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18 pages, 3126 KB  
Article
The In Vitro Toxicity Profile of Nanoencapsulated Curcumin in a Chitosan–Alginate Gel Carrier Using Rabbit Lymphocytes: Preliminary Research
by Marta Kuchta-Gładysz, Joanna Wojciechowska-Puchałka, Anna Grzesiakowska-Dul, Michał Kmiecik, Karen Khachatryan and Gohar Khachatryan
Int. J. Mol. Sci. 2025, 26(17), 8577; https://doi.org/10.3390/ijms26178577 - 3 Sep 2025
Viewed by 242
Abstract
Curcumin is a natural bioactive compound of plant origin, characterised by a wide variety of properties that make it useful in numerous industries. Furthermore, due to its health-promoting properties, such as anti-inflammatory, antioxidant, and antimicrobial effects, it has found applications in medicine and [...] Read more.
Curcumin is a natural bioactive compound of plant origin, characterised by a wide variety of properties that make it useful in numerous industries. Furthermore, due to its health-promoting properties, such as anti-inflammatory, antioxidant, and antimicrobial effects, it has found applications in medicine and animal husbandry. Unfortunately, curcumin has low bioavailability; its hydrophobic nature means it is poorly absorbed through the gastrointestinal tract, and it is rapidly metabolised in the liver. In recent years, research has been conducted into adding nanoencapsulated active ingredients, such as curcumin, to animal feed. This research aims to improve the bioavailability and stability of these ingredients, extend their shelf life, and enhance their absorption. These effects are expected to improve overall animal health, increase production efficiency, and enhance the quality of animal products. However, a significant challenge remains: the irreversible aggregation and chemical instability of bioactive substances due to the hydrolysis of their polymeric encapsulants, which can lead to toxic effects. This study utilised peripheral whole blood from five Blanc de Termonde rabbits. In vitro cell exposure was conducted using three distinct concentrations of nanoencapsulated curcumin (C1–C3: 10, 5.0, and 2.5 µg/mL) and a control. Cytotoxicity was determined by assessing viability using trypan blue exclusion, the comet assay, and the micronucleus assay. The results indicated that all tested concentrations of nanocurcumin significantly decreased the viability of blood cells to approximately 1–9%. In contrast, the encapsulation matrices themselves were not toxic (results were statistically significant). In the comet assay, the nanocurcumin formulations were toxic at all concentrations, and the results were statistically significant. Following exposure, the micronucleus assay revealed cell damage and a high percentage of apoptotic cells (up to 30% for Cur1 at 10 ug/mL). A significant number of binucleated cells with two micronuclei (BNCs + 2MN) were also observed, again for Cur1. In view of the considerable variation in the results from the individual tests, it is advisable to repeat the research using different matrix forms and concentrations of curcumin. Full article
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27 pages, 425 KB  
Review
Green Preservation Strategies: The Role of Essential Oils in Sustainable Food Preservatives
by Sara Diogo Gonçalves, Maria das Neves Paiva-Cardoso and Ana Caramelo
Sustainability 2025, 17(16), 7326; https://doi.org/10.3390/su17167326 - 13 Aug 2025
Viewed by 512
Abstract
Essential oils (EOs) have gained increasing attention as natural alternatives to synthetic food preservatives due to their broad-spectrum antimicrobial, antioxidant, and antigenotoxic properties. Derived from aromatic plants, EOs possess complex chemical compositions rich in bioactive compounds such as terpenes, phenolics, and aldehydes, which [...] Read more.
Essential oils (EOs) have gained increasing attention as natural alternatives to synthetic food preservatives due to their broad-spectrum antimicrobial, antioxidant, and antigenotoxic properties. Derived from aromatic plants, EOs possess complex chemical compositions rich in bioactive compounds such as terpenes, phenolics, and aldehydes, which contribute to their effectiveness against foodborne pathogens, oxidative spoilage, and genotoxic contaminants. This review provides a comprehensive examination of the potential of EOs in food preservation, highlighting their mechanisms of action, including membrane disruption, efflux pump inhibition, and reactive oxygen species scavenging. Standard assays such as disk diffusion, MIC/MBC, time-kill kinetics, and comet and micronucleus tests are discussed as tools for evaluating efficacy and safety. Additionally, the use of EOs in diverse food matrices and the reduction in reliance on synthetic additives support cleaner-label products and improved consumer health. The review also examines the sustainability outlook, highlighting the potential for extracting EOs from agricultural byproducts, their integration into green food processing technologies, and alignment with the circular economy and the Sustainable Development Goals. Despite promising results, challenges remain in terms of sensory impact, regulatory approval, and dose optimization. Overall, EOs represent a multifunctional and sustainable solution for modern food preservation systems. Full article
(This article belongs to the Special Issue Future Trends in Food Processing and Food Preservation Techniques)
15 pages, 524 KB  
Systematic Review
Association Between Maternal Diet and Frequency of Micronuclei in Mothers and Newborns: A Systematic Review
by Anny Cristine de Araújo, Priscila Kelly da Silva Bezerra do Nascimento, Marília Cristina Santos de Medeiros, Raul Hernandes Bortolin, Ricardo Ney Cobucci and Adriana Augusto de Rezende
Nutrients 2025, 17(15), 2535; https://doi.org/10.3390/nu17152535 - 1 Aug 2025
Viewed by 425
Abstract
Background/Objectives: The effect of diet on maternal and infant genetic levels has been reported in the literature. Diet-associated DNA damage, such as the presence of micronuclei (MN), may be related to an increased risk of developing chronic diseases such as cancer. There is [...] Read more.
Background/Objectives: The effect of diet on maternal and infant genetic levels has been reported in the literature. Diet-associated DNA damage, such as the presence of micronuclei (MN), may be related to an increased risk of developing chronic diseases such as cancer. There is particular concern regarding this damage during pregnancy, as it may affect the newborn (NB). Thus, this review aims to summarize the primary evidence of the impact of diet on the frequency of MN in the mother–infant population. Methods: Five databases (PubMed, Embase, Web of Science, Scopus, and ScienceDirect) were used to search for observational studies. Google Scholar and manual searching were required to perform the “gray literature” search. Results: The search strategy retrieved 1418 records. Of these, 13 were read in full and 5 were included in the review. Most studies were of the cohort type (n = 4) and were carried out in the European region. A total of 875 pregnant women and 238 newborns were evaluated. Despite insufficient evidence to confirm that diet changes the frequency of MN, the included studies found possible effects from the consumption of fried red meat and processed meats and the adequate consumption of vegetables and polyunsaturated fats. Conclusions: Future research is needed in order to understand the effects of diet on genetic stability and to obtain evidence to help plan public policies on food and nutrition or reinforce protective dietary patterns for this and future generations. Full article
(This article belongs to the Section Nutrition in Women)
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16 pages, 3457 KB  
Article
Association Between Genotoxic Effects of Ageing Dental Restorations and Micronuclei in Oral Mucosal Cells
by Csilla Benedek, Bernadette Kerekes-Máthé, Zsuzsanna Bardocz-Veres, Boglárka Szabó, Alina Iacob, Alexandra Stoica, Timea Dako, Mónika Kovács, Lóránd Dénes and Liana Bereșescu
Medicina 2025, 61(8), 1363; https://doi.org/10.3390/medicina61081363 - 28 Jul 2025
Viewed by 350
Abstract
Background and Objectives: Dental restorations can be composed of various materials, including amalgams and methacrylate-based resins. The health risks associated with the components of the restorative materials have always been a concern, even more so with the ageing of the restorations. As [...] Read more.
Background and Objectives: Dental restorations can be composed of various materials, including amalgams and methacrylate-based resins. The health risks associated with the components of the restorative materials have always been a concern, even more so with the ageing of the restorations. As the micronucleus (MN) test is a standard, accessible, and minimally invasive technique for studying the genotoxic effect of clastogenic chemicals on oral mucosal cells, the current study was conducted to determine the frequency and morphological properties of MN in the exfoliated oral mucosal cells. Materials and Methods: A total of 115 aged composite and amalgam restorations were included in this study. Epithelial cells were collected from the gingival tissue adjacent to the restorations of each patient and stained with a hematoxylin–eosin (HE) stain. After evaluation of the slides, the results were subjected to statistical analysis using Chi-square tests. The level of significance was set at 0.05. Results: The mean number of MN was significantly lower for composite restorations compared to amalgam restorations. There were no statistically significant differences between composite restorations aged 1–5 years, 5–10 years, over 10 years, and amalgam restorations aged over 10 years in the location (p = 0.11), staining (p = 0.11), or morphological characteristics (p = 0.18) of the MN. Conclusions: Despite the main limitation of this study, the lack of a control group, our results suggest that long-term exposure to restorative fillings and the ageing of these materials can cause DNA damage locally in the adjacent sites of oral cavity. Full article
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22 pages, 2276 KB  
Article
Phytochemical Profile, Toxicological Screening, Antitumor Activity, and Immunomodulatory Response of Saline Extract from Euphorbia hirta L. Leaves
by Jainaldo Alves da Costa, Amanda de Oliveira Marinho, Robson Raion de Vasconcelos Alves, Matheus Cavalcanti de Barros, Isabella Coimbra Vila Nova, Sheilla Andrade de Oliveira, João Victor de Oliveira Alves, Vitória Figueiredo Silva, Magda Rhayanny Assunção Ferreira, Alisson Macário de Oliveira, Luiz Alberto Lira Soares, Carina Scanoni Maia, Fernanda das Chagas Ângelo Mendes Tenório, Virgínia Maria Barros de Lorena, Roberto Araújo Sá, Thiago Henrique Napoleão, Leydianne Leite de Siqueira Patriota, Maria Lígia Rodrigues Macedo and Patrícia Maria Guedes Paiva
Molecules 2025, 30(15), 3105; https://doi.org/10.3390/molecules30153105 - 24 Jul 2025
Viewed by 721
Abstract
Euphorbia hirta L. is traditionally used to treat tumors and has demonstrated anticancer effects. This study evaluated the phytochemical composition, toxicity, and antitumor activity of saline extract (SE) from E. hirta leaves in mice. Phytochemical analysis included thin layer chromatography, high-performance liquid chromatography, [...] Read more.
Euphorbia hirta L. is traditionally used to treat tumors and has demonstrated anticancer effects. This study evaluated the phytochemical composition, toxicity, and antitumor activity of saline extract (SE) from E. hirta leaves in mice. Phytochemical analysis included thin layer chromatography, high-performance liquid chromatography, and quantification of phenols, flavonoids, and proteins. Acute toxicity (2000 mg/kg) assessed mortality, hematological, biochemical, histological parameters, water/feed intake, and body weight. Genotoxicity was evaluated via comet and micronucleus assays. Antitumor activity was tested in vitro and in vivo on sarcoma 180. SE contained 107.3 mg GAE/g phenolics and 22.9 mg QE/g flavonoids; the presence of gallic and ellagic acids was detected. Protein concentration was 12.16 mg/mL with lectin activity present. No mortality, organ damage, or genotoxic effects occurred in toxicity tests. SE demonstrated in vitro cytotoxicity against sarcoma cells (IC50: 10 µg/mL). In vivo, SE (50–200 mg/kg) reduced tumor weight by 70.2–72.3%. SE modulated IL-2, IL-4, IL-6, IL-17, IFN-γ, and TNF-α in tumor environment. Tumors showed inflammatory infiltrate, necrosis, and fibrosis after treatment. These findings position the extract as a promising candidate for further development as a safe, plant-based antitumor agent. Full article
(This article belongs to the Special Issue Natural Products in Anticancer Activity: 2nd Edition)
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23 pages, 9320 KB  
Article
Evaluation of the Cytotoxicity, Genotoxicity and Acute Oral Toxicity of Thymus longicaulis subsp. chaubardii (Rchb.f.) Jalas
by Ayfer Beceren, Ayse Nur Hazar-Yavuz, Ozlem Bingol Ozakpinar, Duygu Taskin, Ismail Senkardes, Turgut Taskin, Ozlem Tugçe Cilingir-Kaya, Ahmad Kado, Elif Caliskan Salihi and Hatice Kubra Elcioglu
Pharmaceuticals 2025, 18(7), 1037; https://doi.org/10.3390/ph18071037 - 12 Jul 2025
Viewed by 586
Abstract
Background/Objectives: Thymus longicaulis subsp. chaubardii (TL) (Rchb.f.) Jalas is widely used in traditional Turkish medicine for respiratory, digestive and uro-genital disorders. The aim of this study was to determine its phytochemical profile and to evaluate its cytotoxic, genotoxic and acute oral toxicity [...] Read more.
Background/Objectives: Thymus longicaulis subsp. chaubardii (TL) (Rchb.f.) Jalas is widely used in traditional Turkish medicine for respiratory, digestive and uro-genital disorders. The aim of this study was to determine its phytochemical profile and to evaluate its cytotoxic, genotoxic and acute oral toxicity effects. Methods: The phenolic composition of the methanolic extract was determined by HPLC-DAD. Cytotoxicity and genotoxicity were evaluated in NIH3T3 cells using MTT, comet and micronucleus assays. Acute toxicity was evaluated in rats at doses of 300 and 2000 mg/kg body weight according to the OECD Guideline 420. Results: Rosmarinic acid (87.37 ± 5.39 µg/mg) was the major phenolic compound. TL extract showed >90% cell viability at 50–200 µg/mL, indicating no cytotoxicity. Comet assay revealed a slight increase in DNA damage at 100–200 µg/mL (p < 0.001), though significantly lower than the H2O2 group (p < 0.001). No significant (p > 0.05) effect was observed in the micronucleus assay between the treated groups. In rats, TL extract caused no mortality or behavioral changes over 14 days. No significant differences were observed in body or organ weights. Hematologically, platelet count increased (p < 0.001) and eosinophils decreased (p < 0.01 and p < 0.001). Biochemical tests showed lower ALT and AST levels (p < 0.01 and p < 0.05, respectively) and significantly decreased triglycerides in the high-dose group (p < 0.001). Histopathological examination showed no organ damage. Conclusions: The results of this study indicate that TL methanol extract is non-toxic up to 2000 mg/kg and exhibits no significant cytotoxic or genotoxic effects. These findings support its safe use and traditional medicinal value. Full article
(This article belongs to the Section Natural Products)
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13 pages, 1132 KB  
Article
Evaluating the Cytotoxic, Genotoxic, and Toxic Potential of Pyrolytic Tire Char Using Human Lymphocytes and a Bacterial Biosensor
by Ioanna Efthimiou, Margarita Dormousoglou, Lambrini Giova, Dimitris Vlastos, Stefanos Dailianis, Maria Antonopoulou and Ioannis Konstantinou
Toxics 2025, 13(7), 582; https://doi.org/10.3390/toxics13070582 - 12 Jul 2025
Viewed by 410
Abstract
Waste tires (WTs) constitute a potentially significant source of pollution, and the large quantities that are disposed of require proper handling. Pyrolysis has emerged as an environmentally friendly and effective method for WT treatment. In the present study, the cyto-genotoxic and toxic effects [...] Read more.
Waste tires (WTs) constitute a potentially significant source of pollution, and the large quantities that are disposed of require proper handling. Pyrolysis has emerged as an environmentally friendly and effective method for WT treatment. In the present study, the cyto-genotoxic and toxic effects of untreated and acid-treated pyrolytic tire char (PTCUN and PTCAT, respectively) were investigated. The cytokinesis block micronucleus (CBMN) assay, using human lymphocytes, and the Aliivibrio fischeri bioluminescence assay were used for the assessment of cyto-genotoxicity and ecotoxicity, respectively. According to the results, both PTCUN and PTCAT exhibited genotoxicity at all concentrations tested (2.5, 5, and 10 μg mL−1), which was more pronounced in the case of PTCAT. Cytotoxicity induction was reported for PTCUN and PTCAT at all concentrations. Both demonstrated a relatively low potential for ecotoxicity induction against A. fischeri. Since the cyto-genotoxic and toxic effects of PTCAT seemed to be more pronounced, the toxic profile of tire char should be investigated in depth before selecting the appropriate applications, thereby avoiding detrimental effects in the environment and humans alike. Full article
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17 pages, 1126 KB  
Article
Argovit™ Silver Nanoparticles Mitigate Sodium Arsenite-Induced Cytogenotoxicity Effects in Cultured Human Lymphocytes
by María del Carmen Jauregui Romo, Balam Ruiz Ruiz, Francisco Casilas-Figueroa, Nayeli Guadalupe Girón Vázquez, Roberto Luna Vázquez Gómez, Olivia Torres-Bugarín, Idalia Yazmín Castañeda Yslas, Alexey Pestryakov, Nina Bogdanchikova and María Evarista Arellano García
Toxics 2025, 13(7), 539; https://doi.org/10.3390/toxics13070539 - 27 Jun 2025
Viewed by 863
Abstract
Exposure to arsenic, a known environmental and occupational genotoxicant, poses significant health risks. Identifying agents capable of mitigating its effects is crucial for public health. This study evaluates the protective potential of Argovit™ silver nanoparticles (AgNPs) against cytotoxic and genotoxic damage induced by [...] Read more.
Exposure to arsenic, a known environmental and occupational genotoxicant, poses significant health risks. Identifying agents capable of mitigating its effects is crucial for public health. This study evaluates the protective potential of Argovit™ silver nanoparticles (AgNPs) against cytotoxic and genotoxic damage induced by sodium arsenite in ex vivo cultured human lymphocytes obtained from the whole blood of healthy donors. Lymphocytes were exposed to sodium arsenite (3.7 × 10−3 µg/mL) and Argovit™ AgNPs (3.6 × 10−3 µg/mL). The cytokinesis-block micronucleus (CBMN) assay was performed using a modified 144 h protocol to assess delayed effects across two cell cycles. Four groups were analyzed: untreated control, sodium arsenite only, AgNPs only, and sodium arsenite followed by AgNPs. Arsenite exposure increased cytotoxic and genotoxic biomarkers. In contrast, post-treatment with AgNPs significantly reduced these effects. All treatments were performed in duplicate, and data were analyzed using the Kruskal–Wallis test with Dunn’s post hoc comparison (p < 0.05). Statistical analysis confirmed the antigenotoxic and cytoprotective properties of Argovit™. These findings support its potential application as a mitigating agent in scenarios of environmental or occupational exposure to genotoxic compounds. Full article
(This article belongs to the Section Human Toxicology and Epidemiology)
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18 pages, 1864 KB  
Article
Effect of Chronic Administration of Justicia secunda Vahl in Mice Diabetized with Streptozotocin
by Tomás Fregoso-Aguilar, Perla Xóchitl Escamilla-Ramírez, Dulce E. Nicolás-Álvarez, Jorge Alberto Mendoza-Pérez, Eduardo Osiris Madrigal-Santillán, Judith Margarita Tirado-Lule, Elda Victoria Rodríguez-Negrete, Eduardo Madrigal-Bujaidar, Isela Álvarez-González, Gabriela Ibáñez-Cervantes, Ángel Morales-González and José A. Morales-Gonzalez
Diabetology 2025, 6(6), 56; https://doi.org/10.3390/diabetology6060056 - 18 Jun 2025
Viewed by 661
Abstract
Certain pharmacological properties of the methanolic extract of Justicia secunda Vahl leaves (Acanthaceae) were evaluated in Streptozotocin (STZ)-treated albino mice to confirm whether it could be considered an alternative candidate for the treatment of diabetes. Using qualitative phytochemistry, alkaloids, flavonoids, and [...] Read more.
Certain pharmacological properties of the methanolic extract of Justicia secunda Vahl leaves (Acanthaceae) were evaluated in Streptozotocin (STZ)-treated albino mice to confirm whether it could be considered an alternative candidate for the treatment of diabetes. Using qualitative phytochemistry, alkaloids, flavonoids, and tannins were detected. In an in vitro DPPH antioxidant activity test, high extract concentrations inhibited the radical by 90% during the first minutes of the reaction. The extract presented a slight genoprotective effect on mouse peripheral blood during the last days of the micronucleus test. Oral administration of the extract at a high dose every two days for 6 weeks caused a hypoglycemic effect in STZ-treated mice, protection against weight loss, and decreased blood triglyceride levels from week 3 of treatment. These effects could be mediated by the antioxidant activity of the detected metabolites and, perhaps, by an inhibitory effect on intestinal α-glucosidase. This renders J. secunda a good candidate for the long-term alternative treatment of diabetes without abandoning allopathic therapy. Full article
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21 pages, 2171 KB  
Article
Commiphora leptophloeos Bark Decoction: Phytochemical Composition, Antioxidant Capacity, and Non-Genotoxic Safety Profile
by José Rafael da Silva Araujo, Rafael de Felício, Camila Marinho da Silva, Palloma Lima de Oliveira, Silvany de Sousa Araújo, Laís Roberta Deroldo Sommaggio, Adriana Fabiana Corrêa da Silva, Paulo Henrique Valença Nunes, Bruno Oliveira de Veras, Erwelly Barros de Oliveira, Jaciana dos Santos Aguiar, Maria Aparecida Marin-Morales, Daniela Barretto Barbosa Trivella, Ana Maria Benko-Iseppon, Márcia Vanusa da Silva and Ana Christina Brasileiro-Vidal
Pharmaceuticals 2025, 18(6), 863; https://doi.org/10.3390/ph18060863 - 10 Jun 2025
Viewed by 670
Abstract
Background: Commiphora leptophloeos has long been used in Latin American folk medicine for the treatment of respiratory and gastrointestinal disorders. Therefore, toxicological and phytochemical investigations are required to assess the safety and support the evidence-based use of its bark in medicinal applications. [...] Read more.
Background: Commiphora leptophloeos has long been used in Latin American folk medicine for the treatment of respiratory and gastrointestinal disorders. Therefore, toxicological and phytochemical investigations are required to assess the safety and support the evidence-based use of its bark in medicinal applications. This study aimed to evaluate the aqueous bark extract of C. leptophloeos, focusing on its chemical composition and its antioxidant, cytotoxic, and genotoxic properties. Methods: The aqueous extract was obtained by decoction of dried bark samples. Phytochemical characterization was conducted using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS), and data were processed using the NP3 MS Workflow 1.1.4 software, allowing for the annotation of key secondary metabolites. Antioxidant activity was assessed through multiple in vitro assays, including DPPH, ABTS, phosphomolybdenum, and reducing power tests. Cytotoxicity was evaluated using the MTT assay, while genotoxicity was investigated through the Ames test and micronucleus assay. Results: Phytochemical analysis revealed several flavonoids, with procyanidin B2 annotated as a major compound. The extract exhibited strong antioxidant activity, with EC50 values of 5.43 μg/mL (DPPH), 12.40 μg/mL (ABTS), 35.20 μg/mL (phosphomolybdenum), and 31.27 μg/mL (reducing power). The MTT assay showed no cytotoxic effects at concentrations up to 6400 μg/mL. Furthermore, both the Ames and micronucleus assays showed the absence of genotoxic effects at concentrations up to 1600 μg/plate and 400 μg/mL, respectively. Conclusions: The aqueous bark extract of C. leptophloeos demonstrates strong antioxidant potential and a favorable safety profile, with no detectable cytotoxicity or genotoxicity at concentrations effective in antioxidant assays. Further studies are recommended to confirm and validate its traditional medicinal properties using appropriate in vivo models, followed by pre-clinical evaluations. Full article
(This article belongs to the Special Issue Pharmacologically Active Compounds from Plants)
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12 pages, 315 KB  
Article
A Regulatory-Compliant Genotoxicity Study of a Mixture of C60 and C70 Fullerenes Dissolved in Olive Oil Using the Mammalian Micronucleus Test
by Fathi Moussa
Nanomaterials 2025, 15(11), 870; https://doi.org/10.3390/nano15110870 - 5 Jun 2025
Viewed by 1256
Abstract
Although they show great promise in the medical field, the safety of fullerenes—discovered forty years ago—is still uncertain, according to regulatory experts at the European Scientific Committee on Consumer Safety. This is a major obstacle to progress in the field. Meanwhile, oily solutions [...] Read more.
Although they show great promise in the medical field, the safety of fullerenes—discovered forty years ago—is still uncertain, according to regulatory experts at the European Scientific Committee on Consumer Safety. This is a major obstacle to progress in the field. Meanwhile, oily solutions of fullerenes intended for human and pet consumption can be purchased online, without any marketing authorization. Therefore, to avoid any potential public health issues, regulatory-compliant preclinical studies on fullerene oily solutions are urgently needed. We present the first in vivo genotoxicity study of a C60/C70 fullerene mixture (4.1/1, w/w) dissolved in extra virgin olive oil (0.8 mg/mL). The study was conducted using the Mammalian Micronucleus Test (MMT) in an independent GLP-laboratory, in compliance with the OECD and EPA guidelines. The MMT was performed on NMRI mice following the oral administration of fullerenes at doses of up to 3.6 mg/kg. This dose is almost the maximum dose that can be administered to rodents. The data obtained clearly show that fullerene oily solutions have no genotoxic activity under these conditions. This should pave the way for further regulatory investigations of fullerene oily solutions. Full article
(This article belongs to the Special Issue Carbon-Based Nanomaterials for Biomedicine Applications)
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12 pages, 1801 KB  
Article
New Synthetic Opioids: What Do We Know About the Mutagenicity of Brorphine and Its Analogues?
by Monia Lenzi, Sofia Gasperini, Sabrine Bilel, Giorgia Corli, Francesca Rombolà, Patrizia Hrelia and Matteo Marti
Int. J. Mol. Sci. 2025, 26(11), 5084; https://doi.org/10.3390/ijms26115084 - 26 May 2025
Viewed by 661
Abstract
Since 2019, a growing number of structurally diverse, non-Fentanyl-related novel synthetic opioids (NSOs) have emerged, but little is still known on the toxic profile of several of the molecules belonging to this class. Regarding long-term toxicity, few studies have investigated the genotoxic potential [...] Read more.
Since 2019, a growing number of structurally diverse, non-Fentanyl-related novel synthetic opioids (NSOs) have emerged, but little is still known on the toxic profile of several of the molecules belonging to this class. Regarding long-term toxicity, few studies have investigated the genotoxic potential of NSOs, and no genotoxic data at all are available for the subclass of Brorphine-like benzimidazolone opioids. To deepen and broaden our understanding of their toxicological profile, this study was aimed at evaluating the genotoxicity of Brorphine and four of its analogues (Orphine, Fluorphine, Chlorphine and Iodorphine) on human lymphoblastoid TK6 cells employing a flow cytometric protocol of the “In Vitro Mammalian Cell Micronucleus (MN) test”. The results show a statistically significant MNi increase for Fluorphine, Chlorphine and Iodorphine, but not for Brorphine and Orphine, demonstrating for the first three the ability to induce chromosomal damage. Afterwards, Brorphine and Orphine were tested on TK6 cells also in the presence of an exogenous metabolic activation system (S9 mix) to consider the possible genotoxic hazard posed by their metabolites as well. Also, under this experimental condition, no statistically significant increase in the MNi frequency was detected. Full article
(This article belongs to the Section Molecular Toxicology)
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20 pages, 2995 KB  
Article
Genotoxic Effects of Chromium(III) and Cobalt(II) and Their Mixtures on the Selected Cell Lines
by Katarzyna Czarnek, Małgorzata Tatarczak-Michalewska, Eliza Blicharska, Andrzej K. Siwicki and Ryszard Maciejewski
Int. J. Mol. Sci. 2025, 26(11), 5056; https://doi.org/10.3390/ijms26115056 - 24 May 2025
Viewed by 2615
Abstract
Cr(III) and Co(II) can be potentially toxic to cells and induce a number of morphological and biochemical changes. These metals are widely used in many industries and can cause environmental pollution. They are the components of dietary supplements, vitamin and mineral products, and [...] Read more.
Cr(III) and Co(II) can be potentially toxic to cells and induce a number of morphological and biochemical changes. These metals are widely used in many industries and can cause environmental pollution. They are the components of dietary supplements, vitamin and mineral products, and energy drinks. Moreover, these metals are used in dentistry and orthopedics as components of implants. Data about the mechanism of genotoxic effects of Cr(III) and Co(II) are still incomplete. The aim of this study was to analyze the genotoxic effects of chromium(III) and cobalt(II) and their mixtures on two cell lines: mouse embryo fibroblast cell line BALB/3T3 and human hepatocellular carcinoma cell line G2 (HepG2). The BALB/3T3 and HepG2 cell lines were exposed to chromium chloride and cobalt chloride at concentrations ranging from 100 to 1400 µM. The genotoxicity assays used were the comet and micronucleus assays. On the basis of the results obtained from the first stage of the research, the concentrations of elements were selected in order to determine the interactions between them. The tested cell lines were treated with mixtures of the following compounds: chromium chloride at the concentration of 200 μM and cobalt chloride at the concentration of 1000 μM or chromium chloride at the concentration of 1000 μM and cobalt chloride at the concentration of 200 μM in the genotoxicity assays. This study shows that both cobalt(II) and chromium(III) cause genotoxic effects in the BALB/3T3 and HepG2 cell lines. A statistically significant increase in the percentage of comets was observed with increasing concentrations of Co(II) and Cr(III) compared to the control. A statistically significant induction of chromosomal aberrations was also observed in the micronucleus test. Moreover, chromium(III) at a concentration of 200 µM had a protective effect against the toxic concentration of cobalt(II) at a concentration of 1000 µM. The toxic effect of cobalt chloride and chromium chloride was confirmed in this study. Further research is needed on the genotoxic effects of cobalt(II) and chromium(III), especially due to the growing popularity of dietary supplements containing compounds of these metals and doubts as to the safety of their use. Full article
(This article belongs to the Special Issue Molecular Mechanism in DNA Replication and Repair)
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15 pages, 3838 KB  
Article
Extended Toxicity, Genotoxicity, and Mutagenicity of Combination of pBudK-coVEGF-coANG and pBudK-coGDNF Plasmids in Preclinical Trials
by Igor V. Samatoshenkov, Alexander M. Aimaletdinov, Elena Y. Zakirova, Egan L. Kalmykov, Rustam Khodzhibaev, Yulia M. Samatoshenkova, Ilnur M. Ganiev, Marat S. Kadyrov and Yana O. Mukhamedshina
Biomedicines 2025, 13(5), 1223; https://doi.org/10.3390/biomedicines13051223 - 18 May 2025
Viewed by 650
Abstract
Chronic lower limb ischemia is a debilitating condition, particularly prevalent among elderly patients and individuals ineligible for revascularization procedures. Gene therapy aimed at promoting therapeutic angiogenesis presents a promising alternative treatment strategy. Objectives: This study evaluated the preclinical safety of a gene therapy [...] Read more.
Chronic lower limb ischemia is a debilitating condition, particularly prevalent among elderly patients and individuals ineligible for revascularization procedures. Gene therapy aimed at promoting therapeutic angiogenesis presents a promising alternative treatment strategy. Objectives: This study evaluated the preclinical safety of a gene therapy drug composed of the plasmids pBudK-coVEGF-coANG and pBudK-coGDNF in laboratory animals. Safety assessment followed a single intramuscular injection at a dose 30 times higher than the proposed therapeutic level. Methods: Acute toxicity was monitored over a 24-h period. Genotoxicity was assessed using the micronucleus test at doses of 200, 1000, and 5000 μg/kg. Bone marrow cytology was analyzed to detect hematopoietic toxicity. Delayed toxicity was evaluated over a two-week recovery period. Results: No signs of acute toxicity were observed, even at the highest dose. The micronucleus test revealed no genotoxic effects, with no significant increase in micronucleated polychromatic erythrocytes compared to control groups. Bone marrow erythroblast parameters remained within normal physiological ranges. Additionally, no delayed adverse effects were detected during the recovery period. Conclusions: The gene therapy drug demonstrated a favorable preclinical safety profile, exhibiting no evidence of toxicity or genotoxicity, even at substantially elevated doses. These findings support the continued development of this therapy as a potential treatment for chronic lower limb ischemia in patients who are not candidates for surgical intervention. Full article
(This article belongs to the Section Gene and Cell Therapy)
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46 pages, 1292 KB  
Review
Genotoxicity of Coffee, Coffee By-Products, and Coffee Bioactive Compounds: Contradictory Evidence from In Vitro Studies
by Maryam Monazzah and Dirk W. Lachenmeier
Toxics 2025, 13(5), 409; https://doi.org/10.3390/toxics13050409 - 18 May 2025
Cited by 1 | Viewed by 1258
Abstract
Coffee and coffee by-products, such as coffee cherries, coffee flowers, coffee leaves, green beans, roasted coffee, instant coffee, spent coffee grounds, and silverskin, contain a complex mixture of bioactive compounds that may exhibit both genotoxic and antimutagenic effects. This article evaluates in vitro [...] Read more.
Coffee and coffee by-products, such as coffee cherries, coffee flowers, coffee leaves, green beans, roasted coffee, instant coffee, spent coffee grounds, and silverskin, contain a complex mixture of bioactive compounds that may exhibit both genotoxic and antimutagenic effects. This article evaluates in vitro studies on the genotoxic potential of coffee and coffee by-products, with a focus on different preparation methods, roasting processes, and key chemical constituents. Furthermore, given the growing interest in utilizing coffee by-products for novel food applications, this review sought to identify knowledge gaps regarding their safety. The impact of metabolic activation, particularly the role of enzymatic detoxification and bioactivation, was examined to better understand the effects on genetic material. The findings suggest that while certain compounds in coffee can induce DNA damage under specific conditions, the overall evidence does not indicate a significant genotoxic risk to consumers. However, further studies, particularly in vivo and human studies, appear necessary to ensure the requirements of novel food applications for some coffee by-products. Full article
(This article belongs to the Section Agrochemicals and Food Toxicology)
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