Evaluation of the Toxicity of Bisphenol A in Reproduction and Its Effect on Fertility and Embryonic Development in the Zebrafish (Danio rerio)

Bisphenol A (BPA) is a chemical substance commonly used in the manufacture of plastic products. Its inhalation or ingestion from particles in suspension, water, and/or polluted foods can trigger toxic effects related to endocrine disruption, resulting in hormonal, reproduction, and immunological alterations in humans and animals. The zebrafish (Danio rerio) is an ideal experimental model frequently used in toxicity studies. In order to assess the toxic effects of BPA on reproduction and embryonic development in one generation after parental exposure to it, a total of 80 zebrafish, males and females, divided into four groups in duplicate (n = 20) were exposed to BPA concentrations of 500, 50, and 5 µg L−1, along with a control group. The fish were kept in reproduction aquariums for 21 days. The embryos obtained in the crosses were incubated in a BPA-free medium and observed for signs of embryotoxicity. A histopathological study (under optical and electron microscopes) was performed of adult fish gonads. The embryos of reproducers exposed to BPA were those most frequently presenting signs of embryotoxicity, such as mortality and cardiac and musculoskeletal malformations. In the histopathological studies of adult individuals, alterations were found in ovocyte maturation and in spermatazoid formation in the groups exposed to the chemical. Those alterations were directly related to BPA action, affecting fertility in both sexes, as well as the viability of their offspring, proportionally to the BPA levels to which they were exposed, so that our results provide more information by associating toxic effects on the offspring and on the next generation.

Cell Adaptations of Rhodococci to Pharmaceutical Pollutants

Against the background of atense environmental situation, the risk of drug pollution in the natural environment is steadily increasing. Pharmaceuticals entering open ecosystems can cause toxic effects in wildlife from molecular to population levels. The aim of this research was to examine the impact of pharmaceutical pollutants on rhodococci, which are typical representatives of soil actinobacteria and active biodegraders of these compounds. The pharmaceutical products used in this research werediclofenac sodium and ibuprofen, which are non-steroidal anti-inflammatory drugs (NSAIDs) that are widely used and frequently found in the environment. The most common cell adaptations of rhodococci to the effects of NSAIDs were changes in zeta potential, catalase activity, morphometric parameters and degree of hydrophobicity; elevated contents of total cellular lipids; and the formation of cell conglomerates. The findings demonstrated the adaptation mechanisms of rhodococci and their increased resistance to the toxic effects of the pharmaceutical pollutants. Keywords: pharmaceutical pollutants, NSAIDs, diclofenac, ibuprofen, cell responses, Rhodococcus

Influence of Functional Group Modification on the Toxicity of Nanoplastics

Nanoplastics (NPs) are ubiquitous in harvested organisms at various trophic levels, and more concerns on their diverse responses and wide species-dependent sensitivity are continuously increasing. However, systematic study on the toxic effects of NPs with different functional group modifications is still limited. In this review, we gathered and analyzed the toxic effects of NPs with different functional groups on microorganisms, plants, animals, and mammalian/human cells in vitro. The corresponding toxic mechanisms were also described. In general, most up-to-date relevant studies focus on amino (−NH2) or carboxyl (−COOH)-modified polystyrene (PS) NPs, while research on other materials and functional groups is lacking. Positively charged PS-NH2 NPs induced stronger toxicity than negatively charged PS-COOH. Plausible toxicity mechanisms mainly include membrane interaction and disruption, reactive oxygen species generation, and protein corona and eco-corona formations, and they were influenced by surface charges of NPs. The effects of NPs in the long-term exposure and in the real environment world also warrant further study.

Influence of lead acetate on seed germination and growth of young alfalfa plants

This study presents the results of testing the effect of different concentrations of lead-acetate on seed germination and young Seedlings of alfalfa. Тhe experiment was organized so that in the first variant, only lead-acetate of different concentrations (10-5, 10-4, 10-3, 10-2 and 2 x 10-2 M) was used, and in the second, next to the lead acetate EDTA concentration of 0.012 % was added. The results of this study in which natural conditions are imitated showed that the percentage of alfalfa seed germination decreases with increasing lead-acetate concentrations. In a medium of high concentration of lead acetate 10-2 and 2 x 10-2, a small number of seeds (39% and 32 (32%) germinated. In the same treatments with EDTA, the toxic effects of lead acetate were reduced, and seed germination was better (59% and 43% seeds germinated). It has been noticed that lead has toxic effects on the growth of alfalfa roots and stems. In the variant in which EDTA was used, the negative influence of lead on and growth of alfalfa seedlings was significantly mitigated.

Influence of lead acetate on seed germination and growth of young alfalfa plants

This study presents the results of testing the effect of different concentrations of lead-acetate on seed germination and young Seedlings of alfalfa. Тhe experiment was organized so that in the first variant, only lead-acetate of different concentrations (10-5, 10-4, 10-3, 10-2 and 2 x 10-2 M) was used, and in the second, next to the lead acetate EDTA concentration of 0.012 % was added. The results of this study in which natural conditions are imitated showed that the percentage of alfalfa seed germination decreases with increasing lead-acetate concentrations. In a medium of high concentration of lead acetate 10-2 and 2 x 10-2, a small number of seeds (39% and 32 (32%) germinated. In the same treatments with EDTA, the toxic effects of lead acetate were reduced, and seed germination was better (59% and 43% seeds germinated). It has been noticed that lead has toxic effects on the growth of alfalfa roots and stems. In the variant in which EDTA was used, the negative influence of lead on and growth of alfalfa seedlings was significantly mitigated.

Combination of NOS- and PDK-Inhibitory Activity: Possible Way to Enhance Antitumor Effects

We have previously demonstrated a high antitumor potential of NOS inhibitor T1023 (1-isobutanoyl-2-isopropylisothiourea hydrobromide): antitumor antiangiogenic activity in several animal tumor models and its ability to synergistically enhance the antitumor effects of bevacizumab, cyclophosphamide and γ-radiation. At the same time, rather rapid adaptation of experimental neoplasias to T1023 treatment was often observed. We attempted to enhance the antitumor activity of this NOS inhibitor by supplementing its molecular structure with a PDK-inhibiting fragment, dichloroacetate (DCA), which is capable of hypoxia-oriented toxic effects. We synthesized compound T1084 (1-isobutanoyl-2-isopropylisothiourea dichloroacetate). Its toxic properties, NOS-inhibiting and PDK-inhibiting activity in vivo, and antitumor activity on the mouse Ehrlich carcinoma model (SEC) were investigated in compare with T1023 and Na-DCA. We found that the change of the salt-forming acid from HBr to DCA does not increase the toxicity of 1-isobutanoyl-2-isopropylisothiourea salts, but significantly expands the biochemical and anti-tumor activity. New compound T1084 realizes in vivo NOS-inhibiting and PDK-inhibiting activity, quantitatively, at the level of the previous compounds, T1023 and Na-DCA. In two independent experiments on SEC model, a pronounced synergistic antitumor effect of T1084 was observed in compare with T1023 and Na-DCA at equimolar doses. There were no signs of SEC adaptation to T1084 treatment, while experimental neoplasia rapidly desensitized to the separate treatment of both T1023 and Na-DCA. The totality of the data obtained indicates that the combination of antiangiogenic and hypoxia-oriented toxic effects (in this case, within the molecular structure of the active substance) can increase the antitumor effect and suppress the development of hypoxic resistance of neoplasias. In general, the proposed approach can be used for the design of new anticancer agents.

Comparison of cytotoxicity effects induced by four different types of nanoparticles in human corneal and conjunctival epithelial cells

The impact of particulate matter (PM) on ocular surface health has attracted increased attention in recent years. Previous studies have reported that differences in the chemical composition of PM can affect the toxicological response. However, available information on the toxic effects of chemical components of PM on the ocular surface is insufficient. In this paper, we aimed to investigate the toxicity effects of chemical components of PM on the ocular surface, focusing on the effects of four different types of nanoparticles (NPs) in human corneal epithelial cells (HCECs) and human conjunctival epithelial cells (HCjECs), which include titanium dioxide (TiO2), carbon black (CB), zinc dioxide (ZnO), and silicon dioxide (SiO2). We found that the in vitro cytotoxic effects of CB, ZnO, and SiO2 NPs are dependent on particle properties and cell type as well as the exposure concentration and time. Here, the order of increasing toxicity was SiO2 → CB → ZnO, while TiO2 demonstrated no toxicity. Moreover, toxic effects appearing more severe in HCECs than HCjECs. Reactive oxygen species (ROS)-mediated oxidative stress plays a key role in the toxicity of these three NPs in HCECs and HCjECs, leading to apoptosis and mitochondrial damage, which are also important contributors to aging. Sirtuin1 (SIRT1) as an NAD+-dependent protein deacetylase that seems to play a potential protective role in this process. These findings implied that ROS and/or SIRT1 may become a potential target of clinical treatment of PM- or NP-related ocular surface diseases.

PLGA/PEG Nanoparticles Loaded with Cyclodextrin-Peganum harmala Alkaloid Complex and Ascorbic Acid with Promising Antimicrobial Activities

Antimicrobial drugs face numerous challenges, including drug resistance, systemic toxic effects, and poor bioavailability. To date, treatment choices are limited, which warrants the search for novel potent antivirals, including those extracted from natural products. The seeds of Peganum harmala L. (Zygophyllaceae family) have been reported to have antimicrobial, antifungal, and anticancer activities. In the present study, a 2-hydroxy propyl-β-cyclodextrin (HPβCD)/harmala alkaloid-rich fraction (HARF) host–guest complex was prepared using a thin-film hydration method to improve the water solubility and bioavailability of HARF. The designed complex was then co-encapsulated with ascorbic acid into PLGA nanoparticles coated with polyethylene glycol (HARF–HPßCD/AA@PLGA-PEG NPs) using the W/O/W multiple emulsion-solvent evaporation method. The average particle size, PDI, and zeta potential were 207.90 ± 2.60 nm, 0.17 ± 0.01, and 31.6 ± 0.20 mV, respectively. The entrapment efficiency for HARF was 81.60 ± 1.20% and for ascorbic acid was 88 ± 2.20%. HARF–HPßCD/AA@PLGA-PEG NPs had the highest antibacterial activity against Staphylococcus aureus and Escherichia coli (MIC of 0.025 mg/mL). They also exhibited high selective antiviral activity against the H1N1 influenza virus (IC50 2.7 μg/mL) without affecting the host (MDCK cells). In conclusion, the co-encapsulation of HPCD–HARF complex and ascorbic acid into PLGA-PEG nanoparticles significantly increased the selective H1N1 killing activity with minimum host toxic effects.