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Search Results (550)

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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 (registering DOI) - 1 Aug 2025
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 (registering DOI) - 31 Jul 2025
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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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
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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19 pages, 1599 KiB  
Article
Nanopolystyrene (nanoPS) and Sodium Azide (NaN3) Toxicity in Danio rerio: Behavioural and Morphological Evaluation
by Wanda Komorowska, Łukasz Kurach and Agnieszka Dąbrowska
Microplastics 2025, 4(3), 45; https://doi.org/10.3390/microplastics4030045 - 29 Jul 2025
Viewed by 188
Abstract
Nano- (NPs) and microplastics (MPs) are ubiquitous and raising concerns about their toxicity. A popular model for studying acute toxicity is Danio rerio. This study investigated the acute toxicity in FET test of polystyrene nanoparticles (500 nm, nanoPS) at different concentrations (0.01, [...] Read more.
Nano- (NPs) and microplastics (MPs) are ubiquitous and raising concerns about their toxicity. A popular model for studying acute toxicity is Danio rerio. This study investigated the acute toxicity in FET test of polystyrene nanoparticles (500 nm, nanoPS) at different concentrations (0.01, 0.1, and 0.2 mg/mL), with different surface groups (non-modified, amine, carboxyl) and discuss the toxicological contribution of commercially added compounds. Different behavioural tests were used to investigate the neurotoxicity of nanoPS and sodium azide: coiling assay test, light–dark preference test, and colour preference test. Sodium azide and other preservatives are often present in commercially available NP and MP solutions frequently used in microplastic toxicity tests, but their effects on the results remain largely unknown. In the FET test, nanoPS did not increase mortality or affect the heart rate or body length. A higher hatching rate was observed at 48 hpf. Although nanoPS showed no acute toxicity, behavioural tests revealed subtle neurotoxic effects (changes in colour preference), suggesting a potential impact on neurological function. Additionally, sodium azide exhibited toxicity, indicating that additives may confound toxicity assessments. This highlights the need for careful consideration of preservatives in nanoparticle research to avoid misleading conclusions. Full article
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28 pages, 1775 KiB  
Review
Forensic Narcotics Drug Analysis: State-of-the-Art Developments and Future Trends
by Petar Ristivojević, Božidar Otašević, Petar Todorović and Nataša Radosavljević-Stevanović
Processes 2025, 13(8), 2371; https://doi.org/10.3390/pr13082371 - 25 Jul 2025
Viewed by 370
Abstract
Narcotics trafficking is a fundamental part of organized crime, posing significant and evolving challenges for forensic investigations. Addressing these challenges requires rapid, precise, and scientifically validated analytical methods for reliable identification of illicit substances. Over the past five years, forensic drug testing has [...] Read more.
Narcotics trafficking is a fundamental part of organized crime, posing significant and evolving challenges for forensic investigations. Addressing these challenges requires rapid, precise, and scientifically validated analytical methods for reliable identification of illicit substances. Over the past five years, forensic drug testing has advanced considerably, improving detection of traditional drugs—such as tetrahydrocannabinol, cocaine, heroin, amphetamine-type stimulants, and lysergic acid diethylamide—as well as emerging new psychoactive substances (NPS), including synthetic cannabinoids (e.g., 5F-MDMB-PICA), cathinones (e.g., α-PVP), potent opioids (e.g., carfentanil), designer psychedelics (e.g., 25I-NBOMe), benzodiazepines (e.g., flualprazolam), and dissociatives (e.g., 3-HO-PCP). Current technologies include colorimetric assays, ambient ionization mass spectrometry, and chromatographic methods coupled with various detectors, all enhancing accuracy and precision. Vibrational spectroscopy techniques, like Raman and Fourier transform infrared spectroscopy, have become essential for non-destructive identification. Additionally, new sensors with disposable electrodes and miniaturized transducers allow ultrasensitive on-site detection of drugs and metabolites. Advanced chemometric algorithms extract maximum information from complex data, enabling faster and more reliable identifications. An important emerging trend is the adoption of green analytical methods—including direct analysis, solvent-free extraction, miniaturized instruments, and eco-friendly chromatographic processes—that reduce environmental impact without sacrificing performance. This review provides a comprehensive overview of innovations over the last five years in forensic drug analysis based on the ScienceDirect database and highlights technological trends shaping the future of forensic toxicology. Full article
(This article belongs to the Special Issue Feature Review Papers in Section “Pharmaceutical Processes”)
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21 pages, 1784 KiB  
Article
Toxic Threats from the Fern Pteridium aquilinum: A Multidisciplinary Case Study in Northern Spain
by L. María Sierra, Isabel Feito, Mª Lucía Rodríguez, Ana Velázquez, Alejandra Cué, Jaime San-Juan-Guardado, Marta Martín, Darío López, Alexis E. Peña, Elena Canga, Guillermo Ramos, Juan Majada, José Manuel Alvarez and Helena Fernández
Int. J. Mol. Sci. 2025, 26(15), 7157; https://doi.org/10.3390/ijms26157157 - 24 Jul 2025
Viewed by 175
Abstract
Pteridium aquilinum (bracken fern) poses a global threat to biodiversity and to the health of both animals and humans due to its toxic metabolites and aggressive ecological expansion. In northern Spain, particularly in regions of intensive livestock farming, these risks may be exacerbated, [...] Read more.
Pteridium aquilinum (bracken fern) poses a global threat to biodiversity and to the health of both animals and humans due to its toxic metabolites and aggressive ecological expansion. In northern Spain, particularly in regions of intensive livestock farming, these risks may be exacerbated, calling for urgent assessment and monitoring strategies. In this study, we implemented a multidisciplinary approach to evaluate the toxicological and ecological relevance of P. aquilinum through four key actions: (a) quantification of pterosins A and B in young fronds (croziers) using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS); (b) analysis of in vivo genotoxicity of aqueous extracts using Drosophila melanogaster as a model organism; (c) a large-scale survey of local livestock farmers to assess awareness and perceived impact of bracken; and (d) the development and field application of a drone-based mapping tool to assess the spatial distribution of the species at the regional level. Our results confirm the consistent presence of pterosins A and B in croziers, with concentrations ranging from 0.17 to 2.20 mg/g dry weight for PtrB and 13.39 to 257 µg/g for PtrA. Both metabolite concentrations and genotoxicity levels were found to correlate with latitude and, importantly, with each other. All tested samples exhibited genotoxic activity, with notable differences among them. The farmer survey (n = 212) revealed that only 50% of respondents were aware of the toxic risks posed by bracken, indicating a need for targeted outreach. The drone-assisted mapping approach proved to be a promising tool for identifying bracken-dominated areas and provides a scalable foundation for future ecological monitoring and land management strategies. Altogether, our findings emphasize that P. aquilinum is not merely a local concern but a globally relevant toxic species whose monitoring and control demand coordinated scientific and policy-based efforts. Full article
(This article belongs to the Special Issue The Transcendental World of Plant Toxic Compounds)
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15 pages, 302 KiB  
Review
Pruritus in Palliative Care: A Narrative Review of Essential Oil-Based Strategies to Alleviate Cutaneous Discomfort
by Sara Diogo Gonçalves
Diseases 2025, 13(8), 232; https://doi.org/10.3390/diseases13080232 - 23 Jul 2025
Viewed by 181
Abstract
Pruritus is a common and distressing symptom in palliative care, often resulting from complex underlying conditions such as cancer, chronic kidney disease, and liver failure. Conventional pharmacological treatments frequently offer limited relief and may produce undesirable side effects in this medically fragile population. [...] Read more.
Pruritus is a common and distressing symptom in palliative care, often resulting from complex underlying conditions such as cancer, chronic kidney disease, and liver failure. Conventional pharmacological treatments frequently offer limited relief and may produce undesirable side effects in this medically fragile population. Despite the high prevalence and impact of pruritus in palliative care, there is a lack of consolidated evidence on integrative non-pharmacological approaches. This narrative review explores the potential role of essential oils as a complementary approach to managing pruritus in palliative settings. A review of the literature was conducted to examine the mechanisms of action, safety considerations, and clinical outcomes associated with the use of essential oils, with a particular focus on their anti-inflammatory, neuromodulatory, and soothing properties. Evidence suggests that essential oils may provide symptom relief and enhance quality of life when integrated into multidisciplinary care; however, small sample sizes, heterogeneity, and methodological weaknesses often limit the findings of these studies. Furthermore, the long-term safety and antigenotoxic potential of essential oils remain underexplored. This narrative review concludes that while essential oils appear promising as adjunct therapies for pruritus, further rigorous research, particularly well-designed clinical trials and toxicological assessments, is needed to support their safe and effective use in palliative care. Full article
25 pages, 400 KiB  
Review
Microplastic Uptake in Vegetables: Sources, Mechanisms, Transport and Food Safety
by Zorana Srećkov, Zorica Mrkonjić, Mirjana Bojović, Olivera Nikolić, Danka Radić and Vesna Vasić
Toxics 2025, 13(8), 609; https://doi.org/10.3390/toxics13080609 - 22 Jul 2025
Viewed by 372
Abstract
Although microplastic pollution has been recognized as one of the major environmental challenges of the 21st century, its toxicological impact on crops, especially vegetables, has attracted limited scientific attention until recently. Vegetables represent a key component of the human diet, making any potential [...] Read more.
Although microplastic pollution has been recognized as one of the major environmental challenges of the 21st century, its toxicological impact on crops, especially vegetables, has attracted limited scientific attention until recently. Vegetables represent a key component of the human diet, making any potential contamination of great importance for food safety. In recent years, an increasing number of studies have been conducted to investigate the interactions between microplastics and vegetable crops. This review aims to synthesize the current knowledge on the sources of microplastics in agroecosystems, the mechanisms of uptake and translocation in plants, and the physiological and biochemical responses induced by micro- and nanoplastics. This work aims to improve the scientific basis for assessing the risk of microplastic contamination by identifying gaps in current understanding and suggesting future research directions. Full article
(This article belongs to the Section Emerging Contaminants)
17 pages, 985 KiB  
Review
Advances in Forensic Entomotoxicology for Decomposed Corpses: A Review
by Sen Hou, Zengjia Liu, Jiali Su, Zeyu Yang, Zhongjiang Wang, Xinyi Yao, Zhou Lyu, Yang Xia, Shuguang Zhang, Wen Cui, Yequan Wang and Lipin Ren
Insects 2025, 16(7), 744; https://doi.org/10.3390/insects16070744 - 21 Jul 2025
Viewed by 347
Abstract
Forensic entomotoxicology is a subdiscipline that utilizes necrophagous insects as bioindicators for detecting drugs and toxicants in decomposed remains, particularly in cases where conventional biological matrices are no longer available. Toxic substances can profoundly alter insect development, physiology, and community succession, potentially impacting [...] Read more.
Forensic entomotoxicology is a subdiscipline that utilizes necrophagous insects as bioindicators for detecting drugs and toxicants in decomposed remains, particularly in cases where conventional biological matrices are no longer available. Toxic substances can profoundly alter insect development, physiology, and community succession, potentially impacting the accuracy of postmortem interval (PMI) estimation. This review systematically summarizes the effects of various xenobiotics, including pesticides, illicit drugs, sedatives, heavy metals, and antibiotics on larval growth, physiological traits, and gut microbial composition in forensically relevant flies. However, most studies to date have relied primarily on phenotypic observations, with limited insight into underlying molecular mechanisms. Significant interspecies and dose-dependent variability also exists in the absorption, metabolism, and physiological responses to xenobiotics. We highlight recent advances in multi-omics technologies that facilitate the identification of molecular biomarkers associated with xenobiotic exposure, particularly within the insect detoxification system. Key components such as cytochrome P450 monooxygenases (P450s), glutathione S-transferases (GSTs), and ATP-binding cassette (ABC) transporters play essential roles in xenobiotic metabolism and insecticide resistance. Additionally, the insect fat body serves as a central hub for detoxification, hormonal regulation, and energy metabolism. It integrates signals related to xenobiotic exposure and modulates larval development, making it a promising model for future mechanistic studies in insect toxicology. Altogether, this review offers a comprehensive and reliable framework for understanding the complex interactions between toxic substance exposure, insect ecology, and decomposition in forensic investigations. Full article
(This article belongs to the Section Medical and Livestock Entomology)
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16 pages, 1624 KiB  
Article
Neurobehavioral and Oxidative Stress Effects of SiO2 Nanoparticles in Zebrafish and the Protective Role of N-Acetylcysteine
by Viorica Rarinca, Irina-Luciana Gurzu, Mircea Nicusor Nicoara, Alin Ciobica, Malina Visternicu, Catalina Ionescu, Ioana Miruna Balmus, Gabriel-Ionut Plavan, Elena Todirascu-Ciornea and Bogdan Gurzu
Biomedicines 2025, 13(7), 1762; https://doi.org/10.3390/biomedicines13071762 - 18 Jul 2025
Viewed by 379
Abstract
Background/Objectives: Silicon dioxide nanoparticles (SiO2NPs) do not exist in isolation in the environment but can interact with other substances, thus influencing their toxic effects on aquatic organisms. We assessed the combined impact of SiO2NPs and N-acetylcysteine (NAC), an antioxidant [...] Read more.
Background/Objectives: Silicon dioxide nanoparticles (SiO2NPs) do not exist in isolation in the environment but can interact with other substances, thus influencing their toxic effects on aquatic organisms. We assessed the combined impact of SiO2NPs and N-acetylcysteine (NAC), an antioxidant with the potential to counteract nanoparticle-induced oxidative stress (OS). Methods: Behavioral assessments, including the social interaction test and color preference test, were performed to evaluate neurobehavioral changes. OS biomarkers, including malondialdehyde (MDA) levels for lipid peroxidation and the activity of key antioxidant enzymes such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), were assessed to evaluate the extent of cellular damage. Results: The results indicate that prolonged exposure to SiO2NPs induces significant behavioral disruptions, including reduced exploratory behavior and increased anxiety-like responses. Furthermore, biochemical analysis revealed increased OS, suggesting nanoparticle-induced cellular toxicity. NAC co-treatment partially reversed these effects, particularly improving locomotor outcomes and antioxidant response, but was less effective on social behavior. Conclusions: These findings highlight the ecological and health risks posed by SiO2NPs and point toward the need for further toxicological studies on their long-term biological effects. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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18 pages, 1268 KiB  
Review
Perspectives on the Presence of Environmentally Persistent Free Radicals (EPFRs) in Ambient Particulate Matters and Their Potential Implications for Health Risk
by Senlin Lu, Jiakuan Lu, Xudong Wang, Kai Xiao, Jingying Niuhe, Xinchun Liu and Shinichi Yonemochi
Atmosphere 2025, 16(7), 876; https://doi.org/10.3390/atmos16070876 - 17 Jul 2025
Viewed by 185
Abstract
Environmental persistent free radicals (EPFRs) represent a class of long-lived, redox-active species with half lives spanning minutes to months. Emerging as critical environmental pollutants, EPFRs pose significant risks due to their persistence, potential for bioaccumulation, and adverse effects on ecosystems and human health. [...] Read more.
Environmental persistent free radicals (EPFRs) represent a class of long-lived, redox-active species with half lives spanning minutes to months. Emerging as critical environmental pollutants, EPFRs pose significant risks due to their persistence, potential for bioaccumulation, and adverse effects on ecosystems and human health. This review critically synthesizes recent advancements in understanding EPFR formation mechanisms, analytical detection methodologies, environmental distribution patterns, and toxicological impacts. While progress has been made in characterization techniques, challenges persist—particularly in overcoming limitations of electron paramagnetic resonance (EPR) spectroscopy and spin-trapping methods in complex environmental matrices. Key knowledge gaps remain, including molecular-level dynamics of EPFR formation, long-term environmental fate under varying geochemical conditions, and quantitative relationships between chronic EPFR exposure and health outcomes. Future research priorities could focus on: (1) atomic-scale mechanistic investigations using advanced computational modeling to resolve formation pathways; (2) development of next-generation detection tools to improve sensitivity and spatial resolution; and (3) integration of EPFR data into region-specific air-quality indices to enhance risk assessment and inform mitigation strategies. Addressing these gaps will advance our capacity to mitigate EPFR persistence and safeguard environmental and public health. Full article
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28 pages, 5314 KiB  
Article
Environmental Cyanide Pollution from Artisanal Gold Mining in Burkina Faso: Human Exposure Risk Analysis Based on a Conceptual Site Model
by Edmond N’Bagassi Kohio, Seyram Kossi Sossou, Hela Karoui and Hamma Yacouba
Int. J. Environ. Res. Public Health 2025, 22(7), 1125; https://doi.org/10.3390/ijerph22071125 - 16 Jul 2025
Viewed by 395
Abstract
Artisanal and small-scale gold mining (ASGM) in Burkina Faso increasingly relies on cyanide, intensifying concerns about environmental contamination and human exposure. This study assessed free cyanide levels in water and soil across three ASGM sites—Zougnazagmiline, Guido, and Galgouli. Water samples (surface and groundwater) [...] Read more.
Artisanal and small-scale gold mining (ASGM) in Burkina Faso increasingly relies on cyanide, intensifying concerns about environmental contamination and human exposure. This study assessed free cyanide levels in water and soil across three ASGM sites—Zougnazagmiline, Guido, and Galgouli. Water samples (surface and groundwater) and topsoil (0–20 cm) were analyzed using the pyridine–pyrazolone method. Data were statistically and spatially processed using SPSS version 29.0 and the Google Earth Engine in conjunction with QGIS version 3.34, respectively. A site conceptual model (SCM) was also developed, based on the literature review, field observations, and validation by multidisciplinary experts in public health, toxicology, ecotoxicology, environmental engineering, and the mining sector, through a semi-structured survey. The results showed that 9.26% of the water samples exceeded the WHO guideline (0.07 mg/L), with peaks of 1.084 mg/L in Guido and 2.42 mg/L in Galgouli. At Zougnazagmiline, the water type differences were significant (F = 64.13; p < 0.001), unlike the other sites. In the soil, 29.36% of the samples exceeded 0.5 mg/kg, with concentrations reaching 9.79 mg/kg in Galgouli. A spatial analysis revealed pollution concentrated near the mining areas but spreading to residential and agricultural zones. The validated SCM integrates pollution sources, transport mechanisms, exposure routes, and vulnerable populations, offering a structured tool for environmental monitoring and health risk assessment in cyanide-impacted mining regions. Full article
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23 pages, 1877 KiB  
Article
Synthesis and Cytotoxicity Evaluation of Denitroaristolochic Acids: Structural Insights and Mechanistic Implications in Nephrotoxicity
by Jianfei Gao, Mengtong Zhao, Jianhua Su, Yi Gao, Xiaofeng Zhang, Yongzhao Ding, Xiaoping Liu, Yang Luan and Chun Hu
Biomolecules 2025, 15(7), 1014; https://doi.org/10.3390/biom15071014 - 14 Jul 2025
Viewed by 277
Abstract
The efficient synthetic routes and evaluates cytotoxic profiles of denitroaristolochic acids II–V (DAA-II–V) were demonstrated in this study. Based on retrosynthetic analysis, a modular synthetic strategy was developed through Suzuki–Miyaura coupling, Wittig reaction, and bismuth triflate-catalyzed intramolecular Friedel–Crafts cyclization to efficiently construct the [...] Read more.
The efficient synthetic routes and evaluates cytotoxic profiles of denitroaristolochic acids II–V (DAA-II–V) were demonstrated in this study. Based on retrosynthetic analysis, a modular synthetic strategy was developed through Suzuki–Miyaura coupling, Wittig reaction, and bismuth triflate-catalyzed intramolecular Friedel–Crafts cyclization to efficiently construct the phenanthrene core. Process optimization significantly improved yields: aryl bromide intermediate A reached 50.8% yield via bromination refinement, while arylboronic ester intermediate B overcame selectivity limitations. Combining Darzens condensation with Wittig reaction enhanced throughput, achieving 88.4% yield in the key cyclization. Structures were confirmed by NMR and mass spectra. CCK-8 cytotoxicity assays in human renal proximal tubular epithelial cells revealed distinct toxicological profiles: DAA-III and DAA-IV exhibited IC50 values of 371 μM and 515 μM, respectively, significantly higher than the nitro-containing prototype AA-I (270 μM), indicating that the absence of nitro group attenuates but does not eliminate toxicity, potentially via altered metabolic activation. DAA-II and DAA-V showed no detectable cytotoxicity within assay limits, suggesting reduced toxicological impact. Structure–activity analysis exhibited that the nitro group is not essential for cytotoxicity, with methoxy substituents exerting limited influence on potency. This challenges the conventional DNA adduct-dependent toxicity paradigm, implying alternative mechanisms like oxidative stress or mitochondrial dysfunction may mediate damage in denitro derivatives. These systematic findings provide new perspectives for AA analog research and a foundation for the rational use and safety assessment of Aristolochiaceae plants. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
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22 pages, 1875 KiB  
Article
Biochemical Identification and Clinical Description of Medetomidine Exposure in People Who Use Fentanyl in Philadelphia, PA
by Phil Durney, Jennifer L. Kahoud, TaReva Warrick-Stone, Maeve Montesi, Meg Carter, Sabrina Butt, Alberto Martinez Mencia, Louisa Omoregie, Monali Shah, Mariah Bloomfield, Nicholas Tomasko, Rebecca Jaffe, Allison Herens, Warren R. Korn, Karen Alexander, Douglas Stickle, Dennis Goodstein, Lara Carson Weinstein and Kory S. London
Int. J. Mol. Sci. 2025, 26(14), 6715; https://doi.org/10.3390/ijms26146715 - 13 Jul 2025
Viewed by 418
Abstract
Medetomidine, a veterinary α2-adrenergic agonist, has recently emerged as an adulterant in the non-medical opioid supply, yet human exposure has remained poorly characterized. We conducted a pragmatic retrospective cohort analysis utilizing chart review and liquid chromatography–tandem mass spectrometry (LC-MS/MS) toxicology testing on available [...] Read more.
Medetomidine, a veterinary α2-adrenergic agonist, has recently emerged as an adulterant in the non-medical opioid supply, yet human exposure has remained poorly characterized. We conducted a pragmatic retrospective cohort analysis utilizing chart review and liquid chromatography–tandem mass spectrometry (LC-MS/MS) toxicology testing on available urine samples from patients presenting to two hospitals in Philadelphia, PA, who fit two clinical phenotypes, intoxication or withdrawal. Samples also underwent glucuronidase pre-treatment to assess impact on the yield of medetomidine and xylazine metabolite detection. Testing identified universal exposure to medetomidine (58/58 samples) via the 3-hydroxy-medetomidine (3-OH-M) metabolite, post glucuronidase treatment and variable xylazine exposure (40/58 samples). Importantly, 32% of medetomidine exposures would have been missed without enzymatic pre-treatment. Patients exhibited two distinct clinical phenotypes: intoxication, characterized primarily by sedation; bradycardia; and often hypotension, and withdrawal, presenting with life-threatening tachycardia; hypertension and often encephalopathy. Notably, clinical phenotype correlated with urinary concentrations of 3-OH-M but not xylazine. These findings underscore the critical need for heightened clinical awareness and need for contemporaneous toxicologic screening mechanisms for medetomidine exposure, emphasizing its distinct clinical presentations and the potential public health implications posed by its widespread adulteration in illicit opioids. Full article
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24 pages, 6814 KiB  
Review
Modulatory Effects of Urtica dioica on Neurodegenerative Diseases: Unveiling the Latest Findings and Applications Related to Neuroinflammation, Oxidative Stress, and Cognitive Dysfunction
by Ahlem Chira and Stefano Lorenzetti
Antioxidants 2025, 14(7), 854; https://doi.org/10.3390/antiox14070854 - 12 Jul 2025
Viewed by 1117
Abstract
Over the past decade, Urtica dioica L. (U. dioica) has gained prominence in biomedical research, particularly for its potential therapeutic applications in neurodegenerative diseases. This comprehensive review explores its botanical characteristics, toxicological considerations, and extensive traditional medicinal uses. Emphasizing the roles [...] Read more.
Over the past decade, Urtica dioica L. (U. dioica) has gained prominence in biomedical research, particularly for its potential therapeutic applications in neurodegenerative diseases. This comprehensive review explores its botanical characteristics, toxicological considerations, and extensive traditional medicinal uses. Emphasizing the roles of phytochemical constituents such as flavonoids and overall polyphenolic compounds, this review examines their impact on mitigating critical pathways, such as neuroinflammation, oxidative stress, and mitochondrial dysfunction—all of which are implicated in Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and Multiple Sclerosis (MS)—and, overall, in neurodegenerative processes in both humans and animal models. Notably, some phytochemicals are known to modulate crucial pathways for neuronal plasticity, learning, and memory, thereby enhancing cognitive functions. Hence, the potential of U. dioica-based therapies to improve cognitive function and pave the way for future therapeutic developments in neuroprotection is underscored. Full article
(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Components of the Diet)
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