1. Nano spray-dried particles of in-situ crosslinked alginate and their toxicological characterisationJaka Levanič, Ilja Gasan Osojnik Črnivec, Iza Rozman, Mihaela Skrt, Alja Štern, Bojana Žegura, Nataša Poklar Ulrih, 2024, izvirni znanstveni članek Povzetek: The feasibility and technical capacity for producing crosslinked sub-micron gels with a nano spray-dryer were studied with variable pH systems incorporating alginate, pectin, and pullulan. The obtained powders were characterized for their morphology, particle size distribution, and their toxicological safety profile using genotoxicity and cytotoxicity assays. Additionally, quercetin was added to the encapsulation system to study the potential of the system to encapsulate this material. The produced powders exhibited morphologies and particle size distributions characteristic for nano spray-drying. The addition of pullulan and pectin to the feed solutions resulted in a particle size increase, with crosslinked alginate particles having a mean value of 1.43 μm, while particles with added pectin and pullulan had a mean particle size of 1.70 and 1.75 μm, respectively. The inclusion of quercetin proved to be problematic with this encapsulation system. Extremely high degradation rates and extremely low encapsulation efficiencies were observed due to the alkaline pH (~10) of the system that is needed to keep the feed dispersion in a liquid state and prevent premature crosslinking of the alginate. Although pectin and pullulan provided some protection for quercetin in the alkaline dispersion, the absolute quercetin content in the final product remained very low, with a maximum achieved encapsulation efficiency of 2.06 %. The safety profile of most produced powders was favourable, as they did not exhibit any significant cytotoxic and genotoxic activity in the HepG2 cell line, except in the case of Alginate/Pullulan which showed a 43 % decrease in cell viability at 500 μg/mL. Samples where quercetin was added did not show any increased toxicological effect.
Ključne besede: alginate, polysaccharides, crosslinking, nano spray drying, toxicological evaluation
Objavljeno v DiRROS: 08.05.2025; Ogledov: 115; Prenosov: 72
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2. Hazard characterization of the mycotoxins enniatins and beauvericin to identify data gaps and improve risk assessment for human healthAnne-Cathrin Behr, Christiane Kruse Fæste, Amaya Azqueta, Ana P. M. Tavares, Anastasia Spyropoulou, Anita Solhaug, Ann-Karin Olsen, Ariane Vettorazzi, Bojana Žegura, Matjaž Novak, 2025, pregledni znanstveni članek Povzetek: Enniatins (ENNs) and beauvericin (BEA) are cyclic hexadepsipeptide fungal metabolites which have demonstrated antibiotic, antimycotic, and insecticidal activities. The substantial toxic potentials of these mycotoxins are associated with their ionophoric molecular properties and relatively high lipophilicities. ENNs occur extensively in grain and grain-derived products and are considered a food safety issue by the European Food Safety Authority (EFSA). The tolerable daily intake and maximum levels for ENNs in humans and animals remain unestablished due to key toxicological and toxicokinetic data gaps, preventing full risk assessment. Aiming to find critical data gaps impeding hazard characterization and risk evaluation, this review presents a comprehensive summary of the existing information from in vitro and in vivo studies on toxicokinetic characteristics and cytotoxic, genotoxic, immunotoxic, endocrine, reproductive and developmental effects of the most prevalent ENN analogues (ENN A, A1, B, B1) and BEA. The missing information identified showed that additional studies on ENNs and BEA have to be performed before sufficient data for an in-depth hazard characterisation of these mycotoxins become available.
Ključne besede: enniatins, beauvericin, genotoxicity, endocrine effects, immunotoxicology, toxicokinetics
Objavljeno v DiRROS: 14.04.2025; Ogledov: 146; Prenosov: 61
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3. Muscle gene electrotransfer is increased by the antioxidant tempol in miceBoštjan Markelc, Gregor Tevž, Maja Čemažar, Simona Kranjc Brezar, Jaka Lavrenčak, Bojana Žegura, Justin Teissié, Gregor Serša, 2012, izvirni znanstveni članek Povzetek: Electropermeabilization (EP) is an effective method of gene transfer into different tissues. During EP, reactive oxygen species (ROS) are formed, which could affect transfection efficiency. The role of generated ROS and the role of antioxidants in electrotransfer in myoblasts in vitro and in Musculus tibialis cranialis in mice were, therefore, investigated. We demonstrate in the study that during EP of C2C12 myoblasts, ROS are generated on the surface of the cells, which do not induce long-term genomic DNA damage. Plasmid DNA for transfection (pEGFP-N1), which is present outside the cells during EP, neutralizes the generated ROS. The ROS generation is proportional to the amplitude of the electric pulses and can be scavenged by antioxidants, such as vitamin C or tempol. When antioxidants were used during gene electrotransfer, the transfection efficiency of C2C12 myoblasts was statistically significantly increased 1.6-fold with tempol. Also in vivo, the transfection efficiency of M. tibialis cranialis in mice was statistically significantly increased 1.4-fold by tempol. The study indicates that ROS are generated on cells during EP and can be scavenged by antioxidants. Specifically, tempol can be used to improve gene electrotransfer into the muscle and possibly also to other tissues.
Ključne besede: electropermeabilization, gene electrotransfer, muscle, tempol, reactive oxygen species
Objavljeno v DiRROS: 26.02.2025; Ogledov: 234; Prenosov: 117
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4. Cold plasma within a stable supercavitation bubble - a breakthrough technology for efficient inactivation of viruses in waterArijana Filipić, David Dobnik, Ion Gutiérrez-Aguirre, Maja Ravnikar, Tamara Košir, Špela Baebler, Alja Štern, Bojana Žegura, Martin Petkovšek, Matevž Dular, Miran Mozetič, Rok Zaplotnik, Gregor Primc, 2023, izvirni znanstveni članek Povzetek: Water scarcity, one of the most pressing challenges we face today, has developed for many reasons, including the increasing number of waterborne pollutants that affect the safety of the water environment. Waterborne human, animal and plant viruses represent huge health, environmental, and financial burden and thus it is important to efficiently inactivate them. Therefore, the main objective of this study was to construct a unique device combining plasma with supercavitation and to evaluate its efficiency for water decontamination with the emphasis on inactivation of viruses. High inactivation (>5 log10 PFU/mL) of bacteriophage MS2, a human enteric virus surrogate, was achieved after treatment of 0.43 L of recirculating water for up to 4 min. The key factors in the inactivation were short-lived reactive plasma species that damaged viral RNA. Water treated with plasma for a short time required for successful virus inactivation did not cause cytotoxic effects in the in vitro HepG2 cell model system or adverse effects on potato plant physiology. Therefore, the combined plasma-supercavitation device represents an environmentally-friendly technology that could provide contamination-free and safe water.
Ključne besede: cold plasma, hydrodynamic cavitation, supercavitation, virus inactivation, water decontamination, toxicity assays
Objavljeno v DiRROS: 28.11.2024; Ogledov: 336; Prenosov: 561
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5. In vitro hepatic 3D cell models and their application in genetic toxicology : a systematic reviewMartina Štampar, Bojana Žegura, 2024, pregledni znanstveni članek Povzetek: The rapid development of new chemicals and consumer products has raised concerns about their potential genotoxic effects on human health, including DNA damage leading to serious diseases. For such new chemicals and pharmaceutical products, international regulations require genotoxicity data, initially obtained through in vitro tests, followed by in vivo experiments, if needed. Traditionally, laboratory animals have been used for this purpose, however, they are costly, ethically problematic, and often unreliable due to species differences. Therefore, innovative more accurate in vitro testing approaches are rapidly being developed to replace, refine and reduce (3R) the use of animals for experimental purposes and to improve the relevance for humans in toxicology studies. One of such innovative approaches are in vitro three-dimensional (3D) cell models, which are already being highlighted as superior alternatives to the two-dimensional (2D) cell cultures that are traditionally used as in vitro models for the safety testing of chemicals and pharmaceuticals. 3D cell models provide physiologically relevant information and more predictive data for in vivo conditions. In the review article, we provide a comprehensive overview of 3D hepatic cell models, including HepG2, HepG2/C3A, HepaRG, human primary hepatocytes, and iPSC-derived hepatocytes, and their application in the field of genotoxicology. Through a detailed literature analysis, we identified 31 studies conducted between 2007 and April 2024 that used a variety of standard methods, such as the comet assay, the micronucleus assay, and the γH2AX assay, as well as new methodological approaches, including toxicogenomics, to assess the cytotoxic and genotoxic activity of chemicals, nanoparticles and natural toxins. Based on our search, we can conclude that the use of in vitro 3D cell models for genotoxicity testing has been increasing over the years and that 3D cell models have an even greater potential for future implementation and further refinement in genetic toxicology and risk assessment.
Ključne besede: genotoxicity, advanced 3D in vitro models, hepatic cells, spheroids, comet assay, micronucleus assay, genotoxicology, toxicological studies
Objavljeno v DiRROS: 14.11.2024; Ogledov: 504; Prenosov: 207
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6. Impact of indoor air pollution on DNA damage and chromosome stability : a systematic reviewLuka Kazensky, Katarina Matković, Marko Gerić, Bojana Žegura, Gordana Pehnec, Goran Gajski, 2024, pregledni znanstveni članek Povzetek: Indoor air pollution is becoming a rising public health problem and is largely resulting from the burning of solid fuels and heating in households. Burning these fuels produces harmful compounds, such as particulate matter regarded as a major health risk, particularly affecting the onset and exacerbation of respiratory diseases. As exposure to polluted indoor air can cause DNA damage including DNA sd breaks as well as chromosomal damage, in this paper, we aim to provide an overview of the impact of indoor air pollution on DNA damage and genome stability by reviewing the scientific papers that have used the comet, micronucleus, and γ-H2AX assays. These methods are valuable tools in human biomonitoring and for studying the mechanisms of action of various pollutants, and are readily used for the assessment of primary DNA damage and genome instability induced by air pollutants by measuring different aspects of DNA and chromosomal damage. Based on our search, in selected studies (in vitro, animal models, and human biomonitoring), we found generally higher levels of DNA strand breaks and chromosomal damage due to indoor air pollutants compared to matched control or unexposed groups. In summary, our systematic review reveals the importance of the comet, micronucleus, and γ-H2AX assays as sensitive tools for the evaluation of DNA and genome damaging potential of different indoor air pollutants. Additionally, research in this particular direction is warranted since little is still known about the level of indoor air pollution in households or public buildings and its impact on genetic material. Future studies should focus on research investigating the possible impact of indoor air pollutants in complex mixtures on the genome and relate pollutants to possible health outcomes.
Ključne besede: indoor air quality, genome damage, comet assay, micronucleus assay, γ-H2AX assay, health risk
Objavljeno v DiRROS: 06.11.2024; Ogledov: 399; Prenosov: 195
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7. Evidence driven indoor air quality improvement : an innovative and interdisciplinary approach to improving indoor air qualityMario Lovrić, Goran Gajski, Jessica Fernández-Agüera, Mira Pöhlker, Bojana Žegura, Matjaž Novak, Alja Štern, Katja Kološa, Martina Štampar, 2024, pregledni znanstveni članek Povzetek: Indoor air pollution is a recognized emerging threat, claiming millions of lives annually. People are constantly exposed to ambient and indoor air pollution. The latest research shows that people in developed countries spend up to 90% of their time indoors and almost 70% at home. Although impaired IAQ represents a significant health risk, it affects people differently, and specific populations are more vulnerable: children, the elderly, and people with respiratory illnesses are more sensitive to these environmental risks. Despite rather extensive research on IAQ, most of the current understanding about the subject, which includes pollution sources, indoor–outdoor relationships, and ventilation/filtration, is still quite limited, mainly because air quality monitoring in the EU is primarily focused on ambient air quality and regulatory requirements are lacking for indoor environments. Therefore, the EDIAQI project aims to improve guidelines and awareness for advancing the IAQ in Europe and beyond by allowing user-friendly access to information about indoor air pollution exposures, sources, and related risk factors. The solution proposed with EDIAQI consists of conducting a characterization of sources and routes of exposure and dispersion of chemical, biological, and emerging indoor air pollution in multiple cities in the EU. The project will deploy cost-effective/user-friendly monitoring solutions to create new knowledge on sources, exposure routes, and indoor multipollutant body burdens. The EDIAQI project brings together 18 organizations from 11 different European countries that provide interdisciplinary skills and expertise in various fields, including environmental science and technology, medicine, and toxicology, as well as policy design and public engagement.
Ključne besede: indoor air pollution, health risk, vulnerable populations, IAQ (Indoor Air Quality), EDIAQI project, monitoring solutions, exposure routes
Objavljeno v DiRROS: 06.11.2024; Ogledov: 404; Prenosov: 1336
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8. Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human healthHenriqueta Louro, Ariane Vettorazzi, Adela López de Cerain, Bojana Žegura, Matjaž Novak, 2024, pregledni znanstveni članek Povzetek: Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers.
Ključne besede: mycotoxin, exposure routes, genotoxicity, endocrine disruption, immunosuppression, biotransformation, toxicokinetics, tenuazonic acid, alternariol, altenuene, tentoxin, altertoxin
Objavljeno v DiRROS: 07.08.2024; Ogledov: 501; Prenosov: 354
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9. Synthesis, purification, and cell-toxicity of a choline betainateLucija Jurko, Gregor Hostnik, Tobias Alexander Steindorfer, Alja Štern, Perica Bošković, Matej Bračič, Bojana Žegura, Rupert Kargl, 2024, izvirni znanstveni članek Povzetek: In this work, choline chloride and betaine hydrochloride were condensed into a - to our knowledge - unreported choline betainate (N,N,N-trimethyl-2-oxo-2-(2-(trimethylammonio)ethoxy)ethanaminium chloride) using 1,1′-carbonyldiimidazole (CDI) activation of betaine hydrochloride in dimethylsulfoxide. The product and reaction intermediates were isolated, purified by preparative HPLC and analyzed in detail by infrared and nuclear magnetic resonance spectroscopy. The final product has a high cytotoxicity for L929 mouse fibroblasts, and low antibacterial activity against P. Aeruginosa and S. Aureus at concentrations of up to 20 mg/ml. It could potentially further be investigated for similar uses as suxamethonium chloride, a muscle relaxant drug.
Ključne besede: choline chloride, betaine hydrochloride, carbonyldiimidazole, HPLC, antimicrobial, cytotoxicity
Objavljeno v DiRROS: 07.08.2024; Ogledov: 559; Prenosov: 459
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10. New approach methodologies to facilitate and improve the hazard assessment of non-genotoxic carcinogens : a PARC projectMarc Audebert, Ann-Sophie Assmann, Amaya Azqueta, Pavel Babica, Emilio Benfenati, Martina Štampar, Bojana Žegura, 2023, pregledni znanstveni članek Povzetek: Carcinogenic chemicals, or their metabolites, can be classified as genotoxic or non-genotoxic carcinogens (NGTxCs). Genotoxic compounds induce DNA damage, which can be detected by an established in vitro and in vivo battery of genotoxicity assays. For NGTxCs, DNA is not the primary target, and the possible modes of action (MoA) of NGTxCs are much more diverse than those of genotoxic compounds, and there is no specific in vitro assay for detecting NGTxCs. Therefore, the evaluation of the carcinogenic potential is still dependent on long-term studies in rodents. This 2-year bioassay, mainly applied for testing agrochemicals and pharmaceuticals, is time-consuming, costly and requires very high numbers of animals. More importantly, its relevance for human risk assessment is questionable due to the limited predictivity for human cancer risk, especially with regard to NGTxCs. Thus, there is an urgent need for a transition to new approach methodologies (NAMs), integrating human-relevant in vitro assays and in silico tools that better exploit the current knowledge of the multiple processes involved in carcinogenesis into a modern safety assessment toolbox. Here, we describe an integrative project that aims to use a variety of novel approaches to detect the carcinogenic potential of NGTxCs based on different mechanisms and pathways involved in carcinogenesis. The aim of this project is to contribute suitable assays for the safety assessment toolbox for an efficient and improved, internationally recognized hazard assessment of NGTxCs, and ultimately to contribute to reliable mechanism-based next-generation risk assessment for chemical carcinogens.
Ključne besede: non-genotoxic carcinogens, NGTxC, new approach methodologies, NAM, PARC
Objavljeno v DiRROS: 05.08.2024; Ogledov: 484; Prenosov: 262
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