts of Hg exposure. This review applies Tinbergen’s four questions: causation, ontogeny, function, and [...] Read more.
Mercury (Hg) pollution is a widespread ecological threat with sublethal effects on wildlife. Birds, due to their ecological diversity and sensitivity, serve as effective models for evaluating the behavioural impacts of Hg exposure. This review applies Tinbergen’s four questions: causation, ontogeny, function, and evolution, as an integrative framework. Mechanistically, Hg disrupts neuroendocrine pathways, gene expression, immune function, and hormone regulation, leading to behavioural changes such as reduced foraging, altered parental care, and impaired predator avoidance. Early-life exposure affects neural development, learning, and social behaviour into adulthood. Functionally, these changes reduce fitness by compromising reproduction and survival. Phylogenetic comparisons show interspecific variability, with piscivorous and insectivorous birds exhibiting high Hg burdens and sensitivity, linked to ecological roles and exposure. Behavioural responses often precede physiological or demographic effects, highlighting their value as early indicators. Both field and laboratory studies show that even low Hg concentrations can alter behaviour, though outcomes vary by species, life stage, and exposure route. Integrating behavioural endpoints into ecotoxicological risk assessments is essential to improve conservation strategies and understanding of sublethal pollutant effects on wildlife. Full article
(This article belongs to the Section Ecotoxicology)
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17 pages, 4340 KiB  
Article
Butylated Hydroxyanisole (BHA) Disrupts Brain Signalling in Embryo–Larval Stage of Zebrafish Leading to Attention Deficit Hyperactivity Disorder (ADHD)
by Kandhasamy Veshaal, Ramasamy Vasantharekha, Usha Rani Balu, Mahesh Vallabi Aayush, Saheshnu Sai Balaji Pillai, Winkins Santosh and Barathi Seetharaman
J. Xenobiot. 2025, 15(4), 116; https://doi.org/10.3390/jox15040116 - 9 Jul 2025
Viewed by 539
Abstract
Background: Butylated hydroxyanisole (BHA) has been extensively used in several commercial industries as a preservative. It causes severe cellular and neurological damage affecting the developing fetus and might induce attention deficit hyperactivity disorder (ADHD). Methods: Zebrafish embryos were subjected to five distinct doses [...] Read more.
Background: Butylated hydroxyanisole (BHA) has been extensively used in several commercial industries as a preservative. It causes severe cellular and neurological damage affecting the developing fetus and might induce attention deficit hyperactivity disorder (ADHD). Methods: Zebrafish embryos were subjected to five distinct doses of BHA—0.5, 1, 2, 4, and 8 ppb up to 96 h post fertilization (hpf). Hatching rate, heart rate, and body malformations were assessed at 48 hpf, 72 hpf, and 48–96 hpf, respectively. After exposure, apoptotic activity, neurobehavioral evaluation, neurotransmitter assay, and antioxidant activity were assessed at 96 hpf. At 120 hpf, the expression of genes DRD4, COMT, 5-HTR1aa, and BDNF was evaluated by real-time PCR. Results: BHA exposure showed a delay in the hatching rate and a decrease in the heart rate of the embryo when compared with the control. Larvae exhibited developmental deformities such as bent spine, yolk sac, and pericardial edema. A higher density of apoptotic cells was observed in BHA-exposed larvae at 96 hpf. There was a decline in catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and superoxide dismutase (SOD) activity, indicating oxidative stress. There was a significant decrease in Acetylcholinesterase (AChE) activity and serotonin levels with an increase in concentration of BHA, leading to a dose-responsive increase in anxiety and impairment in memory. A significant decrease in gene expression was also observed for DRD4, COMT, 5-HTR1aa, and BDNF. Conclusions: Even at lower concentrations of BHA, zebrafish embryos suffered from developmental toxicity, anxiety, and impaired memory due to a decrease in AChE activity and serotonin levels and altered the expression of the mentioned genes. Full article
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17 pages, 635 KiB  
Article
Environmental Arsenic Exposure, Biomarkers and Lung Function in Children from Yaqui Communities in Sonora, Mexico
by Ana G. Dévora-Figueroa, Anaid Estrada-Vargas, Jefferey L. Burgess, Paloma I. Beamer, José M. Guillen-Rodríguez, Leticia García-Rico, Diana Evelyn Villa-Guillen, Iram Mondaca-Fernández and Maria M. Meza-Montenegro
J. Xenobiot. 2025, 15(4), 115; https://doi.org/10.3390/jox15040115 - 8 Jul 2025
Viewed by 685
Abstract
Arsenic exposure in children and adults has been associated with respiratory symptoms, respiratory infections, and decreased lung function. The goal of this study was to evaluate the relationship between environmental arsenic exposure and serum pneumoproteins and lung function. A cross-sectional study was conducted [...] Read more.
Arsenic exposure in children and adults has been associated with respiratory symptoms, respiratory infections, and decreased lung function. The goal of this study was to evaluate the relationship between environmental arsenic exposure and serum pneumoproteins and lung function. A cross-sectional study was conducted including 175 children exposed to arsenic by drinking water (range: 7.4 to 91 µg/L) and soil (range: 4.76 to 35.93 mg/kg), from some Yaqui villages. Arsenic was analyzed in dust and urine using field-portable X-ray fluorescence spectrometry and ICP/OES, respectively. Serum was analyzed for Clara Cell protein (CC16) and Matrix Metalloproteinase-9 (MMP-9) using immunoassays, and lung function was evaluated by spirometry. The results showed that increased arsenic in drinking water was associated with reduced forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio (β = −0.027, p = 0.0000) whereas, contrary to expectations, arsenic in dust was associated with increased FEV1/FVC (β = 0.004, p = 0.0076). Increased urinary arsenic was associated with reduced % predicted FEV1 (β = −0.723, p = 0.0152) and reduced FEV1/FVC ratio (β = −0.022, p = 0.0222). Increased serum MMP-9 was associated with reduced FEV1/FVC ratio (β = −0.017, p = 0.0167). Children with % predicted FEV1 values less than 80 had the lowest levels of CC16 (Median 29.0 ng/mL, IQR 21.3, 37.4, p = 0.0148). As a conclusion, our study evidenced an impairment in lung function in children exposed to low arsenic levels. Full article
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14 pages, 893 KiB  
Review
Aspartame and Human Health: A Mini-Review of Carcinogenic and Systemic Effects
by Nour El Doueihy, Joya Ghaleb, Karl Kfoury, Katy Kaleen Khouzami, Nicolas Nassif, Philippe Attieh, Hilda E. Ghadieh, Sami Azar, Amjad Kanaan and Frederic Harb
J. Xenobiot. 2025, 15(4), 114; https://doi.org/10.3390/jox15040114 - 7 Jul 2025
Viewed by 2518
Abstract
Aspartame, a widely used artificial sweetener, has been at the center of ongoing debates concerning its safety, particularly its potential role in cancer development. This review provides an overview and analysis of the current research exploring the carcinogenic effects of aspartame. It examines [...] Read more.
Aspartame, a widely used artificial sweetener, has been at the center of ongoing debates concerning its safety, particularly its potential role in cancer development. This review provides an overview and analysis of the current research exploring the carcinogenic effects of aspartame. It examines findings from in vitro studies, in vivo experiments, and epidemiological investigations to offer a comprehensive perspective on the controversy. The results from these studies remain inconsistent—some suggest a possible association between high aspartame intake and increased cancer risk, while others fail to establish a conclusive link. Additionally, this review explores potential mechanisms by which aspartame could exert carcinogenic effects, focusing on its metabolic byproducts and their influence on cellular and molecular processes. Despite these investigations, the question of aspartame’s safety remains unresolved. Continued research is essential to clarify its role in cancer risk and to inform evidence-based dietary guidelines. Full article
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19 pages, 1321 KiB  
Article
Combined Effects of Nano-Polystyrene and Heavy Metal Mixture on the Bioaccumulation of Heavy Metals and Physiological Changes in Macrobrachium rosenbergii
by Mahdi Banaee, Amir Zeidi, Amal Beitsayah, Cristiana Roberta Multisanti and Caterina Faggio
J. Xenobiot. 2025, 15(4), 113; https://doi.org/10.3390/jox15040113 - 7 Jul 2025
Viewed by 636
Abstract
Contaminants such as nano-polystyrenes (NPs) and heavy metal cocktail (HMC) have been found to disrupt physiological functions in aquatic organisms. Although HMC and NPs alone induce oxidative stress, their combined effects are not well understood. This study aimed to assess the combined effects [...] Read more.
Contaminants such as nano-polystyrenes (NPs) and heavy metal cocktail (HMC) have been found to disrupt physiological functions in aquatic organisms. Although HMC and NPs alone induce oxidative stress, their combined effects are not well understood. This study aimed to assess the combined effects of HMC and NPs on the freshwater shrimp (Macrobrachium rosenbergii). Shrimp were divided into seven groups, including the control group, and the experimental groups co-exposed to 0, 50, 100, 150, 200, and 250 µg/L NPs combined with 0.5 mg/L HMC. After 14 days, shrimp were sampled, and their hepatopancreas and muscle tissues were analyzed for oxidative biomarkers, biochemical parameters, and metabolic profiles. Moreover, the bioaccumulation rate of heavy metals was measured. Results showed that co-exposure to NPs and HMC increased superoxide dismutase, glutathione peroxidase, glutathione reductase activities, and malondialdehyde levels, while reducing glutathione and total antioxidant capacity. The integrated biomarker response indicated that co-exposure to HMC and NPs induces oxidative stress. A significant decrease was observed in aspartate aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase activities, glycogen, triglyceride, and total protein levels. However, lactate dehydrogenase activity was significantly increased. Co-exposure to HMC and NPs increased heavy metal bioaccumulation, induced oxidative stress, biochemical changes, and enhanced HMC toxicity in shrimp. Full article
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17 pages, 959 KiB  
Article
Ecotoxicological Effects of Environmentally Relevant Concentrations of Nickel Nanoparticles on Aquatic Organisms from Three Trophic Levels: Insights from Oxidative Stress Biomarkers
by Alberto Teodorico Correia, Eduardo Motta, David Daniel, Bruno Nunes and José Neves
J. Xenobiot. 2025, 15(4), 112; https://doi.org/10.3390/jox15040112 - 4 Jul 2025
Viewed by 535
Abstract
This study investigated the ecotoxicological impacts of environmentally relevant concentrations (0.05, 0.50, and 5.00 mg/L) of nickel nanoparticles (Ni-NPs) by assessing oxidative stress biomarkers. The worm Hediste diversicolor, the bivalve Mytilus spp., and the fish Sparus aurata were chronically exposed to Ni-NPs [...] Read more.
This study investigated the ecotoxicological impacts of environmentally relevant concentrations (0.05, 0.50, and 5.00 mg/L) of nickel nanoparticles (Ni-NPs) by assessing oxidative stress biomarkers. The worm Hediste diversicolor, the bivalve Mytilus spp., and the fish Sparus aurata were chronically exposed to Ni-NPs for 28 days, and glutathione S-transferases (GST), catalase (CAT), and thiobarbituric acid reactive substances (TBARS) levels were measured to evaluate biochemical responses. GST activity increased in H. diversicolor and the liver of S. aurata, suggesting a key role for this enzyme in Ni-NPs detoxification. CAT activity was inhibited in the digestive gland of Mytilus spp. at the highest Ni-NPs concentration, indicating possible disruption of antioxidant defense. TBARS levels rose significantly in the gills of Mytilus spp. exposed to high Ni-NP concentrations, suggesting oxidative damage beyond detoxification capacity. In contrast, TBARS decreased in the digestive gland of Mytilus and in H. diversicolor, possibly due to compensatory upstream antioxidant responses. These findings indicate that each species exhibits distinct adaptive responses to Ni-NP exposure. Overall, this study highlights the need to consider species- and tissue-specific responses when performing ecotoxicological risk assessments of nanomaterials. Full article
(This article belongs to the Special Issue Environmental Toxicology and Animal Health: 2nd Edition)
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24 pages, 1294 KiB  
Review
Effects of Docosahexaenoic Acid on Prostate Cancer
by Guilherme Henrique Tamarindo, Gustavo Matheus Amaro, Alana Della Torre da Silva and Rejane Maira Góes
J. Xenobiot. 2025, 15(4), 111; https://doi.org/10.3390/jox15040111 - 4 Jul 2025
Viewed by 1001
Abstract
The polyunsaturated fatty acids of the omega-3 class have been widely investigated due to their antitumor properties, including in prostate cancer (PCa). Among them is docosahexaenoic acid (DHA, C22:6 ω-3), whose biological activity is higher than other omega-3s, exhibiting a stronger impact on [...] Read more.
The polyunsaturated fatty acids of the omega-3 class have been widely investigated due to their antitumor properties, including in prostate cancer (PCa). Among them is docosahexaenoic acid (DHA, C22:6 ω-3), whose biological activity is higher than other omega-3s, exhibiting a stronger impact on PCa. The specific mechanisms triggered by DHA are blurred by studies that used a blend of omega-3s, delaying the understanding of its biological role, and hence alternative therapeutic approaches. DHA is differentially processed between normal and malignant epithelial PCa cells, which suggests its function as a tumor suppressor. At cell-specific level, it downregulates key pathways in PCa, such as androgen signaling and lipid metabolism, but also changes membrane composition by disrupting phospholipid balance and increasing unsaturation status, arrests the cell cycle, and induces apoptosis and reactive oxygen species (ROS) overproduction. At the tissue level, DHA seems to influence stromal components, such as the inhibition of cancer-associated fibroblast differentiation and resolution of inflammation, which generates a microenvironment favorable to PCa initiation and progression. Considering that such effects are misunderstood and assigned to omega-3s in general, this review aims to discuss the specific effects of DHA on PCa based on in vitro and in vivo evidence. Full article
(This article belongs to the Special Issue Impact of Nutrition and the Environment on Human Metabolism)
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32 pages, 1739 KiB  
Review
Effects of Pharmaceuticals and Endocrine-Disrupting Chemicals on Reproductive Biology of Aquatic Fauna: Penguins as Sentinel Species
by Grace Emily Okuthe, Edith Dube and Patrick Siyambulela Mafunda
J. Xenobiot. 2025, 15(4), 110; https://doi.org/10.3390/jox15040110 - 4 Jul 2025
Viewed by 1080
Abstract
The escalating global contamination of aquatic ecosystems by pharmaceuticals and endocrine-disrupting chemicals (EDCs) stemming from diverse anthropogenic sources represents a critical and pervasive threat to planetary Earth. These contaminants exhibit bioaccumulative properties in long-lived organisms and undergo trophic biomagnification, leading to elevated concentrations [...] Read more.
The escalating global contamination of aquatic ecosystems by pharmaceuticals and endocrine-disrupting chemicals (EDCs) stemming from diverse anthropogenic sources represents a critical and pervasive threat to planetary Earth. These contaminants exhibit bioaccumulative properties in long-lived organisms and undergo trophic biomagnification, leading to elevated concentrations in apex predators. This review synthesizes current knowledge regarding the far-reaching impacts of pharmaceutical and EDC pollution on the reproductive biology of aquatic fauna, focusing on the heightened vulnerability of the endangered African penguin. A rigorous literature review across key scientific databases—PubMed, Scopus, Web of Science, and Google Scholar—using targeted search terms (e.g., penguins, contaminants of emerging concern, penguin species, seabird species, Antarctica, pharmaceuticals, personal care products, EDCs) underpins this analysis. This review explores the anthropogenic sources of pharmaceuticals and EDCs in aquatic ecosystems. It discusses the mechanisms by which these chemicals disrupt the reproductive physiology of aquatic fauna. Recent studies on the ecological and population-level consequences of these contaminants are also reviewed. Furthermore, the review elaborates on the urgent need for comprehensive mitigating strategies to address their effects on vulnerable penguin populations. These approaches hold the potential to unlock innovative pathways for conservation initiatives and the formulation of robust environmental management policies aimed at safeguarding aquatic ecosystems and the diverse life they support. Full article
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21 pages, 1325 KiB  
Article
Antioxidant Potential and Antibacterial Activities of Caucasian Endemic Plants Sempervivum transcaucasicum and Paeonia daurica subsp. mlokosewitschii Extracts and Molecular In Silico Mechanism Insights
by Valentina Mittova, Marina Pirtskhalava, Zurab R. Tsetskhladze, Khatuna Makalatia, Alexander Loladze, Irakli Bebiashvili, Tinatin Barblishvili, Ana Gogoladze and Giovanni N. Roviello
J. Xenobiot. 2025, 15(4), 109; https://doi.org/10.3390/jox15040109 - 4 Jul 2025
Viewed by 1452
Abstract
Antioxidants derived from plant extracts have attracted considerable attention due to their potential in mitigating oxidative damage through free radical scavenging mechanisms. Although 700 species have been used for centuries in Georgian traditional medicine, the chemical composition and antioxidant and antibacterial properties of [...] Read more.
Antioxidants derived from plant extracts have attracted considerable attention due to their potential in mitigating oxidative damage through free radical scavenging mechanisms. Although 700 species have been used for centuries in Georgian traditional medicine, the chemical composition and antioxidant and antibacterial properties of Caucasian endemic medicinal plants remain largely unknown. In this study, the antioxidant and antibacterial activities of leaf and root extracts of Caucasian endemic medicinal plants Sempervivum transcaucasicum Muirhead and Paeonia daurica subsp. mlokosewitschii (Lomakin) D. Y. Hong were investigated. The highest antioxidant activity and phenolic and flavonoid content were revealed in Paeonia daurica leaf extract. The analysis of the content of water-soluble antioxidants revealed the highest content of reduced glutathione and ascorbate in Paeonia daurica leaves. Moreover, the antibacterial activity of leaf and root extracts against Escherichia coli ATCC 25922 strain was investigated, and minimal inhibitory concentration (MIC) values were determined. While the antibacterial activity against E. coli ATCC 25922 was not revealed for the Sempervivum transcaucasicum leaf extract, antibacterial properties were detected for the root extract (MIC 5 mg/mL). Collectively, the highest antibacterial activity was revealed for Paeonia daurica leaf and root extracts (MIC 2 mg/mL and 3 mg/mL, respectively). From a molecular perspective, molecular docking simulations were performed using HDOCK software, with reduced glutathione and ascorbic acid as ligands, in order to analyse their potential binding affinity to the OmpX protein. Inhibiting this protein would likely disrupt bacterial function and produce an antibacterial effect. Our results provide a possible mechanism for the antibacterial activity of Paeonia daurica subsp. mlokosewitschii. Overall, the results of the study demonstrate the potential of Caucasian endemic medicinal plants as natural antioxidants and antimicrobial agents. Full article
(This article belongs to the Special Issue Impact of Nutrition and the Environment on Human Metabolism)
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14 pages, 1682 KiB  
Article
Immobilization of Pleurotus eryngii Laccase via a Protein–Inorganic Hybrid for Efficient Degradation of Bisphenol A as a Potent Xenobiotic
by Sanjay K. S. Patel, Rahul K. Gupta and Jung-Kul Lee
J. Xenobiot. 2025, 15(4), 108; https://doi.org/10.3390/jox15040108 - 3 Jul 2025
Viewed by 477
Abstract
In the present investigation, an eco-friendly biocatalyst was developed using Pleurotus eryngii laccase (PeLac) through a copper (Cu)-based protein–inorganic hybrid system for the degradation of bisphenol A, a representative xenobiotic. After partial purification, the specific activity of crude PeLac was [...] Read more.
In the present investigation, an eco-friendly biocatalyst was developed using Pleurotus eryngii laccase (PeLac) through a copper (Cu)-based protein–inorganic hybrid system for the degradation of bisphenol A, a representative xenobiotic. After partial purification, the specific activity of crude PeLac was 92.6 U/mg of total protein. Immobilization of PeLac as Cu3(PO4)2–Lac (Cu–PeLac) nanoflowers (NFs) at 4 °C resulted in a relative activity 333% higher than that of the free enzyme. The Cu–PeLac NFs exhibited greater pH and temperature stability and enhanced catalytic activity compared to free laccase. This enhanced activity was validated through improved electrochemical properties. After immobilization, Cu–PeLac NFs retained up to 8.7-fold higher residual activity after storage at 4 °C for 30 days. Free and immobilized laccase degraded bisphenol A by 41.6% and 99.8%, respectively, after 2 h of incubation at 30 °C. After ten cycles, Cu–PeLac NFs retained 91.2% degradation efficiency. In the presence of potent laccase inhibitors, Cu–PeLac NFs exhibited a 47.3-fold improvement in bisphenol A degradation compared to free PeLac. Additionally, the synthesized Cu–PeLac NFs demonstrated lower acute toxicity against Vibrio fischeri than Cu nanoparticles. This study presents the first report of PeLac immobilization through an eco-friendly protein–inorganic hybrid system, with promising potential for degrading bisphenol A in the presence of inhibitors to support sustainable development. Full article
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16 pages, 1266 KiB  
Article
A Novel HPLC-MS/MS Method for the Intracellular Quantification of the Active Triphosphate Metabolite of Remdesivir: GS-443902
by Alice Palermiti, Amedeo De Nicolò, Miriam Antonucci, Sara Soloperto, Martina Billi, Alessandra Manca, Jessica Cusato, Giorgia Menegatti, Mohammed Lamorde, Andrea Calcagno, Catriona Waitt and Antonio D’Avolio
J. Xenobiot. 2025, 15(4), 107; https://doi.org/10.3390/jox15040107 - 3 Jul 2025
Viewed by 472
Abstract
Background: Remdesivir (RDV) is a broad-spectrum antiviral prodrug, which is rapidly metabolized in vivo within cells to the pharmacologically active triphosphate metabolite, GS-443902. On the other hand, the dephosphorylated metabolite GS-441524 is the main form detected in plasma. RDV acts against RNA viruses, [...] Read more.
Background: Remdesivir (RDV) is a broad-spectrum antiviral prodrug, which is rapidly metabolized in vivo within cells to the pharmacologically active triphosphate metabolite, GS-443902. On the other hand, the dephosphorylated metabolite GS-441524 is the main form detected in plasma. RDV acts against RNA viruses, and it was the first antiviral drug to receive EMA and FDA approval for treating COVID-19. Nevertheless, its intracellular pharmacokinetics in real life are poorly explored, particularly due to technical challenges. Methods: The aim of this study was to validate an HPLC-MS/MS method for the direct quantification of GS-443902 in peripheral blood mononuclear cells (PBMCs) with a chromatographic separation of 15 min. Results: The method was validated following EMA and FDA guidelines in terms of sensitivity, specificity, accuracy, precision, matrix effect, recovery, carryover, and stability, and then applied to PBMC isolates from a small cohort of patients with severe COVID-19 who received RDV. Conclusions: This work represents the first method for the direct quantification of GS-443902 in PBMCs, with possible future application to intracellular pharmacokinetic studies in different scenarios, such as new oral prodrugs or drug–drug interaction studies. Full article
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19 pages, 3549 KiB  
Article
Oxidative Stress, Phytochemical Screening, and Antioxidant Activity on Microalgae (Arthrospira platensis) After Exposure to Glyphosate and Microplastics
by Dércia Santos, Edna Cabecinha, Jesús Gago, Sandra Mariza Monteiro and Ana Luzio
J. Xenobiot. 2025, 15(4), 106; https://doi.org/10.3390/jox15040106 - 3 Jul 2025
Viewed by 708
Abstract
The knowledge about the potential toxic effects of microplastics (MPs) combined with herbicides at lower trophic levels is still largely unknown. The present study aimed to evaluate the potential toxic effects of polyethylene terephthalate (PET) and polyamide (PA), isolated or combined with the [...] Read more.
The knowledge about the potential toxic effects of microplastics (MPs) combined with herbicides at lower trophic levels is still largely unknown. The present study aimed to evaluate the potential toxic effects of polyethylene terephthalate (PET) and polyamide (PA), isolated or combined with the pesticide glyphosate (GLY), on the microalgae Arthrospira platensis. For this, microalgae were exposed to control, GLY (3 μg/L), PET (0.5 and 1 mg/L), PA (0.5 and 1 mg/L), and the respective mixtures of each MP with GLY, for 12 days. The photosynthetic pigment content, phytochemicals, antioxidants, and enzymatic activity were determined. Cell growth was significantly enhanced on day 4 in the GLY+PA1 group (~80%), compared to the control. At day 12, biomass was significantly higher in the GLY (~25%) and GLY+PET0.5 (~26%) groups relative to the control. Significant effects on the enzymatic and detoxification mechanisms were observed, including increased SOD (PET0.5, p = 0.011) and CarE (GLY, PA and GLY+PA, p < 0.01), and decreased GST in combined exposures, which support stress-induced enzymatic activation and adaptive biochemical responses. Significant effects on phytochemicals and antioxidant activity were also observed, with PET0.5 significantly reducing total carotenoids (~65%), and flavonoids (p < 0.001) and ortho-diphenols (p < 0.05) being decreased in all exposure groups, in comparison to the control group. The decrease in flavonoids and ortho-diphenols, important antioxidant molecules, suggests the depletion of these key compounds under stress. DPPH scavenging activity, a measure of antioxidant potential, was inhibited in the GLY+PA groups, indicating compromised antioxidant defense. Results confirmed that combined stressors elicit distinct and sometimes deleterious responses not predicted by single exposures. Our findings highlight that the combined exposure to glyphosate and MPs significantly disrupts antioxidant defenses and enzymatic activity in A. platensis, indicating potential risks to primary producers in aquatic ecosystems and underscoring the ecological implications of co-contaminant stressors. In fact, the results indicate that MPs can modify herbicide toxicity, posing enhanced risks to microalgal physiology and potentially affecting primary productivity and nutrient cycling in aquatic ecosystems. In turn, negative effects of MPs on microalgae can have serious consequences for food webs, food security, and ecological health. Full article
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