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Keywords = animal toxicological safety

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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 186
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, 384 KiB  
Review
Potential Metal Contamination in Foods of Animal Origin—Food Safety Aspects
by József Lehel, Dániel Pleva, Attila László Nagy, Miklós Süth and Tibor Kocsner
Appl. Sci. 2025, 15(15), 8468; https://doi.org/10.3390/app15158468 - 30 Jul 2025
Viewed by 196
Abstract
This literature review provides an overview of the food safety and toxicological characteristics of various heavy metals and metalloids and the public health significance of their occurrence in food. Metals also occur as natural components of the environment, but they can enter food [...] Read more.
This literature review provides an overview of the food safety and toxicological characteristics of various heavy metals and metalloids and the public health significance of their occurrence in food. Metals also occur as natural components of the environment, but they can enter food of animal origin and the human body primarily due to anthropogenic (industrial, agricultural, transport-related) activities. The persistent heavy metals (e.g., Hg, Pb, Cd) found in the environment are not biodegradable, can accumulate, and can enter the bodies of higher animals and subsequently, humans, where they are metabolized into various compounds with differing toxicity. Thus, due to their environmental contamination, they can accumulate in living organisms and their presence in the food chain is of great concern for human health. Regulations of the European Community in force lay down maximum levels for a limited number of metals, and the types of regulated foodstuffs of animal origin are also narrower than in the past, e.g., wild game animals and eggs are not included. The regulation of game meat (including offal) deserves consideration, given that it is in close interaction with the environmental condition of a given area and serves as indicator of it. Full article
20 pages, 1243 KiB  
Article
Comparison of Capillary Electrophoresis and HPLC-Based Methods in the Monitoring of Moniliformin in Maize
by Sara Astolfi, Francesca Buiarelli, Francesca Debegnach, Barbara De Santis, Patrizia Di Filippo, Donatella Pomata, Carmela Riccardi and Giulia Simonetti
Foods 2025, 14(15), 2623; https://doi.org/10.3390/foods14152623 - 26 Jul 2025
Viewed by 188
Abstract
Over the past few decades, scientific interest in mycotoxins—fungal metabolites that pose serious concern to food safety, crop health, and both human and animal health—has increased. While major mycotoxins such as aflatoxins, ochratoxins, deoxynivalenol, fumonisins, zearalenone, citrinin, patulin, and ergot alkaloids are well [...] Read more.
Over the past few decades, scientific interest in mycotoxins—fungal metabolites that pose serious concern to food safety, crop health, and both human and animal health—has increased. While major mycotoxins such as aflatoxins, ochratoxins, deoxynivalenol, fumonisins, zearalenone, citrinin, patulin, and ergot alkaloids are well studied, emerging mycotoxins remain underexplored and insufficiently investigated. Among these, moniliformin (MON) is frequently detected in maize-based food and feed; however, the absence of regulatory limits and standardized detection methods limits effective monitoring and comprehensive risk assessment. The European Food Safety Authority highlights insufficient occurrence and toxicological data as challenges to regulatory development. This study compares three analytical methods—CE-DAD, HPLC-DAD, and HPLC-MS/MS—for moniliformin detection and quantification in maize, evaluating linear range, correlation coefficients, detection and quantification limits, accuracy, and precision. Results show that CE-DAD and HPLC-MS/MS provide reliable and comparable sensitivity and selectivity, while HPLC-DAD is less sensitive. Application to real samples enabled deterministic dietary exposure estimation based on consumption, supporting preliminary risk characterization. This research provides a critical comparison that supports the advancement of improved monitoring and risk assessment frameworks, representing a key step toward innovating the detection of under-monitored mycotoxins and laying the groundwork for future regulatory and preventive measures targeting MON. Full article
(This article belongs to the Special Issue Recent Advances in the Detection of Food Contaminants and Pollutants)
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16 pages, 3973 KiB  
Article
Toxicological Risk Assessment and Source Identification of Groundwater Pollution: A Case of Sheep Herd Damage in a Pastoral Area
by Wei Wang, Honger Cheng, Yuewei Yang, Jianjun Su, Jialu Sun, Xiaojing Li and Qian Zhao
Environments 2025, 12(7), 240; https://doi.org/10.3390/environments12070240 - 14 Jul 2025
Viewed by 506
Abstract
Improper emissions from industrial activities pose toxicological risks to groundwater safety. Based on an environmental forensic identification case involving livestock (sheep) damage caused by groundwater pollution in a pastoral area, we comprehensively evaluated groundwater quality risks, toxicological risks, and pollution sources using multivariate [...] Read more.
Improper emissions from industrial activities pose toxicological risks to groundwater safety. Based on an environmental forensic identification case involving livestock (sheep) damage caused by groundwater pollution in a pastoral area, we comprehensively evaluated groundwater quality risks, toxicological risks, and pollution sources using multivariate statistical methods, the Nemerow index method, and a non-carcinogenic health risk model. The potential specific pollutants in the region mainly included calcium, potassium, sodium, magnesium, manganese, fluoride, chloride, sulfate, ammonia nitrogen, total dissolved solids, and nitrate. An evaluation of the groundwater health risk factors showed that fluoride, nitrate, and manganese pose higher health risks (HQ > 1), as fluoride > nitrate > manganese. This suggests that these three pollutants were the primary causes of livestock damage. Identification of pollution sources using multivariate statistical analysis revealed that the main pollutants in the groundwater originate from two rare earth enterprises in the surrounding industrial park, followed by the emissions from animal husbandry. This study provides guidelines into comprehensive regional toxicological risk assessment and source tracing, offering an identification method for similar forensic environmental damage cases. Full article
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22 pages, 3768 KiB  
Article
MWB_Analyzer: An Automated Embedded System for Real-Time Quantitative Analysis of Morphine Withdrawal Behaviors in Rodents
by Moran Zhang, Qianqian Li, Shunhang Li, Binxian Sun, Zhuli Wu, Jinxuan Liu, Xingchao Geng and Fangyi Chen
Toxics 2025, 13(7), 586; https://doi.org/10.3390/toxics13070586 - 14 Jul 2025
Viewed by 434
Abstract
Background/Objectives: Substance use disorders, particularly opioid addiction, continue to pose a major global health and toxicological challenge. Morphine dependence represents a significant problem in both clinical practice and preclinical research, particularly in modeling the pharmacodynamics of withdrawal. Rodent models remain indispensable for investigating [...] Read more.
Background/Objectives: Substance use disorders, particularly opioid addiction, continue to pose a major global health and toxicological challenge. Morphine dependence represents a significant problem in both clinical practice and preclinical research, particularly in modeling the pharmacodynamics of withdrawal. Rodent models remain indispensable for investigating the neurotoxicological effects of chronic opioid exposure and withdrawal. However, conventional behavioral assessments rely on manual observation, limiting objectivity, reproducibility, and scalability—critical constraints in modern drug toxicity evaluation. This study introduces MWB_Analyzer, an automated and high-throughput system designed to quantitatively and objectively assess morphine withdrawal behaviors in rats. The goal is to enhance toxicological assessments of CNS-active substances through robust, scalable behavioral phenotyping. Methods: MWB_Analyzer integrates optimized multi-angle video capture, real-time signal processing, and machine learning-driven behavioral classification. An improved YOLO-based architecture was developed for the accurate detection and categorization of withdrawal-associated behaviors in video frames, while a parallel pipeline processed audio signals. The system incorporates behavior-specific duration thresholds to isolate pharmacologically and toxicologically relevant behavioral events. Experimental animals were assigned to high-dose, low-dose, and control groups. Withdrawal was induced and monitored under standardized toxicological protocols. Results: MWB_Analyzer achieved over 95% reduction in redundant frame processing, markedly improving computational efficiency. It demonstrated high classification accuracy: >94% for video-based behaviors (93% on edge devices) and >92% for audio-based events. The use of behavioral thresholds enabled sensitive differentiation between dosage groups, revealing clear dose–response relationships and supporting its application in neuropharmacological and neurotoxicological profiling. Conclusions: MWB_Analyzer offers a robust, reproducible, and objective platform for the automated evaluation of opioid withdrawal syndromes in rodent models. It enhances throughput, precision, and standardization in addiction research. Importantly, this tool supports toxicological investigations of CNS drug effects, preclinical pharmacokinetic and pharmacodynamic evaluations, drug safety profiling, and regulatory assessment of novel opioid and CNS-active therapeutics. Full article
(This article belongs to the Section Drugs Toxicity)
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24 pages, 792 KiB  
Review
Microplastics-Assisted Campylobacter Persistence, Virulence, and Antimicrobial Resistance in the Food Chain: An Overview
by Irene Ortega-Sanz and Andreja Rajkovic
Foods 2025, 14(14), 2432; https://doi.org/10.3390/foods14142432 - 10 Jul 2025
Viewed by 514
Abstract
Recent studies have detected microplastics (MPs) in seafood and various food products worldwide, including poultry, fish, salt, beverages, fruits, and vegetables. This widespread contamination makes human exposure through consumption unavoidable and raises concerns for food safety and human health. MPs provide physical support [...] Read more.
Recent studies have detected microplastics (MPs) in seafood and various food products worldwide, including poultry, fish, salt, beverages, fruits, and vegetables. This widespread contamination makes human exposure through consumption unavoidable and raises concerns for food safety and human health. MPs provide physical support to microorganisms for biofilm formation, protecting them from extreme conditions and facilitating their persistence in the environment. However, little is known about the impact of MPs in the transmission of foodborne pathogens and subsequent spread of infectious diseases like campylobacteriosis, the most common foodborne illness caused by a bacterium, Campylobacter. This review explores the sources of MP contamination in the food chain and offers a comprehensive overview of MP presence in animals, food products, and beverages. Moreover, we compile the available studies linking MPs and Campylobacter and examine the potential impact of these particles on the transmission of Campylobacter along the food chain with a particular focus on poultry, the main source and reservoir for the pathogen. While the environmental and toxicological effects of MPs are increasingly understood, their influence on the virulence of Campylobacter and the spread of antimicrobial resistance remains underexplored. Further studies are needed to develop standardized methods for isolating and identifying MPs, enabling comprehensive investigations and more effective monitoring and risk mitigation strategies. Full article
(This article belongs to the Section Food Toxicology)
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11 pages, 3387 KiB  
Article
Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging (IDESI-MSI) Reveals Absorption of Triclopyr-Based Herbicide in Plants and Mouse Organs
by Hanzhi Liu, Yunshuo Tian, Ruolun Wei, Yifan Meng and Richard N. Zare
Metabolites 2025, 15(7), 437; https://doi.org/10.3390/metabo15070437 - 30 Jun 2025
Viewed by 369
Abstract
Background: Understanding the absorption and distribution of herbicides in plants and animal tissues is essential for assessing their potential risks to human health. Method: In this study, we employed imprint desorption electrospray ionization mass spectrometry imaging (IDESI-MSI) to visualize in both vegetable and [...] Read more.
Background: Understanding the absorption and distribution of herbicides in plants and animal tissues is essential for assessing their potential risks to human health. Method: In this study, we employed imprint desorption electrospray ionization mass spectrometry imaging (IDESI-MSI) to visualize in both vegetable and animal tissues the absorption of Roundup which is a widely used herbicide. Results: Using IDESI-MSI with a pixel size of 150 µm, we detected the herbicide alongside several endogenous metabolites on oil-absorbing films applied to carrot sections. Time-course experiments revealed progressive herbicide penetration into carrot tissue, with penetration depth increasing linearly over time at a rate of approximately 0.25 mm/h. In contrast, green pepper samples showed minimal herbicide infiltration, likely owing to their hydrophobic cuticle barrier. Additionally, mice fed with herbicide-treated carrots exhibited detectable levels of herbicide in liver and kidney tissues. Conclusions: These findings highlight the utility of IDESI-MSI as a powerful analytical platform for the rapid evaluation of chemical migration and absorption in food and biological systems, with important implications for food safety and toxicological research. Full article
(This article belongs to the Special Issue Mass Spectrometry Imaging and Spatial Metabolomics)
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57 pages, 1430 KiB  
Review
A Fresh Perspective on Cyanobacterial Paralytic Shellfish Poisoning Toxins: History, Methodology, and Toxicology
by Zacharias J. Smith, Kandis M. Arlinghaus, Gregory L. Boyer and Cathleen J. Hapeman
Mar. Drugs 2025, 23(7), 271; https://doi.org/10.3390/md23070271 - 27 Jun 2025
Viewed by 1077
Abstract
Paralytic shellfish poisoning toxins (PSPTs) are a class of neurotoxins most known for causing illness from consuming contaminated shellfish. These toxins are also present in freshwater systems with the concern that they contaminate drinking and recreational waters. This review provides (1) a complete [...] Read more.
Paralytic shellfish poisoning toxins (PSPTs) are a class of neurotoxins most known for causing illness from consuming contaminated shellfish. These toxins are also present in freshwater systems with the concern that they contaminate drinking and recreational waters. This review provides (1) a complete list of the 84+ known PSPTs and important chemical features; (2) a complete list of all environmental freshwater PSPT detections; (3) an outline of the certified PSPT methods and their inherent weaknesses; and (4) a discussion of PSPT toxicology, the weaknesses in existing data, and existing freshwater regulatory limits. We show ample evidence of production of freshwater PSPTs by cyanobacteria worldwide, but data and method uncertainties limit a proper risk assessment. One impediment is the poor understanding of freshwater PSPT profiles and lack of commercially available standards needed to identify and quantify freshwater PSPTs. Further constraints are the limitations of toxicological data derived from human and animal model exposures. Unassessed mouse toxicity data from 1978 allowed us to calculate and propose toxicity equivalency factors (TEF) for 11-hydroxysaxitoxin (11-OH STX; M2) and 11-OH dcSTX (dcM2). TEFs for the 11-OH STX epimers were calculated to be 0.4 and 0.6 for 11α-OH STX (M2α) and 11β-OH STX (M2β), while we estimate that TEFs for 11α-OH dcSTX (dcM2α) and 11β-OH dcSTX (dcM2β) congeners would be 0.16 and 0.23, respectively. Future needs for freshwater PSPTs include increasing the number of reference materials for environmental detection and toxicity evaluation, developing a better understanding of PSPT profiles and important environmental drivers, incorporating safety factors into exposure guidelines, and evaluating the accuracy of the established no-observed-adverse-effect level. Full article
(This article belongs to the Section Marine Toxins)
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23 pages, 4903 KiB  
Article
Highly Effective mRNA-LNP Vaccine Against Respiratory Syncytial Virus (RSV) in Multiple Models
by Huarong Bai, Xueliang Yu, Yue Gao, Qin Li, Baigang Wen and Rongkuan Hu
Vaccines 2025, 13(6), 625; https://doi.org/10.3390/vaccines13060625 - 10 Jun 2025
Viewed by 1525
Abstract
Background: The transmembrane fusion (F) protein of RSV plays important roles in RSV pathogenesis as it mediates the fusion between the virus and the target cell membrane. During the fusion process, the F protein transits from a metastable state (prefusion, preF) to a [...] Read more.
Background: The transmembrane fusion (F) protein of RSV plays important roles in RSV pathogenesis as it mediates the fusion between the virus and the target cell membrane. During the fusion process, the F protein transits from a metastable state (prefusion, preF) to a stable state (postfusion, postF) after the merging of the virus and cell membranes. The majority of highly neutralizing antibodies induced by natural infection or immunization target the preF form, which makes it the preferred antigen for vaccine development. Methods: Here, we designed an effective RSV mRNA vaccine, STR-V003, consisting of mRNA encoding preF protein in lipid nanoparticles (LNPs). The immunogenicity, protection efficacy and toxicity were measured in multiple animal models. Results: STR-V003 demonstrated robust immunogenicity in both mice and cotton rats, inducing high levels of neutralizing antibodies and RSV preF-specific IgG antibodies and significantly reducing the RSV viral loads in the lung and nose tissue of challenged animals. In addition, STR-V003 did not show significant enhancement of lung pathology without causing vaccine-enhanced disease (VED). The repeated dose general toxicology studies and local tolerance studies of STR-V003 were evaluated in rats and non-human primate (NHP). Conclusions: STR-V003 demonstrates a favorable safety profile and induces robust protective immunity against RSV. Full article
(This article belongs to the Special Issue The Development of mRNA Vaccines)
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35 pages, 2537 KiB  
Review
Millettia speciosa and By-Products: A Comprehensive Review of Chemical Composition, Bioactivities, Safety, and Industrial Applications
by Juntai Chen and Wenyong Lou
Foods 2025, 14(12), 2035; https://doi.org/10.3390/foods14122035 - 9 Jun 2025
Viewed by 674
Abstract
Millettia speciosa (MS) is a traditional medicinal and edible plant with notable nutritional value and a wide range of biological activities. Recent studies have explored its chemical composition and pharmacological effects, particularly focusing on the potential utilization of its by-products. However, [...] Read more.
Millettia speciosa (MS) is a traditional medicinal and edible plant with notable nutritional value and a wide range of biological activities. Recent studies have explored its chemical composition and pharmacological effects, particularly focusing on the potential utilization of its by-products. However, a lack of integrated analysis has limited a comprehensive understanding of its functional value and industrial relevance. This review provides a critical overview of the major bioactive components of MS, such as flavonoids, phenolic acids, alkaloids, saponins, and polysaccharides, and highlights their antioxidant, lipid-lowering, antimicrobial, antidepressant, and immune-regulatory properties. In addition, the nutritional aspects of MS, including its protein, amino acid, and mineral contents, are discussed in detail. Safety evaluations based on existing toxicological and pharmacokinetic studies are also summarized. Furthermore, this work outlines the current and emerging applications of MS and its by-products in key industries: in the food sector as functional ingredients and nutritional supplements, in agriculture as biofertilizers and animal feed additives, and in cosmetics for their antioxidative and skin-protective effects. Finally, the review identifies current challenges and prospects for the industrial development of MS-based products across multiple domains. Full article
(This article belongs to the Section Food Nutrition)
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19 pages, 1331 KiB  
Article
Safety Toxicology Study of Reassortant Mopeia–Lassa Vaccine in Guinea Pigs
by Bradley S. Wahle, Peter Pushko, Katie Albanese, Dylan M. Johnson, Irina Tretyakova, Igor S. Lukashevich and Thomas Rudge
Future Pharmacol. 2025, 5(2), 26; https://doi.org/10.3390/futurepharmacol5020026 - 31 May 2025
Viewed by 625
Abstract
(1) Background: Mopeia–Lassa reassortant ML29 virus is an investigational, reassortant virus vaccine for the prevention of Lassa fever caused by Lassa virus (LASV). (2) Methods: The vaccine virus ML29-SF was prepared in Vero cells using a serum-free culture medium under Good Manufacturing Practice. [...] Read more.
(1) Background: Mopeia–Lassa reassortant ML29 virus is an investigational, reassortant virus vaccine for the prevention of Lassa fever caused by Lassa virus (LASV). (2) Methods: The vaccine virus ML29-SF was prepared in Vero cells using a serum-free culture medium under Good Manufacturing Practice. A 2-week repeat dose toxicity study was performed in guinea pigs under Good Laboratory Practice (GLP) regulations to assess the local and systemic toxicological effects. (3) Results: Following an intramuscular (IM) or subcutaneous (SC) injection of 104 PFU of ML29-SF LASV vaccine at the start of the study, with a second dose 15 days later, no toxicological response attributable to the vaccine was observed. Vaccine-related effects were not observed in any in-life or post-mortem parameter evaluated, including clinical observations, injection site observations, body temperature, body weight, food consumption, ophthalmology, immunology, hematology, clinical chemistry, gross anatomical pathology, organ weights, and histopathology. An immunogenic response, as measured by the elicitation of IgG antibodies against major LASV immunogens, nucleocapsid and glycoprotein precursor, was observed in all vaccine-treated animals prior to the booster dose (Study Day 15) which endured through the end of the study (Study Day 42). There was no evidence of viral shedding in any vaccinated animal. (4) Conclusions: Overall, this single-dose vaccine was locally and systemically well tolerated even after a two-dose repeat administration, confirming the high level of safety of ML29-SF vaccination and supporting the future evaluation of this LASV vaccine, including in clinical trials. Full article
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14 pages, 1759 KiB  
Article
Machine Learning on Toxicogenomic Data Reveals a Strong Association Between the Induction of Drug-Metabolizing Enzymes and Centrilobular Hepatocyte Hypertrophy in Rats
by Kazuki Ikoma, Takuomi Hosaka, Akira Ooka, Ryota Shizu and Kouichi Yoshinari
Int. J. Mol. Sci. 2025, 26(10), 4886; https://doi.org/10.3390/ijms26104886 - 20 May 2025
Viewed by 578
Abstract
Centrilobular hepatocyte hypertrophy is frequently observed in animal studies for chemical safety assessment. Although its toxicological significance and precise mechanism remain unknown, it is considered an adaptive response resulting from the induction of drug-metabolizing enzymes (DMEs). This study aimed to elucidate the association [...] Read more.
Centrilobular hepatocyte hypertrophy is frequently observed in animal studies for chemical safety assessment. Although its toxicological significance and precise mechanism remain unknown, it is considered an adaptive response resulting from the induction of drug-metabolizing enzymes (DMEs). This study aimed to elucidate the association between centrilobular hepatocyte hypertrophy and DME induction using machine learning on toxicogenomic data. Utilizing publicly available gene expression data and pathological findings from rat livers of 134 compounds, we developed six different types of machine learning models to predict the occurrence of centrilobular hepatocyte hypertrophy based on gene expression data as explanatory variables. Among these, a LightGBM-based model demonstrated the best performance with an accuracy of approximately 0.9. With this model, we assessed each gene’s contribution to predicting centrilobular hepatocyte hypertrophy using mean absolute SHAP values. The results revealed that Cyp2b1 had an extremely significant contribution, while other DME genes also displayed positive contributions. Additionally, enrichment analysis of the top 100 genes based on mean absolute SHAP values identified “Metabolism of xenobiotics by cytochrome P450” as the most significantly enriched term. In conclusion, the current results suggest that the induction of multiple DMEs, including CYP2B1, is crucial for the development of centrilobular hepatocyte hypertrophy. Full article
(This article belongs to the Special Issue Advanced Research in Biomolecular Design for Medical Applications)
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33 pages, 3748 KiB  
Systematic Review
Fungi-Based Bioproducts: A Review in the Context of One Health
by Thais Kato de Sousa, Adriane Toledo da Silva and Filippe Elias de Freitas Soares
Pathogens 2025, 14(5), 463; https://doi.org/10.3390/pathogens14050463 - 9 May 2025
Viewed by 1041
Abstract
Entomopathogenic fungus-based biopesticides are an excellent alternative to synthetic pesticides and are widely used in insect pest control. With the transformations of the agri-food system, it is important to consider the One Health approach, which recognizes that health threats are shared at the [...] Read more.
Entomopathogenic fungus-based biopesticides are an excellent alternative to synthetic pesticides and are widely used in insect pest control. With the transformations of the agri-food system, it is important to consider the One Health approach, which recognizes that health threats are shared at the interface between people, animals, plants, and the environment. The safety and environmental impact of fungi-based insecticides should be assessed comprehensively, taking into account not only their effects on non-target organisms and human health but also their environmental fate. This includes how these substances degrade, persist, or dissipate in soil, water, and air and their potential to bioaccumulate or leach into groundwater. Such assessments are essential to ensure that their long-term use does not pose unintended risks to ecosystems or public health. This systematic review aims to identify and analyze available studies on the potential One Health hazards associated with fungal biopesticides. A total of 134 articles were selected: 84 bioassay articles (63%), 36 case reports (27%), 10 field studies (7%), and 4 other types of studies (3%). Of these articles, 59 were studies on vertebrate animals and 65 studies on invertebrate animals, 6 studies on diverse organisms, 2 studies focused specifically on risk assessment for non-target organisms in the environment, while 2 other studies looked at the toxicological hazards associated with human exposure to the metabolites of the fungus present in air. The United States had the highest number of publications (33). Beauveria bassiana and Metarhizium anisopliae followed by the fungi Cordyceps fumosorosea (Paecilomyces fumosoroseus) and B. brongniartii were the most prevalent fungal species in the studies. This review highlights that case reports of infections in humans and other vertebrates by fungi are not related to the use of fungal biopesticides. A predominance of studies with bees was identified due to the importance of these insects as pollinators. The findings indicate that fungal biopesticides pose minimal risks when used appropriately. Nevertheless, the necessity for standardized safety assessments is emphasized. In order to ensure greater effectiveness, it is essential to develop unified protocols and bioassays with specific risk indicators aligned with the One Health approach. This includes evaluating potential effects on pollinators, vertebrate toxicity, and the environmental persistence of metabolites. In future research, the development of integrated guidelines that simultaneously consider human, animal, and environmental health is recommended. Full article
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20 pages, 2977 KiB  
Review
From Biosynthesis to Legislation: A Review of Hydroxytyrosol’s Biological Functions and Safety
by Zhong Wang, Ziteng Lei, Haijing Zhang, Zheng Liu, Wei Chen, Yan Jia, Ruoyu Shi and Chengtao Wang
Int. J. Mol. Sci. 2025, 26(10), 4470; https://doi.org/10.3390/ijms26104470 - 8 May 2025
Cited by 3 | Viewed by 1592
Abstract
Hydroxytyrosol (HT), a potent phenolic compound derived from olives, has attracted significant attention due to its exceptional antioxidant, anti-inflammatory, and antimicrobial properties. This review comprehensively examines recent advances in the synthesis, biological functions, safety profiles, and legal regulations of HT. We discuss both [...] Read more.
Hydroxytyrosol (HT), a potent phenolic compound derived from olives, has attracted significant attention due to its exceptional antioxidant, anti-inflammatory, and antimicrobial properties. This review comprehensively examines recent advances in the synthesis, biological functions, safety profiles, and legal regulations of HT. We discuss both natural and biotechnological synthesis routes, including enzyme-mediated, non-transgenic, and transgenic biosynthetic methods, highlighting recent innovations that have improved yield and purity. The review further explores the multifaceted biological activities of HT, ranging from its role in cardiovascular protection and neuroprotection to its anticancer and metabolic regulatory effects. Safety assessments from animal and human studies are analyzed, demonstrating low toxicity and favorable metabolic profiles at physiologically relevant doses. Additionally, we compare international regulatory frameworks from the United States, China, and the European Union, which underscore the compound’s safe use in food, pharmaceuticals, and cosmetics. Finally, the review outlines future research directions aimed at optimizing production methods, enhancing bioavailability, and addressing long-term toxicological outcomes, thereby reinforcing HT’s potential as a high-value functional ingredient in various industries. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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36 pages, 1680 KiB  
Review
Genotoxicity in Unconventional Mammalian Models of Wild, Urban, and Agricultural Ecosystems: A Systematic Review Under the One Health Approach
by Nora Bibiana M. Gorla, Mariela Nieves and Daniela Marisol Ferré
Genes 2025, 16(5), 525; https://doi.org/10.3390/genes16050525 - 29 Apr 2025
Cited by 1 | Viewed by 1253
Abstract
Background/Objectives: This systematic review evaluates unconventional mammalian models from wild, agricultural, and urban/domestic ecosystems for genotoxicity assessment under the One Health framework. Non-human primates (NHPs), cattle, and domestic dogs are analyzed as sentinel species due to their distinct environmental niches, unique human interactions, [...] Read more.
Background/Objectives: This systematic review evaluates unconventional mammalian models from wild, agricultural, and urban/domestic ecosystems for genotoxicity assessment under the One Health framework. Non-human primates (NHPs), cattle, and domestic dogs are analyzed as sentinel species due to their distinct environmental niches, unique human interactions, and species-specific traits. In conjunction with this, evidence is presented about the in vitro use of cells of these mammals for the genotoxicological evaluation of different chemical substances, such as veterinary drugs, environmental pollutants, and pesticides. The synthesis focuses on standardized genetic toxicology assays (e.g., chromosomal aberrations, micronucleus, comet assay) aligned with Organization for Economic Cooperation and Development (OECD) guidelines. Methods: A structured search of international literature identified studies employing OECD-compliant genotoxicity assays in NHPs, cattle, dogs, and others not listed in OECD. Data was categorized by species, assay type, chemical class evaluated, environmental context (wild, agricultural, urban), and merits of the papers. Results: NHPs, despite their phylogenetic proximity to humans, show limited genotoxicity data in contrast to biomedical research, which has been constrained by ethical concerns and fieldwork logistics. Cattle emerge as robust models in agricultural settings due to the abundance of studies on the genotoxic capacity of pesticides, veterinary drug, and environmental biomonitoring, with direct implications for food safety. Domestic dogs are recognized as powerful sentinels for human health due to shared exposomes, physiological similarities (e.g., shorter cancer latency), and reduced lifestyle confounders; however, genotoxicity studies in dogs remain sparse compared to chemical exposure monitoring or cancer research. Conclusions: This review advocates for expanded, integrated use of these models to address genotoxic threats across ecosystems, which would benefit both animal and human health. In the application of biomonitoring studies with sentinel animals, a critical gap persists: the frequent lack of integration between xenobiotic quantification in environmental and biological samples, along with genotoxicity biomarkers evaluation in sentinel populations, which hinders comprehensive environmental risk assessment. Full article
(This article belongs to the Collection Feature Papers in ‘Animal Genetics and Genomics’)
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