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Keywords = toxicological studies

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20 pages, 4870 KiB  
Article
Histological and Immunohistochemical Evidence in Hypothermia-Related Death: An Experimental Study
by Emina Dervišević, Nina Čamdžić, Edina Lazović, Adis Salihbegović, Francesco Sessa, Hajrudin Spahović and Stefano D’Errico
Int. J. Mol. Sci. 2025, 26(15), 7578; https://doi.org/10.3390/ijms26157578 (registering DOI) - 5 Aug 2025
Abstract
Hypothermia-related deaths present significant diagnostic challenges due to non-specific and often inconsistent autopsy findings. This study investigated the histological and immunohistochemical alterations associated with primary and secondary hypothermia in an experimental Rattus norvegicus model, focusing on the effects of benzodiazepine and alcohol ingestion. [...] Read more.
Hypothermia-related deaths present significant diagnostic challenges due to non-specific and often inconsistent autopsy findings. This study investigated the histological and immunohistochemical alterations associated with primary and secondary hypothermia in an experimental Rattus norvegicus model, focusing on the effects of benzodiazepine and alcohol ingestion. Twenty-one male rats were divided into three groups: control (K), benzodiazepine-treated (B), and alcohol-treated (A). After two weeks of substance administration, hypothermia was induced and multiple organ samples were analyzed. Histologically, renal tissue showed hydropic and vacuolar degeneration, congestion, and acute tubular injury across all groups, with no significant differences in E-cadherin expression. Lung samples revealed congestion, emphysema, and hemorrhage, with more pronounced vascular congestion in the alcohol and benzodiazepine groups. Cardiac tissue exhibited vacuolar degeneration and protein denaturation, particularly in substance-exposed animals. The spleen showed preserved architecture but increased erythrocyte infiltration and significantly elevated myeloperoxidase (MPO)-positive granulocytes in the intoxicated groups. Liver samples demonstrated congestion, focal necrosis, and subcapsular hemorrhage, especially in the alcohol group. Immunohistochemical analysis revealed statistically significant differences in MPO expression in both lung and spleen tissues, with the highest levels observed in the benzodiazepine group. Similarly, CK7 and CK20 expression in the gastroesophageal junction was significantly elevated in both alcohol- and benzodiazepine-treated animals compared to the controls. In contrast, E-cadherin expression in the kidney did not differ significantly among the groups. These findings suggest that specific histological and immunohistochemical patterns, particularly involving pulmonary, cardiac, hepatic, and splenic tissues, may help differentiate primary hypothermia from substance-related secondary hypothermia. The study underscores the value of integrating toxicological, histological, and molecular analyses to enhance the forensic assessment of hypothermia-related fatalities. Future research should aim to validate these markers in human autopsy series and explore additional molecular indicators to refine diagnostic accuracy in forensic pathology. Full article
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23 pages, 9844 KiB  
Article
Mechanistic Exploration of Aristolochic Acid I-Induced Hepatocellular Carcinoma: Insights from Network Toxicology, Machine Learning, Molecular Docking, and Molecular Dynamics Simulation
by Tiantaixi Tu, Tongtong Zheng, Hangqi Lin, Peifeng Cheng, Ye Yang, Bolin Liu, Xinwang Ying and Qingfeng Xie
Toxins 2025, 17(8), 390; https://doi.org/10.3390/toxins17080390 - 5 Aug 2025
Abstract
This study explores how aristolochic acid I (AAI) drives hepatocellular carcinoma (HCC). We first employ network toxicology and machine learning to map the key molecular target genes. Next, our research utilizes molecular docking to evaluate how AAI binds to these targets, and finally [...] Read more.
This study explores how aristolochic acid I (AAI) drives hepatocellular carcinoma (HCC). We first employ network toxicology and machine learning to map the key molecular target genes. Next, our research utilizes molecular docking to evaluate how AAI binds to these targets, and finally confirms the stability and dynamics of the resulting complexes through molecular dynamics simulations. We identified 193 overlapping target genes between AAI and HCC through databases such as PubChem, OMIM, and ChEMBL. Machine learning algorithms (SVM-RFE, random forest, and LASSO regression) were employed to screen 11 core genes. LASSO serves as a rapid dimension-reduction tool, SVM-RFE recursively eliminates the features with the smallest weights, and Random Forest achieves ensemble learning through decision trees. Protein–protein interaction networks were constructed using Cytoscape 3.9.1, and key genes were validated through GO and KEGG enrichment analyses, an immune infiltration analysis, a drug sensitivity analysis, and a survival analysis. Molecular-docking experiments showed that AAI binds to each of the core targets with a binding affinity stronger than −5 kcal mol−1, and subsequent molecular dynamics simulations verified that these complexes remain stable over time. This study determined the potential molecular mechanisms underlying AAI-induced HCC and identified key genes (CYP1A2, ESR1, and AURKA) as potential therapeutic targets, providing valuable insights for developing targeted strategies to mitigate the health risks associated with AAI exposure. Full article
(This article belongs to the Section Plant Toxins)
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20 pages, 4576 KiB  
Article
Physical, Chemical, Mineralogical, and Toxicological Characterization of Active and Inactive Tailings in the Arequipa Region, Peru
by Dery Castillo, Karol Palma, Lizbeth Santander, Héctor Bolaños, Gregorio Palma and Patricio Navarro
Minerals 2025, 15(8), 830; https://doi.org/10.3390/min15080830 (registering DOI) - 5 Aug 2025
Abstract
Mining activity in Peru generates environmental liabilities with the potential to release toxic metals into the environment. This study conducted a comprehensive physical, chemical, mineralogical, and toxicological characterization of ten active and inactive tailings samples from the Arequipa region in southern Peru. Particle [...] Read more.
Mining activity in Peru generates environmental liabilities with the potential to release toxic metals into the environment. This study conducted a comprehensive physical, chemical, mineralogical, and toxicological characterization of ten active and inactive tailings samples from the Arequipa region in southern Peru. Particle size distribution analysis, inductively coupled plasma atomic emission spectroscopy (ICP-AES), scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS), and the Toxicity Characteristic Leaching Procedure (TCLP) followed by ICP-MS were employed. The results revealed variable particle size distributions, with the sample of Secocha exhibiting the finest granulometry. Chemically, 8 out of 10 samples exhibited concentrations of at least two metals surpassing the Peruvian Environmental Quality Standards (EQS) for soils with values reaching >6000 mg/kg of arsenic (Paraiso), 193.1 mg/kg of mercury (Mollehuaca), and 2309 mg/kg of zinc (Paraiso). Mineralogical analysis revealed the presence of sulfides such as arsenopyrite, cinnabar, galena, and sphalerite, along with uraninite in the Otapara sample. In the TCLP tests, 5 out of 10 samples released at least two metals exceeding the environmental standards on water quality, with concentrations up to 0.401 mg/L for mercury (Paraiso), 0.590 mg/L for lead (Paraiso), and 9.286 mg/L for zinc (Kiowa Cobre). These results demonstrate elevated levels of Potentially Toxic Elements (PTEs) in both solid and dissolved states, reflecting a critical geochemical risk in the evaluated areas. Full article
(This article belongs to the Section Environmental Mineralogy and Biogeochemistry)
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15 pages, 1624 KiB  
Article
Cytotoxicity Evaluation of Cyprodinil, Potentially Carcinogenic Chemical Micropollutant, for Oxidative Stress, Apoptosis and Cell Membrane Interactions
by Agata Jabłońska-Trypuć, Nina Wiśniewska, Gabriela Sitko, Urszula Wydro, Elżbieta Wołejko, Rafał Krętowski, Monika Naumowicz, Joanna Kotyńska, Marzanna Cechowska-Pasko, Bożena Łozowicka, Piotr Kaczyński and Adam Cudowski
Appl. Sci. 2025, 15(15), 8631; https://doi.org/10.3390/app15158631 (registering DOI) - 4 Aug 2025
Abstract
Fungicides are compounds with potentially toxic effects on the human body, but the molecular mechanisms of their action have not yet been explained. The effect of cyprodinil on cell viability, apoptosis level, cell membrane function, cell morphology and expression of antioxidant enzyme genes [...] Read more.
Fungicides are compounds with potentially toxic effects on the human body, but the molecular mechanisms of their action have not yet been explained. The effect of cyprodinil on cell viability, apoptosis level, cell membrane function, cell morphology and expression of antioxidant enzyme genes in the A-375 and DLD-1 cell lines was examined. The cell lines were selected because they can be an excellent in vitro model of neoplastic changes occurring in the skin and large intestine after exposure to a fungicide. The fungicide selected for the study is commonly used in Poland to protect crops against fungi. Our results showed that the tested compound increased cell viability and proliferation, probably activated by mechanisms related to oxidative stress. Cyprodinil caused an increase in glutathione level (in A-375 by about 37% and in DLD-1 by about 28%) and oxidative stress enzymes activity, but not in apoptosis level. Its membrane interactions and its penetration into cells was concentration dependent. It is worth emphasizing that the novelty of our work lies in the use of non-traditional toxicological methods based on molecular analyses using human cell lines. This allowed us to demonstrate not only the toxicity of a single substance but also its behavior within cellular structures. Our findings suggest that cyprodinil may have tumor-promoting properties in skin and colorectal cancer cells. Full article
(This article belongs to the Special Issue Exposure Pathways and Health Implications of Environmental Chemicals)
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14 pages, 1969 KiB  
Article
Perfluoroalkyl Substance (PFAS) Mixtures Drive Rheumatoid Arthritis Risk Through Immunosuppression: Integrating Epidemiology and Mechanistic Evidence
by Yanming Lv, Chunlong Zhao, Yi Xiang, Wenhao Fu, Jiaqi Li, Fan Wang and Xueting Li
Int. J. Mol. Sci. 2025, 26(15), 7518; https://doi.org/10.3390/ijms26157518 (registering DOI) - 4 Aug 2025
Abstract
Perfluoroalkyl substances (PFASs) possess immunosuppressive properties. However, their association with rheumatoid arthritis (RA) risk remains inconclusive across epidemiological studies. This study integrates population-based and mechanistic evidence to clarify the relationship between PFAS exposure and RA. We analyzed 8743 U.S. adults from the NHANES [...] Read more.
Perfluoroalkyl substances (PFASs) possess immunosuppressive properties. However, their association with rheumatoid arthritis (RA) risk remains inconclusive across epidemiological studies. This study integrates population-based and mechanistic evidence to clarify the relationship between PFAS exposure and RA. We analyzed 8743 U.S. adults from the NHANES (2005–2018), assessing individual and mixed exposures to PFOA, PFOS, PFNA, and PFHxS using multivariable logistic regression, Bayesian kernel machine regression, quantile g-computation, and weighted quantile sum models. Network toxicology and molecular docking were utilized to identify core targets mediating immune disruption. The results showed that elevated PFOA (OR = 1.63, 95% CI: 1.41–1.89), PFOS (OR = 1.41, 1.25–1.58), and PFNA (OR = 1.40, 1.20–1.63) levels significantly increased RA risk. Mixture analyses indicated a positive joint effect (WQS OR = 1.06, 1.02–1.10; qgcomp OR = 1.26, 1.16–1.38), with PFOA as the primary contributor. Stratified analyses revealed stronger effects in females (PFOA Q4 OR = 3.75, 2.36–5.97) and older adults (≥60 years). Core targets included EGFR, SRC, TP53, and CTNNB1. PFAS mixtures increase RA risk, dominated by PFOA and modulated by sex/age. These findings help reconcile prior contradictions by identifying key molecular targets and vulnerable subpopulations, supporting regulatory attention to PFAS mixture exposure. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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20 pages, 1773 KiB  
Article
Make Acetylcholine Great Again! Australian Skinks Evolved Multiple Neurotoxin-Proof Nicotinic Acetylcholine Receptors in Defiance of Snake Venom
by Uthpala Chandrasekara, Marco Mancuso, Glenn Shea, Lee Jones, Jacek Kwiatkowski, Dane Trembath, Abhinandan Chowdhury, Terry Bertozzi, Michael G. Gardner, Conrad J. Hoskin, Christina N. Zdenek and Bryan G. Fry
Int. J. Mol. Sci. 2025, 26(15), 7510; https://doi.org/10.3390/ijms26157510 (registering DOI) - 4 Aug 2025
Abstract
Many vertebrates have evolved resistance to snake venom as a result of coevolutionary chemical arms races. In Australian skinks (family Scincidae), who often encounter venomous elapid snakes, the frequency, diversity, and molecular basis of venom resistance have been unexplored. This study investigated the [...] Read more.
Many vertebrates have evolved resistance to snake venom as a result of coevolutionary chemical arms races. In Australian skinks (family Scincidae), who often encounter venomous elapid snakes, the frequency, diversity, and molecular basis of venom resistance have been unexplored. This study investigated the evolution of neurotoxin resistance in Australian skinks, focusing on mutations in the muscle nicotinic acetylcholine receptor (nAChR) α1 subunit’s orthosteric site that prevent pathophysiological binding by α-neurotoxins. We sampled a broad taxonomic range of Australian skinks and sequenced the nAChR α1 subunit gene. Key resistance-conferring mutations at the toxin-binding site (N-glycosylation motifs, proline substitutions, arginine insertions, changes in the electrochemical state of the receptor, and novel cysteines) were identified and mapped onto the skink organismal phylogeny. Comparisons with other venom-resistant taxa (amphibians, mammals, and reptiles) were performed, and structural modelling and binding assays were used to evaluate the impact of these mutations. Multiple independent origins of α-neurotoxin resistance were found across diverse skink lineages. Thirteen lineages evolved at least one resistance motif and twelve additional motifs evolved within these lineages, for a total of twenty-five times of α-neurotoxic venoms resistance. These changes sterically or electrostatically inhibit neurotoxin binding. Convergent mutations at the orthosteric site include the introduction of N-linked glycosylation sites previously known from animals as diverse as cobras and mongooses. However, an arginine (R) substitution at position 187 was also shown to have evolved on multiple occasions in Australian skinks, a modification previously shown to be responsible for the Honey Badger’s iconic resistance to cobra venom. Functional testing confirmed this mode of resistance in skinks. Our findings reveal that venom resistance has evolved extensively and convergently in Australian skinks through repeated molecular adaptations of the nAChR in response to the enormous selection pressure exerted by elapid snakes subsequent to their arrival and continent-wide dispersal in Australia. These toxicological findings highlight a remarkable example of convergent evolution across vertebrates and provide insight into the adaptive significance of toxin resistance in snake–lizard ecological interactions. Full article
(This article belongs to the Section Biochemistry)
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16 pages, 7088 KiB  
Article
The Potential Mechanisms of Ochratoxin A in Prostate Cancer Development: An Integrated Study Combining Network Toxicology, Machine Learning, and Molecular Docking
by Hong Cai, Dandan Shen, Xiangjun Hu, Hongwei Yin and Zhangren Yan
Toxins 2025, 17(8), 388; https://doi.org/10.3390/toxins17080388 - 4 Aug 2025
Abstract
Ochratoxin A (OTA), a prevalent food contaminant, has been proposed as a potential contributor to the development of prostate cancer, although its precise mechanisms remain unclear. This study employed a comprehensive approach that integrated network toxicology, machine learning, and molecular docking to clarify [...] Read more.
Ochratoxin A (OTA), a prevalent food contaminant, has been proposed as a potential contributor to the development of prostate cancer, although its precise mechanisms remain unclear. This study employed a comprehensive approach that integrated network toxicology, machine learning, and molecular docking to clarify the role of OTA in prostate cancer. The findings indicated that OTA interacts with 364 targets related to prostate cancer, and machine learning was employed to identify five key molecular targets as priorities (ESR1, TP53, TNF, INS, and EGFR). In conjunction with the results of a functional enrichment analysis, OTA was found to possibly facilitate cancer progression by disrupting endocrine function, activating oncogenic signaling pathways, reprogramming metabolism, and modulating the tumor microenvironment. Full article
(This article belongs to the Section Mycotoxins)
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17 pages, 1724 KiB  
Article
Effects of Eriobotrya japonica (Thunb.) Lindl. Leaf Extract on Zebrafish Embryogenesis, Behavior, and Biochemical Pathways
by Jorge Barros, Irene Gouvinhas, Carlos Venâncio, Daniel Granato, Ana Novo Barros and Luís Félix
Molecules 2025, 30(15), 3252; https://doi.org/10.3390/molecules30153252 - 3 Aug 2025
Viewed by 60
Abstract
Eriobotrya japonica (Thunb.) Lindl. leaves are rich in polyphenolic compounds, yet their toxicological effects in aquatic models remain poorly understood. This study evaluated the impact of a hydroethanolic E. japonica leaf extract on zebrafish embryos through the use of morphological, behavioral, and biochemical [...] Read more.
Eriobotrya japonica (Thunb.) Lindl. leaves are rich in polyphenolic compounds, yet their toxicological effects in aquatic models remain poorly understood. This study evaluated the impact of a hydroethanolic E. japonica leaf extract on zebrafish embryos through the use of morphological, behavioral, and biochemical parameters. The 96 h LC50 was determined as 189.8 ± 4.5 mg/L, classifying the extract as practically non-toxic, according to OECD guidelines. Thereby, embryos were exposed for 90 h to 75 and 150 mg/L concentrations of the E. japonica leaf extract. While no significant effects were noted at the lowest concentration of 150 mg/L, significant developmental effects were observed, including reduced survival, delayed hatching, underdevelopment of the swim bladder, and retention of the yolk sac. These malformations were accompanied by marked behavioral impairments. Biochemical analysis revealed a concentration-dependent increase in superoxide dismutase (SOD) and catalase (CAT) activity, suggesting the activation of antioxidant defenses, despite no significant change in reactive oxygen species (ROS) levels. This indicates a potential compensatory redox response to a pro-oxidant signal. Additionally, the acetylcholinesterase (AChE) activity was significantly reduced at the highest concentration, which may have contributed to the observed neurobehavioral changes. While AChE inhibition is commonly associated with neurotoxicity, it is also a known therapeutic target in neurodegenerative diseases, suggesting concentration-dependent dual effects. In summary, the E. japonica leaf extract induced concentration-dependent developmental and behavioral effects in zebrafish embryos, while activating antioxidant responses without triggering oxidative damage. These findings highlight the extract’s potential bioactivity and underscore the need for further studies to explore its safety and therapeutic relevance. Full article
(This article belongs to the Special Issue Biological Activities of Traditional Medicinal Plants, 2nd Edition)
20 pages, 6929 KiB  
Article
Protective Effects of Sodium Copper Chlorophyllin and/or Ascorbic Acid Against Barium Chloride-Induced Oxidative Stress in Mouse Brain and Liver
by Salma Benayad, Basma Es-Sai, Yassir Laaziouez, Soufiane Rabbaa, Hicham Wahnou, Habiba Bouchab, Hicham El Attar, Bouchra Benabdelkhalek, Loubna Amahdar, Oualid Abboussi, Raphaël Emmanuel Duval, Riad El Kebbaj and Youness Limami
Molecules 2025, 30(15), 3231; https://doi.org/10.3390/molecules30153231 - 1 Aug 2025
Viewed by 143
Abstract
Barium chloride (BaCl2), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl2-induced oxidative damage in [...] Read more.
Barium chloride (BaCl2), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl2-induced oxidative damage in the liver and brain of mice using a two-phase experimental protocol. Animals received either SCC (40 mg/kg), ASC (160 mg/kg), or their combination for 14 days prior to BaCl2 exposure (150 mg/L in drinking water for 7 days), allowing evaluation of both preventive and therapeutic effects. Toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. Body weight, liver and kidney indices, and biochemical markers (Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), creatinine) remained within physiological ranges, and no anxiogenic or locomotor effects were observed. In the brain, BaCl2 exposure significantly increased SOD (+49%), CAT (+66%), GPx (+24%), and GSH (+26%) compared to controls, reflecting a robust compensatory antioxidant response. Although lipid peroxidation (MDA) showed a non-significant increase, SCC, ASC, and their combination reduced MDA levels by 42%, 37%, and 55%, respectively. These treatments normalized antioxidant enzyme activities and GSH, indicating an effective neuroprotective effect. In contrast, the liver exhibited a different oxidative profile. BaCl2 exposure increased MDA levels by 80% and GSH by 34%, with no activation of SOD, CAT, or GPx. Histological analysis revealed extensive hepatocellular necrosis, vacuolization, and inflammatory infiltration. SCC significantly reduced hepatic MDA by 39% and preserved tissue architecture, while ASC alone or combined with SCC exacerbated inflammation and depleted hepatic GSH by 71% and 78%, respectively, relative to BaCl2-exposed controls. Collectively, these results highlight a differential, organ-specific response to BaCl2-induced oxidative stress and the therapeutic potential of SCC and ASC. SCC emerged as a safer and more effective agent, particularly in hepatic protection, while both antioxidants demonstrated neuroprotective effects when used individually or in combination. Full article
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24 pages, 2572 KiB  
Article
Hair Levels of Lead, Cadmium, Selenium, and Their Associations with Neurotoxicity and Hematological Biomarkers in Children from the Mojana Region, Colombia
by Jenny Palomares-Bolaños, Jesus Olivero-Verbel and Karina Caballero-Gallardo
Molecules 2025, 30(15), 3227; https://doi.org/10.3390/molecules30153227 - 1 Aug 2025
Viewed by 179
Abstract
Heavy metals are a major toxicological concern due to their adverse effects on human health, particularly in children exposed to contaminated areas. This study evaluated biomarkers of exposure in 253 children aged 6 to 12 from Magangue, Achi, and Arjona (Bolivar, Colombia), analyzing [...] Read more.
Heavy metals are a major toxicological concern due to their adverse effects on human health, particularly in children exposed to contaminated areas. This study evaluated biomarkers of exposure in 253 children aged 6 to 12 from Magangue, Achi, and Arjona (Bolivar, Colombia), analyzing their relationship with neurotoxicity and hematological markers. The mean Pb concentrations at the study sites were 1.98 µg/g (Magangue) > 1.51 µg/g (Achi) > 1.24 µg/g (Arjona). A similar pattern was observed for Cd concentrations for Magangue (0.39 µg/g) > Achi (0.36 µg/g) > Arjona (0.14 µg/g). In contrast, Se concentrations followed a different trend for Arjona (0.29 µg/g) > Magangue (0.21 µg/g) > Achi (0.16 µg/g). The proportion of Se/Pb molar ratios > 1 was higher in Arjona (3.8%) than in Magangue (0.9%) and Achi (2.0%). For Se/Cd ratios, values > 1 were also more frequent in Arjona (70.7%), exceeding 20% in the other two locations. Significant differences were found among locations in red and white blood cell parameters and platelet indices. Neurotransmitter-related biomarkers, including serotonin, monoamine oxidase A (MAO-A), and acetylcholinesterase levels, also varied by location. Principal component analysis showed that Pb and Cd had high loadings on the same component as PLT, WBC, and RDW, and while Se loaded together with HGB, PDW, MCHC, MCH, and MCV, suggesting distinct hematological patterns associated with each element. Multiple linear regression analysis demonstrated a statistically significant inverse association between hair Pb levels and serotonin concentrations. Although MAO-A and Cd showed negative β coefficients, these associations were not statistically significant after adjustment. These findings highlight the potential impact of toxic element exposure on key hematological and neurochemical parameters in children, suggesting early biological alterations that may compromise health and neurodevelopment. Full article
(This article belongs to the Section Analytical Chemistry)
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20 pages, 1087 KiB  
Review
Visceral, Neural, and Immunotoxicity of Per- and Polyfluoroalkyl Substances: A Mini Review
by Pietro Martano, Samira Mahdi, Tong Zhou, Yasmin Barazandegan, Rebecca Iha, Hannah Do, Joel Burken, Paul Nam, Qingbo Yang and Ruipu Mu
Toxics 2025, 13(8), 658; https://doi.org/10.3390/toxics13080658 - 31 Jul 2025
Viewed by 236
Abstract
Per- and polyfluoroalkyl substances (PFASs) have gained significant attention due to their widespread distribution in the environment and potential adverse health effects. While ingestion, especially through contaminated drinking water, is considered the primary route of human exposure, recent research suggests that other pathways, [...] Read more.
Per- and polyfluoroalkyl substances (PFASs) have gained significant attention due to their widespread distribution in the environment and potential adverse health effects. While ingestion, especially through contaminated drinking water, is considered the primary route of human exposure, recent research suggests that other pathways, such as inhalation and dermal absorption, also play a significant role. This review provides a concise overview of the toxicological impacts of both legacy and emerging PFASs, such as GenX and perfluorobutane sulfonic acid (PFBS), with a particular focus on their effects on the liver, kidneys, and immune and nervous systems, based on findings from recent in vivo, in vitro, and epidemiological studies. Despite the transition to PFAS alternatives, much of the existing toxicity data focus on a few legacy compounds, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which have been linked to adverse immune outcomes, particularly in children. However, evidence for carcinogenic risk remains limited to populations with extremely high exposure levels, and data on neurodevelopmental effects remain underexplored. While epidemiological and experimental animal studies supported these findings, significant knowledge gaps persist, especially regarding emerging PFASs. Therefore, this review examines the visceral, neural, and immunotoxicity data for emerging PFASs and mixtures from recent studies. Given the known risks from well-studied PFASs, a precautionary principle should be adopted to mitigate human health risks posed by this large and diverse group of chemicals. Full article
(This article belongs to the Section Emerging Contaminants)
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16 pages, 4054 KiB  
Article
Uncovering Fibrocapsa japonica (Raphidophyceae) in South America: First Taxonomic and Toxicological Insights from Argentinean Coastal Waters
by Delfina Aguiar Juárez, Inés Sunesen, Ana Flores-Leñero, Luis Norambuena, Bernd Krock, Gonzalo Fuenzalida and Jorge I. Mardones
Toxins 2025, 17(8), 386; https://doi.org/10.3390/toxins17080386 - 31 Jul 2025
Viewed by 208
Abstract
Fibrocapsa japonica (Raphidophyceae) is a cosmopolitan species frequently associated with harmful algal blooms (HABs) and fish mortality events, representing a potential threat to aquaculture and coastal ecosystems. This study provides the first comprehensive morphological, phylogenetic, pigmentary, and toxicological characterization of F. japonica strains [...] Read more.
Fibrocapsa japonica (Raphidophyceae) is a cosmopolitan species frequently associated with harmful algal blooms (HABs) and fish mortality events, representing a potential threat to aquaculture and coastal ecosystems. This study provides the first comprehensive morphological, phylogenetic, pigmentary, and toxicological characterization of F. japonica strains isolated from Argentina. Light and transmission electron microscopy confirmed key diagnostic features of the species, including anterior flagella and the conspicuous group of mucocyst in the posterior region. Phylogenetic analysis based on the LSU rDNA D1–D2 region revealed monophyletic relationships with strains from geographically distant regions. Pigment analysis by HPLC identified chlorophyll-a (62.3 pg cell−1) and fucoxanthin (38.4 pg cell−1) as the main dominant pigments. Cytotoxicity assays using RTgill-W1 cells exposed for 2 h to culture supernatants and intracellular extracts showed strain-specific effects. The most toxic strain (LPCc049) reduced gill cell viability down to 53% in the supernatant exposure, while LC50 values ranged from 1.6 × 104 to 4.7 × 105 cells mL−1, depending directly on the strain and treatment type. No brevetoxins (PbTx-1, -2, -3, -6, -7, -8, -9, -10, BTX-B1 and BTX-B2) were detected by LC–MS/MS, suggesting that the cytotoxicity may be linked to the production of reactive oxygen species (ROS), polyunsaturated fatty acids (PUFAs), or hemolytic compounds, as previously hypothesized in the literature. These findings offer novel insights into the toxic potential of F. japonica in South America and underscore the need for further research to elucidate the mechanisms underlying its ichthyotoxic effect. Full article
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24 pages, 1117 KiB  
Article
Comparative Analysis of Pesticide Residues in Hive Products from Rapeseed (Brassica napus subsp. napus) and Sunflower (Helianthus annuus) Crops Under Varying Agricultural Practices in Romania During the 2020–2021 Beekeeping Seasons
by Dan Bodescu, Viorel Fătu, Agripina Şapcaliu, Elena Luiza Bădic, Roxana Zaharia, Dana Tăpăloagă, Alexandru-Dragoș Robu and Radu-Adrian Moraru
Agriculture 2025, 15(15), 1648; https://doi.org/10.3390/agriculture15151648 - 31 Jul 2025
Viewed by 202
Abstract
Over the past years, increasing attention has been drawn to the adverse effects of agricultural pesticide use on pollinators, with honeybees being especially vulnerable. The aim of this study was to evaluate the levels of residues detectable and/or quantifiable of neonicotinoid pesticides and [...] Read more.
Over the past years, increasing attention has been drawn to the adverse effects of agricultural pesticide use on pollinators, with honeybees being especially vulnerable. The aim of this study was to evaluate the levels of residues detectable and/or quantifiable of neonicotinoid pesticides and other pesticides in biological materials (bees, bee brood, etc.) and beehive products (honey, pollen, etc.) applied as seed dressings in rapeseed and sunflower plants in two growing seasons (2020–2021) in fields located in three agro-climatic regions in Romania. The study involved the comparative sampling of hive products (honey, pollen, adult bees, and brood) from experimental and control apiaries, followed by pesticide residue analysis in an accredited laboratory (Primoris) using validated chromatographic techniques (LC-MS/MS and GC-MS). Toxicological analyses of 96 samples, including bees, bee brood, honey, and pollen, confirmed the presence of residues in 46 samples, including 10 bee samples, 10 bee brood samples, 18 honey samples, and 8 pollen bread samples. The mean pesticide residue concentrations detected in hive products were 0.032 mg/kg in honey, 0.061 mg/kg in pollen, 0.167 mg/kg in bees, and 0.371 mg/kg in bee brood. The results highlight the exposure of honeybee colonies to multiple sources of pesticide residue contamination, under conditions where legal recommendations for the controlled application of agricultural treatments are not followed. The study provides relevant evidence for strengthening the risk assessment framework and underscores the need for adopting stricter monitoring and regulatory measures to ensure the protection of honeybee colony health. Full article
(This article belongs to the Section Agricultural Product Quality and Safety)
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18 pages, 7265 KiB  
Case Report
New Neonatal and Prenatal Approach to Home Therapy with Amoxicillin, Rifaximin, and Anti-Inflammatory Drugs for Pregnant Women with COVID-19 Infections—Monitoring of Fetal Growth as a Prognostic Factor: A Triple Case Series (N.A.T.H.A.N.)
by Carlo Brogna, Grazia Castellucci, Elrashdy M. Redwan, Alberto Rubio-Casillas, Luigi Montano, Gianluca Ciammetti, Marino Giuliano, Valentina Viduto, Mark Fabrowski, Gennaro Lettieri, Carmela Marinaro and Marina Piscopo
Biomedicines 2025, 13(8), 1858; https://doi.org/10.3390/biomedicines13081858 - 30 Jul 2025
Viewed by 415
Abstract
Background: Since the COVID-19 pandemic, managing acute infections in symptomatic individuals, regardless of vaccination status, has been widely debated and extensively studied. Even more concerning, however, is the impact of COVID-19 on pregnant women—especially its effects on fetuses and newborns. Several studies have [...] Read more.
Background: Since the COVID-19 pandemic, managing acute infections in symptomatic individuals, regardless of vaccination status, has been widely debated and extensively studied. Even more concerning, however, is the impact of COVID-19 on pregnant women—especially its effects on fetuses and newborns. Several studies have documented complications in both expectant mothers and their infants following infection. Methods: In our previous works, we provided scientific evidence of the bacteriophage behavior of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). This demonstrated that a well-defined combination of two antibiotics, amoxicillin and rifaximin, is associated with the same statistics for subjects affected by severe cases of SARS-CoV-2, regardless of vaccination status. We considered the few cases in the literature regarding the management of pregnancies infected with SARS-CoV-2, as well as previous data published in our works. In this brief case series, we present two pregnancies from the same unvaccinated mother—one prior to the COVID-19 pandemic and the other during the spread of the Omicron variant—as well as one pregnancy from a mother vaccinated against COVID-19. We describe the management of acute maternal infection using a previously published protocol that addresses the bacteriophage and toxicological mechanisms associated with SARS-CoV-2. Results: The three pregnancies are compared based on fetal growth and ultrasound findings. This report highlights that, even in unvaccinated mothers, timely and well-guided management of symptomatic COVID-19 can result in positive outcomes. In all cases, intrauterine growth remained within excellent percentiles, and the births resulted in optimal APGAR scores. Conclusions: This demonstrates that a careful and strategic approach, guided by ultrasound controls, can support healthy pregnancies during SARS-CoV-2 infection, regardless of vaccination status. Full article
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37 pages, 497 KiB  
Review
Oxidative Stress and Neurotoxicity Biomarkers in Fish Toxicology
by Grzegorz Formicki, Zofia Goc, Bartosz Bojarski and Małgorzata Witeska
Antioxidants 2025, 14(8), 939; https://doi.org/10.3390/antiox14080939 (registering DOI) - 30 Jul 2025
Viewed by 171
Abstract
Exposure to xenobiotics causes pathophysiological changes in fish, including oxidative stress and neurotoxicity. Here, we describe the biochemical mechanisms underlying oxidative stress (i.e., redox imbalance) and the biochemical markers commonly used to assess its level. Neurotoxicity biomarkers used in fish include behavioral, histological, [...] Read more.
Exposure to xenobiotics causes pathophysiological changes in fish, including oxidative stress and neurotoxicity. Here, we describe the biochemical mechanisms underlying oxidative stress (i.e., redox imbalance) and the biochemical markers commonly used to assess its level. Neurotoxicity biomarkers used in fish include behavioral, histological, molecular, neurotransmitter-related, and enzymatic parameters, among which acetylcholinesterase (AChE) activity is the most commonly measured. We therefore also review the changes in AChE activity in fish exposed to common xenobiotics. In most cases, AChE activity decreased in a concentration- and time-dependent manner, although some studies reported no change or even an increase. We emphasize the relevance of all the parameters discussed in the context of fish toxicology studies. Full article
(This article belongs to the Special Issue Reactive Oxygen Species Signalling and Oxidative Stress in Fish)
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