During almost 40 years of use, the micronucleus assay (MN) has become one of the most popular methods to assess genotoxicity of different chemical and physical factors, including ionizing ...radiation-induced DNA damage. In this minireview, we focus on the position of MN among the other genotoxicity tests, its usefulness in different applications and visibility by international organizations, such as International Atomic Energy Agency, Organization for Economic Co-operation and Development and International Organization for Standardization. In addition, the mechanism of micronuclei formation is discussed. Finally, foreseen directions of the MN development are pointed, such as automation, buccal cells MN and chromothripsis phenomenon.
The Vanilla genus is crucial for global production in food, perfume, and pharmaceutical industries. However, exploitation threatens some species, leading to extinction. Traditional communities use ...vanilla for medicinal purposes, and there are species like Vanilla chamissonis Klotzsch and Vanilla bahiana Hoehne with potential to occupy the market. For this, methanolic extraction of these two mentioned species was conducted alongside Vanilla planifolia. Analyzes of the cell viability, mutagenic and genotoxic potential were performed. In the Ames test, the assays were performed with concentrations from 0.5 and 5000 μg/ml and on five strains. Only Vanilla planifolia exhibited mutagenicity at the highest concentration in the TA98 strain. Viability tests were performed within a dose range of 0.05–5000 µg/ml and 24, 48, and 72-hour exposures. It was possible to observe a reduction in cell viability observed only at the highest concentration, for all three species and both cell types tested. Genotoxicity induction by the extracts was assessed at concentrations from 0.5 to 500 µg/ml through the cytokinesis-block micronucleus assay. No genotoxic damage or reduction in the Nucleus Division Index (NDI). The study found no mutagenicity, cytotoxicity, or genotoxicity in the species tested, indicating potential human use for food or pharmaceutical purposes.
Display omitted
•Brazilian Vanilla species extracts show no mutagenicity or genotoxicity.•Only V. planifolia exhibited mutagenicity at the highest concentration.•Cell viability reduced only at the highest extract concentrations in all species.•Vanilla extracts show potential for safe use in food and pharmaceutical industries.•None of the species induced micronuclei.
Schinus terebinthifolia Raddi (Anacardiaceae), known as Brazilian pepper tree, stands out as a medicinal plant widely used in traditional medicine. The leaves are popularly used as anti-inflammatory ...agent and to relieve inflammatory conditions such as bronchitis, ulcers, and wounds, for example.
The present study evaluated the acute toxicity, genotoxicity, and anti-inflammatory activity of S. terebinthifolia leaf lectin (SteLL) in mice (Mus musculus).
In the acute toxicity assay, the animals were treated intraperitoneally (i.p.) or orally (per os) with a single dose of 100 mg/kg. Genotoxicity was assessed by the comet and micronucleus assays. Carrageenan-induced peritonitis and paw edema models were used to evaluate the anti-inflammatory effects of SteLL (1, 5 and 10 mg/kg, i.p.).
No animal died and no signs of intoxication or histopathological damage were observed in the acute toxicity assay. Genotoxic effect was not detected. In peritonitis assay, SteLL reduced in 56–69% leukocyte migration to the peritoneal cavity; neutrophil count decreased by 25–32%, while mononuclear cell count increased by 67–74%. SteLL promoted a notable reduction of paw edema after 4 h (61.1–63.4%). Morphometric analysis showed that SteLL also decreased the thickness of epidermal edema (30.2–40.7%). Furthermore, SteLL decreased MPO activity, plasma leakage, NO release, and modulated cytokines in both peritoneal fluid and paw homogenate.
SteLL did not induce acute toxicity or genotoxicity in mice and stands out as a promising candidate in the development of new phytopharmaceuticals with anti-inflammatory action.
Display omitted
Primary concept of nickel toxicity – an overview Das, Kusal K.; Reddy, R. Chandramouli; Bagoji, Ishwar B. ...
Journal of basic and clinical physiology and pharmacology,
09/2018, Letnik:
30, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Toxic metals, including excessive levels of essential metals tend to change biological structures and systems into either reversible or irreversible conformations, leading to the derangement of organ ...functions or ultimate death. Nickel, a known heavy metal is found at very low levels in the environment. Nickel is available in all soil types and meteorites and also erupts from volcanic emissions. In the environment, nickel is principally bound with oxygen or sulfur and forms oxides or sulfides in earth crust. The vast industrial use of nickel during its production, recycling and disposal has led to widespread environmental pollution. Nickel is discharged into the atmosphere either by nickel mining or by various industrial processes, such as power plants or incinerators, rubber and plastic industries, nickel-cadmium battery industries and electroplating industries. The extensive use of nickel in various industries or its occupational exposure is definitely a matter of serious impact on human health. Heavy metals like nickel can produce free radicals from diatomic molecule through the double step process and generate superoxide anion. Further, these superoxide anions come together with protons and facilitate dismutation to form hydrogen peroxide, which is the most important reason behind the nickel-induced pathophysiological changes in living systems. In this review, we address the acute, subchronic and chronic nickel toxicities in both human and experimental animals. We have also discussed nickel-induced genotoxicity, carcinogenicity, immunotoxicity and toxicity in various other metabolically active tissues. This review specifically highlighted nickel-induced oxidative stress and possible cell signaling mechanisms as well.
•C60 fullerene can induce DNA damage.•C60 fullerene does not affect the reproductive system and embryogenesis.•Activation of DNA-repair might decrease the effects of C60 fullerene at the organismal ...level.
Fullerenes have attracted attention since their discovery as structural units of complex carbon nanostructures capable of transporting drugs and macromolecules. As such artificial nanomaterials are applied in biology and medicine, they are routinely scrutinized for their effects on living organisms. The results of such studies range from direct destabilizing effects on DNA molecules to amelioration of the toxic effects of known genotoxic agents. We tested the effect of buckminsterfullerene (C60) on Drosophila melanogaster at DNA, tissue and organism levels. The water-soluble pristine C60 fullerene at the concentration of 20 μg/ml and 40 μg/ml leads to the activation of the mus209 gene in D. melanogaster larvae salivary glands, which can indicate higher levels of DNA damage. However, the absence of effects at the cell and organismal level could be explained by the activation of repair systems or by active elimination of damaged cells.
Understanding the mode-of-action (MOA) of genotoxic compounds and differentiating between direct DNA interaction and indirect genotoxicity is crucial for their reliable safety assessment. ToxTracker ...is a stem cell-based reporter assay that detects activation of various cellular responses that are associated with genotoxicity and cancer. ToxTracker consists of 6 different GFP reporter cell lines that can detect the induction of DNA damage, oxidative stress, and protein damage in a single test. The assay can thereby provide insight into the MOA of compounds. Genotoxicity is detected in ToxTracker by activation of 2 independent GFP reporters. Activation of the Bscl2-GFP reporter is associated with induction of DNA adducts and subsequent inhibition of DNA replication and the Rtkn-GFP reporter is activated following the formation of DNA double-strand breaks. Here, we show that the differential activation of these 2 genotoxicity reporters could be used to further differentiate between a DNA reactive and clastogenic or a non-DNA-reactive aneugenic MOA of genotoxic compounds. For further classification of aneugenic and clastogenic compounds, the ToxTracker assay was extended with cell cycle analysis and aneuploidy assessment. The extension was validated using a selection of 16 (genotoxic) compounds with a well-established MOA. Furthermore, indirect genotoxicity related to the production of reactive oxygen species was investigated using the DNA damage and oxidative stress ToxTracker reporters in combination with different reactive oxygen species scavengers. With these new extensions, ToxTracker was able to accurately classify compounds as genotoxic or nongenotoxic and could discriminate between DNA-reactive compounds, aneugens, and indirect genotoxicity caused by oxidative stress.
The widespread use of nanomaterials in agriculture may introduce multiple engineered nanoparticles (ENPs) into the environment, posing a combined risk to crops. However, the precise molecular ...mechanisms explaining how plant tissues respond to mixtures of individual ENPs remain unclear, despite indications that their combined toxicity differs from the summed toxicity of the individual ENPs. Here, we used a variety of methods including physicochemical, biochemical, and transcriptional analyses to examine the combined effects of graphene nanoplatelets (GNPs) and titanium dioxide nanoparticles (TiO2 NPs) on hydroponically exposed lettuce (Lactuca sativa) seedlings. Results indicated that the presence of GNPs facilitated the accumulation of Ti as TiO2 NPs in the seedling roots. Combined exposure to GNPs and TiO2 NPs caused less severe oxidative damage in the roots compared to individual exposures. Yet, GNPs and TiO2 NPs alone and in combination did not cause oxidative damage in the shoots. RNA sequencing data showed that the mixture of GNPs and TiO2 NPs led to a higher number of differentially expressed genes (DEGs) in the seedlings compared to exposure to the individual ENPs. Moreover, the majority of the DEGs encoding superoxide dismutase displayed heightened expression levels in the seedlings exposed to the combination of GNPs and TiO2 NPs. The level of gene ontology (GO) enrichment in the seedlings exposed to the mixture of GNPs and TiO2 NPs was found to be greater than the level of GO enrichment observed after exposure to isolated GNPs or TiO2 NPs. Furthermore, the signaling pathways, specifically the “MAPK signaling pathway-plant” and “phenylpropanoid biosynthesis,” exhibited a close association with oxidative stress. This study has provided valuable insights into the molecular mechanisms underlying plant resistance against multiple ENPs.
Display omitted
•GNPs facilitated the accumulation of Ti as TiO2 NPs in the roots of lettuce seedlings.•Mixtures of GNPs and TiO2 NPs caused less severe oxidative damage to seedling.•GNPs and TiO2 NPs in mixture increased the amount of differentially expressed genes.•MAPK signaling pathway/phenylpropanoid biosynthesis contributed most to oxidative stress.•Seedling roots were more responsive to the combination of GNPs and TiO2 NPs than the shoots.
Engineered nanomaterials (ENMs) refer to a relatively novel class of materials that are increasingly prevalent in various consumer products and industrial applications – most notably for their ...superlative physicochemical properties when compared with conventional materials. However, consumer products inevitably degrade over the course of their lifetime, releasing ENMs into the environment. These ENMs undergo physicochemical transformations and subsequently accumulate in the environment, possibly leading to various toxic effects. As a result, a significant number of studies have focused on identifying the possible transformations and environmental risks of ENMs, with the objective of ensuring a safe and responsible application of ENMs in consumer products. This review aims to consolidate the results from previous studies related to each stage of the pathway of ENMs from being embodied in a product to disintegration/transformation in the environment. The scope of this work was defined to include the five most prevalent ENMs based on recent projected production market data, namely: nTiO2, nSiO2, nZnO, carbon nanotubes, and nAg. The review focuses on: (i) models developed to estimate environmental concentrations of ENMs; (ii) the possible physicochemical transformations; (iii) cytotoxicity and genotoxicity effects specific to each ENM selected; and (iv) a discussion to identify potential gaps in the studies conducted and recommend areas where further investigation is warranted.
Display omitted
•Transformations and toxicity of five most prevalent nanomaterials are discussed.•Aggregation, surface charge change and dissolution are the transformations observed.•Oxidative stress and ROS generation leads to cytotoxicity and genotoxicity.•DNA breakage, chromosomal aberration & micronuclei are notable genotoxic effects.•The research gaps are summarised and possible research directions are recommended.
Even though microplastics (MPs) and graphene nanomaterials (GNMs) have demonstrated individual toxicity towards aquatic organisms, the knowledge gap lies in the lack of understanding regarding their ...combined toxicity. The difference between the combined toxicity of MPs and GNMs, in contrast to their individual toxicities, and furthermore, the elucidation of the mechanism of this combined toxicity are scientific questions that remain to be addressed. In this study, we examined the individual and combined toxicity of three polystyrene microplastics (MPs) with different functional groups—unmodified, carboxyl-modified (COOH-), and amino-modified (NH2-) MPs—in combination with reduced graphene oxide (RGO) on the freshwater microalga Scenedesmus obliquus. More importantly, we explored the cellular and molecular mechanisms responsible for the observed toxicity. The results indicated that the growth inhibition toxicity of RGO, either alone or in combination with the three MPs, against S. obliquus increased gradually with higher particle concentrations. The mitigating effect of MPs-NH2 on RGO-induced toxicity was most significant at a higher concentration, surpassing the effect of unmodified MPs. However, the MPs-COOH did not exhibit a substantial impact on the toxicity of RGO. Unmodified MPs and MPs-COOH aggravated the inhibition effects of RGO on the cell membrane integrity and oxidative stress-related biomarkers. Additionally, MPs-COOH exhibited a stronger inhibition effect on RGO-induced biomarkers compared to unmodified MPs. In contrast, the MPs-NH2 alleviated the inhibition effect of RGO on the biomarkers. Furthermore, the presence of differently functionalized MPs did not significantly affect RGO-induced oxidative stress and photosynthesis-related gene expression in S. obliquus, indicating a limited ability to modulate RGO genotoxicity at the molecular level. These findings can offer a more accurate understanding of the combined risks posed by these micro- and nano-materials and assist in designing more effective mitigation strategies.
Display omitted
•Unmodified and amino-modified polystyrene MPs reduced toxicity of RGO to S. obliquus.•Carboxyl-modified polystyrene MPs did not affect the toxicity of RGO to S. obliquus.•Amino-modified polystyrene MPs alleviated inhibition effect of RGO on biomarkers.•Unmodified and carboxyl-modified MPs aggravated inhibition effects of RGO on biomarkers.•Differently functionalized polystyrene MPs did not affect RGO-induced gene expression.
PDF
