Search Results (687)

Iodine-based antimicrobial materials are widely considered for biomedical applications due to their broad-spectrum antimicrobial activity; however, their potential genotoxicity requires systematic evaluation prior to clinical use. The aim of this study was to assess the genotoxic potential of a dextrin–polyvinyl alcohol–iodine (D/PVA/I-1) complex in accordance with OECD guidelines. Genotoxicity was evaluated in vitro using two complementary assays: the mammalian cell micronucleus test (OECD TG 487) in L5178Y TK^+/− cells and the bacterial reverse mutation assay (Ames test, OECD TG 471) using Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA, both in the presence and absence of metabolic activation (S9). In the micronucleus assay, no statistically significant increase in micronucleus frequency was observed at concentrations ranging from 0.039 to 0.625 mg/mL compared with the negative control. In the Ames test, no increase in revertant colony numbers was detected in any tested bacterial strain at concentrations up to 1250 μg/plate. At higher concentrations, pronounced cytotoxic and bactericidal effects were observed without evidence of mutagenic activity. Overall, the results demonstrate that the D/PVA/I-1 complex does not exhibit genotoxic or mutagenic potential under the tested in vitro conditions, indicating a favorable genetic safety profile and supporting further preclinical evaluation for potential biomedical applications. Full article

This article reports on the synthesis and characterization of the properties of ceramic powders and aerogels of rare earths using the Sc₂O₃:Eu₂O₃ system synthesized through the sol–gel method, as well as on the toxicological effects of the cytokinesis-block micronucleus cytome assay (CBMC). A sol–gel variant using epoxide-assisted gelling and supercritical CO₂ drying was employed to produce the aerogels. In vitro CBMCs were employed to assess the genotoxic and cytotoxic effects of the materials’ dosages and inherent properties. The morphology of the powders and aerogels consisted of agglomerates of irregularly shaped particles. At the same time, structural analysis revealed crystal sizes of 16 and 10 nm, respectively, for the ceramic powders and aerogels, in which microplastic deformations were observed. The cubic crystalline structure of the Sc₂O₃:Eu₂O₃ system remained unchanged. However, applying CBMC and observing the genotoxic and cytotoxic effects of the nanoparticles revealed that the main genotoxic xenobiotic agent was the aerogel. The primary mode of cellular death was necrosis, suggesting that reactive oxygen species might have been involved in the genotoxic and cytotoxic damage. Full article

Atriplex halimus is a medicinal plant traditionally used for various therapeutic purposes. This study evaluated the antioxidant, anti-inflammatory, cytotoxic, genotoxic, and anti-arthritic activities of the A. halimus aqueous extract (AHA). Anti-arthritic effects were investigated in Complete Freund’s Adjuvant (CFA)-induced arthritic rats treated with AHA (150 or 300 mg/kg) for 21 days. AHA significantly reduced paw swelling and arthritis severity and improved body weight, while a non-significant reduction in spleen enlargement was observed. Hematological and biochemical parameters were restored toward normal values, indicating anti-inflammatory, hepatoprotective, and nephroprotective effects. The extract also reduced oxidative stress by decreasing nitric oxide (NO) and malondialdehyde (MDA) levels and increasing glutathione (GSH) content and catalase (CAT) activity. Histopathological examination confirmed reduced inflammatory infiltration and protection against bone damage. Phytochemical analysis revealed polyphenols, flavonoids, and tannins, consistent with its antioxidant activity in DPPH, ABTS, CUPRAC, and o-phenanthroline assays. AHA also showed anti-inflammatory activity by inhibiting bovine serum albumin denaturation. The extract induced a moderate concentration-dependent reduction in HeLa cell viability without cytotoxicity toward HaCaT cells. Comet assay results demonstrated DNA damage in HeLa cells at higher concentrations, while AHA significantly suppressed zymosan-induced IL-1β gene expression. These findings indicate that AHA is a promising natural source of bioactive compounds with diverse biological activities. Full article

The use of nanoscale materials has expanded rapidly in recent decades, with titanium dioxide (TiO₂) nanoparticles among the most widely produced. Their increasing environmental release raises concerns about ecosystem-level effects. A key mechanism of toxicity is the generation of reactive oxygen species (ROS), although these effects strongly depend on particle properties, including crystalline form, size, morphology, surface characteristics, and exposure conditions. Here, we assessed and compared the ecological impacts of anatase and rutile TiO₂ nanoparticles across prokaryotic and eukaryotic systems, including aquatic microbial communities, microbial cultures, plant bioassays (Sinapis alba, Triticum aestivum), the SOS Chromotest, and zebrafish (Danio rerio) assays. Nano-TiO₂ exposure markedly restructured freshwater microbial communities by suppressing sensitive taxa (e.g., Actinomycetota, Flavobacterium, and Limnohabitans) while enriching more tolerant genera such as Pseudomonas, Sediminibacterium, Haliscomenobacter, and Hydrogenophaga. These shifts likely reflect differences in cell-envelope structure, biofilm formation, and antioxidant capacity. The two investigated TiO₂ nanoparticle types showed distinct biological effects: rutile was associated with more pronounced microbial community shifts and bacterial cell damage, whereas anatase caused stronger responses in plant assays, particularly by impairing hypocotyl growth and plant water balance. Besides the limited acute genotoxicity revealed by the SOS Chromotest, TiO₂ nanoparticles did not significantly affect survival or final larval body length in the zebrafish embryo assay under the tested conditions; however, the hatching delay observed at the highest concentration indicated a sublethal developmental effect. Overall, our results show that TiO₂ nanoparticle toxicity cannot be generalized across biological systems and suggest that biological responses depend on the combined influence of particle characteristics and organism-specific structural and physiological traits. Full article

The toxicity of oxybenzone (benzophenone-3; BP-3), a UV filter present in coral reef waters at toxic concentrations, has been incompletely characterized for oxidative stress responses in adult cnidarians. In order to examine this, Aiptasia pallida (an anemone commonly used as a coral research model) was exposed to oxybenzone at concentrations of 0.02, 0.2, 2.0, and 3.0 mg/L for 5, 10, and 30 days (n = 4 tanks per treatment). Catalase (CAT) and superoxide dismutase (SOD) activity, glutathione levels, and the alkaline comet assay (% DNA in tail) were analyzed. CAT increased significantly at all concentrations and timepoints, with 80.6% maximum induction at 2.0 mg/L on Day 30 and a LOEC of 0.02 mg/L. SOD showed no significant response at any timepoint. The levels of glutathione increased at Day 5 for the two highest concentrations, but decreased at Day 10 for 3.0 mg/L. Genotoxic effects were significant at Days 5 and 10, with a threshold between 0.02 and 2.0 mg/L. A significant positive correlation between group mean CAT activity and % DNA in the tail contrasted with a null SOD–DNA association, identifying hydrogen peroxide, not superoxide, as the proximate genotoxic driver in adult cnidarian tissue. These results indicate that oxybenzone induces oxidative stress responses in A. pallida. Full article

The current study describes the synthesis and preliminary anticancer assessment of a novel series of C3/C28-bis-1,2,4-triazolyl-sulfanylacetate-betulin (AP1–5) derivatives to identify potent agents for clinical development. The cytotoxicity of AP1–5 was evaluated using the Alamar blue assay against MCF-7, A375, PANC-1 (cancer cells) and HaCat (human keratinocytes) cells. Moreover, the molecular mechanisms responsible for cytotoxicity were investigated through in vitro (DCFDA/H₂DCDFA assay, caspase-3/7 assay, and morphological analysis) and in silico assays (network pharmacology, molecular docking, molecular dynamics simulation, and ADMET predictions). The result highlighted AP5, containing unsubstituted 1,2,4-triazoles, as the lead derivative of the series with increased potency against MCF-7, with an IC₅₀ value of 7.41 μM compared to its phenyl-substituted analogs (AP1–4). The derivatives induced apoptosis, marked by fragmented nuclei, round cells, disorganized cytoskeletons, and activation of caspases-3/-7 through a ROS-decreasing mechanism. The network pharmacology assessment predicted AP5 may interact with key proteins in the PI3K/Akt pathway, such as MAP2K1, MDM2, IGF1, JAK2, IL2 and FGFR1, as well as ESR1, PGR and MMP2. Molecular docking suggested MMP-2 is the most favorable target for AP5 among the validated proteins, while molecular dynamics simulations supported the predicted AP5–MMP-2 interaction. Moreover, the ADMET profiling of AP5 showed acceptable intestinal absorption, non-glycoprotein-P substrate status, and reduced hepatic metabolism compared to betulin. However, the ADMET analysis also highlighted some potential toxicity risks such as DILI, genotoxicity, carcinogenicity and skin sensitization that need to be further investigated. Altogether, these promising findings support the further exploration of AP5 as a promising drug candidate for breast cancer in vivo to assess its potency and toxicity. Full article

N-nitrosamines and acrylamide are food mutagens classified as “probably carcinogenic to humans (Group 2A)” by the International Agency for Research on Cancer (IARC) from evidence of carcinogenicity. One of the main objectives of food safety is to reduce the presence of these substances in food. Therefore, the present study aimed to evaluate the effect of the addition of propolis, royal jelly or a combination of both bee products (2–10%) to chestnut and thyme honey on their protective properties against food mutagen-induced genotoxicity. DNA damage was evaluated by the alkaline comet assay. N-nitrosamines (N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR)) and acrylamide (AA) induced genotoxicity in human hepatoma HepG2 cells. All tested samples at all concentrations used (0.1–10 µg/mL) decreased genotoxic effects of the three food mutagens. The protective effects of honey samples and mixtures towards DNA damage induced by food mutagens were in the following order: NDMA > AA > NPYR, being more effective against NDMA compared to AA and NPYR. The mixtures of chestnut honey with 10% propolis, or 10% royal jelly, and 10% propolis showed a greater protective effect against NDMA, NPYR and AA compared to the honey sample alone. This protective activity may be attributable to the phenolic compound content and antioxidant capacity exhibited by the analyzed samples. Overall, the results suggest that thyme and chestnut honey supplemented with bee-derived products could represent potential natural chemopreventive candidates against food-borne mutagens. Full article

Background: Obesity is a chronic endocrine–metabolic disorder. The risk of comorbidities increases with a higher body mass index (BMI), particularly when BMI ≥ 35.0 kg/m². Common complications include insulin resistance, type 2 diabetes, dyslipidemia, and chronic low-grade inflammation, which collectively impair DNA stability by promoting the formation of genotoxic species. Methods: This non-randomised, quasi-experimental clinical intervention study included 53 participants (both sexes) with a BMI ≥ 35.0 kg/m², who were assigned to parallel experimental or control streams based on clinical needs and institutional eligibility. During a three-week intervention, the experimental group received a hospital-supervised very-low-calorie diet (VLCD; ~600 kcal/day) under continuous medical monitoring. Conversely, the control group followed a standard reduced-calorie diet (SRD) of 1500 kcal/day in a free-living home environment. Before and after the intervention, primary, oxidative, and permanent DNA damage were measured using alkaline, FPG-modified comet (peripheral blood mononuclear cells), and cytokinesis-block micronucleus cytome assays (phytohaemagglutinin-stimulated binucleated lymphocytes), alongside anthropometric and biochemical tracking. Results: Within-group evaluations revealed that both dietary regimens improved several metabolic health indicators, notably modulating insulin resistance, lipid profiles, and leukocyte counts. However, participants in the VLCD stream experienced significantly greater downward changes in body weight, BMI, and absolute lipid values. Crucially, the VLCD intervention was associated with a highly significant within-group reduction in parameters of permanent chromosomal damage, effectively halving the frequencies of micronuclei and nuclear buds, independent of baseline variations, in adjusted multivariate regression models. Conversely, the home-based SRD regimen demonstrated no measurable impact on permanent genomic damage. Neither diet induced a significant change in repairable primary or oxidative DNA lesions over this short timeframe. Conclusions: These exploratory findings suggest that strict calorie restriction can rapidly stabilise genome stability in advanced clinical settings, warranting future randomised controlled trials with long-term longitudinal follow-up to assess permanent risk reductions. Due to structural baseline variations in age, chronic comorbidities, and compliance environments between the cohorts, direct comparative superiority cannot be definitively established. Full article

Commercially available graphene quantum dots (GQDs) are promising nanomaterials for applications in research and preclinical diagnostics, drug delivery, and bioimaging. Their bioactivity is highly dependent on dose, route of exposure, duration, cell type, uptake mechanisms, tissue and cellular distribution, and physicochemical properties. This study aimed to evaluate genotoxic, cytotoxic, and cytostatic endpoints of blue- (B-GQDs) and green-emitting (G-GQDs) GQDs in human blood and salivary leukocytes. GQDs were tested at concentrations ranging from 2.5 to 100 µg/mL using distinct treatment periods. Fourier transform infrared spectroscopy (FTIR), trypan blue exclusion, comet, and cytokinesis-block micronucleus cytome (CBMN cyt) assays were performed. FTIR analysis revealed that G-GQDs, unlike B-GQDs, exhibit an absorption band typically associated with amine functional groups, which may contribute to their pronounced genotoxic effects. Peripheral blood mononuclear cells and salivary leukocytes showed higher sensitivity to G-GQDs compared to whole blood samples. Although no cytotoxic effects were observed, both GQDs induced significant DNA damage, with G-GQDs demonstrating greater genotoxic potential. These findings demonstrate that GQDs can induce DNA damage in the absence of detectable cytotoxic effects under the conditions tested, highlighting the importance of considering both physicochemical properties and cellular models in the safety assessment of nanomaterials. Full article

Aspergillus cristatus is a key microorganism involved in the fermentation of Fu brick tea, but systematic strain-level safety data remain limited despite its long history of use in dark tea production. In this study, the toxicological safety of A. cristatus CCNH008 was assessed through acute oral toxicity assay, a 90-day repeated oral toxicity study with a recovery period and genotoxicity assays. In acute oral toxicity tests, CCNH008 caused no mortality, no adverse clinical signs, and no treatment-related effects on bodyweight or pathology in mice or rats, with an LD₅₀ greater than 10 g/kg bodyweight. In the 90-day repeated oral toxicity study in rats, the oral administration of CCNH008 at doses up to 1.67 g/kg bodyweight/day produced no treatment-related changes in clinical signs, bodyweight, food consumption, hematological or biochemical parameters, urinalysis, organ weights, or histopathology, including during a 28-day recovery period. Genotoxicity was evaluated using a bacterial reverse mutation assay, an in vitro mammalian chromosome aberration test, and an in vivo mammalian erythrocyte micronucleus test; no mutagenic or clastogenic effects were observed. Collectively, these findings demonstrate that CCNH008 shows no evidence of acute, subchronic oral toxicity, or genotoxicity, providing important strain-level safety evidence to support its potential application in food-related products. Full article

The potential effects of microplastics (MPs) on humans and ecosystems are of great concern, and it has been reported that the ingestion of contaminated food is the main route of exposure. In the present study, Perca fluviatilis was selected as a vertebrate model to evaluate the possible cellular effects induced by five different plastic polymers and car tire debris (CT) after 4- and 7-month exposure periods. The Cytome assay was chosen to check chromatin alteration in perch’s peripheral blood. The results indicated an increase in micronuclei and cytotoxic effect in specimens co-exposed to MPs + CT for 7 months. Increases in dicentric chromosomes were observed in specimens exposed both to MPs alone and to the mixture of MPs + CT, indicating for the first time a genotoxic effect induced by CT debris in fish in terms of structural aberrations. Increases in micronucleated erythrocyte frequency assessed after 7 months only after the addition of CT debris to the mixture of MPs might suggest an aneugenic action of CT in fish. In the same groups, the higher values of frequency in 8-shaped erythrocytes also indicate possible cell cycle toxicity exerted by CT exposure. An association between total erythrocyte nuclear morphology abnormalities (ENA) and glutathione reductase activity was also found, indicating a potential involvement of oxidative processes in modulating the genotoxicity observed. The present experimental model is a useful tool to study cellular mechanisms related to both MP- and CT-induced chromatin structure alterations indicating possible interference with human health as well. Full article

Chronic inhalation exposure to nanoplastics, specifically polyethylene terephthalate (PET) nanoplastics (PET-NPLs) is an emerging health concern, yet the long-term consequences for genomic stability and DNA damage response (DDR) capacity in bronchial epithelial cells remain poorly characterized. For this study, human bronchial epithelial BEAS-2B cells were continuously exposed to PET-NPLs for over 20 weeks, after which elevated basal DNA genotoxic damage was observed, as assessed by the alkaline comet assay. In addition, a broad transcriptional suppression of the DDR, with 27 of 84 profiled genes involved in DDR showing reduced expression relative to passage-matched control was observed. The suppressed genes span ATM/ATR checkpoint signaling, homologous recombination (HR), base excision repair (BER), nucleotide excision repair (NER), and apoptotic pathways. To determine whether chronic PET-NPL exposure altered susceptibility to acute genotoxic challenge in a damage-type-specific manner, cells were treated with methyl methanesulfonate (MMS), ultraviolet-C (UV-C) radiation, or bleomycin. While MMS and UV-C induced comparable levels of DNA damage in control and PET-exposed cells, bleomycin produced significantly greater damage in PET-exposed cells, indicating selective sensitization to doble-strand breaks (DSB)-type and oxidative genotoxic insults. Transcriptional profiling during bleomycin challenge identified 18 DDR genes with relatively higher expression in PET-exposed cells compared to passage-matched controls, encompassing HR, BER, ATM/ATR signaling, the Fanconi anemia pathway, and apoptosis. Furthermore, PET-exposed cells retained significantly higher residual DNA damage after 3 h of bleomycin challenge, indicating a persistent early repair deficit. Together, these findings suggest that chronic PET-NPL exposure specifically compromises the bronchial epithelial DDR, with potential implications for long-term genomic stability in respiratory epithelia subjected to nanoplastic inhalation. Full article

Pesticide formulations may influence toxicological outcomes beyond the intrinsic properties of active ingredients; however, these differences are often overlooked in regulatory risk assessment. Using human liver HepG2 cells, this study compared the cytotoxic and genotoxic effects of two commercial lambda-cyhalothrin formulations that differ in formulation type and in composition: an emulsifiable concentrate (Lambda-Cyhalothrin 5% EC) and a suspension concentrate co-formulated with thiamethoxam (Duer SC). Cytotoxicity was assessed using propidium iodide exclusion, while genotoxicity was evaluated using the cytokinesis-block micronucleus (CBMN) and alkaline comet assays. Lambda-Cyhalothrin 5% EC showed significant cytotoxicity from 500 μM onward, whereas Duer SC induced cytotoxic effects even at lower concentrations beginning at 200 μM, indicating greater cytotoxic potency of the combined formulation. Lambda-Cyhalothrin 5% EC induced a concentration-dependent increase in the number of binucleated cells containing micronuclei, with a significant effect at 50 μM. Duer SC also increased micronucleus frequency but did not differ significantly from the negative control. Proliferation indices remained comparable to controls for both formulations. The comet assay showed that Lambda-Cyhalothrin 5% EC produced significant DNA damage from 10 μM onward, while Duer SC exhibited minimal genotoxic effects. These findings demonstrate that formulation type modifies the toxicological profile of lambda-cyhalothrin. Full article

Background: Nosocomial infections caused by multidrug-resistant microorganisms are a significant public health concern. Antimicrobial resistance (AMR) is closely linked to the excessive and indiscriminate use of antibiotics, which creates selective pressure and promotes the emergence of resistant pathogens. Objectives: This study evaluates the synergistic potential of intragenic antimicrobial peptides (IAPs) combined with plant alkaloids against susceptible and multidrug-resistant human pathogenic bacteria, assessing antimicrobial activity, biofilm inhibition, and hemocompatibility. Methods: The tested molecules included berberine, tomatidine, sinomenine, and the IAPs Hs02 and Gr01. Minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) assays were performed against both ATCC (E. coli ATCC 25922 and S. aureus ATCC 25923) and clinical strains (E. coli KPC+ HRAN 1812446 and S. aureus MDR LACEN 3730529). Synergistic interactions were evaluated by checkerboard assay, followed by biofilm inhibition and hemolysis assays using human red blood cells. Results: Berberine exhibited a MIC of 1024 µM when tested individually, while tomatidine and sinomenine showed no significant activity. As expected, the IAPs showed strong antimicrobial properties at 8 µM (Hs02) and 4 µM (Gr01). When tested in synergy, alkaloids and IAPs reduced the MIC by up to 128-fold. The combination of IAPs and alkaloids reduced the biofilm biomass of S. aureus and E. coli by 50%, by the crystal violet assay (p < 0.05). Notably, sinomenine had not previously been reported to have antimicrobial activity. Conclusions: These results highlight the importance of further exploring combinations of natural and synthetic bioactive molecules as promising antimicrobial candidates. This approach may help to extend the useful life of conventional antibiotics. However, further studies are needed to assess safety, cytotoxicity, genotoxicity, inflammation, and in vivo effects. Full article

This study evaluates the cytotoxic and genotoxic-like potential of an ipfencarbazone-based herbicide formulation (IPF-BH; commercial product Hokuto, containing 250 g/L of the triazolinone herbicide ipfencarbazone) in human peripheral lymphocytes in vitro across a concentration range of 62.5–1000 µg/mL. Cytotoxicity was monitored via the mitotic index (MI), while cytogenetic damage was assessed using the cytokinesis-block micronucleus (MN) assay and the alkaline comet assays. Comparisons were performed using one-way ANOVA, followed by Dunnett’s post hoc test, against the negative control. Results indicated a concentration-dependent cytotoxic effect, with a marked reduction in MI observed at all tested concentrations (p < 0.001). MN frequency was significantly elevated at concentrations ≥125 µg/mL, whereas the 62.5 µg/mL concentration did not induce significant micronuclei formation. The comet assay revealed increased DNA damage parameters (tail length, tail intensity (%), and tail moment) across the tested concentration range, albeit with a non-monotonic profile for tail length and tail intensity. These findings suggest that IPF-BH exposure is associated with marked cytotoxicity and a genotoxic response in this in vitro model at concentrations within the OECD 487-acceptable cytotoxicity window, together with cytotoxicity-associated genotoxic-like effects at strongly cytotoxic concentrations in human peripheral lymphocytes under in vitro conditions. Because IPF-BH is a commercial formulation, and no direct mechanistic endpoints (e.g., reactive oxygen species, mitochondrial transmembrane potential, lipid peroxidation, glutathione) were measured, and because the present design was performed without exogenous metabolic activation (no S9 supplementation), the observed effects cannot be unambiguously attributed to ipfencarbazone alone or to a defined mechanism of action; extrapolation to in vivo genotoxicity requires complementary +S9 and rodent in vivo follow-up studies. Full article