Toxicological Effects Research Articles

Melittin—The principal toxin of honeybee venom—Is also produced in the honeybee fat body

Melittin is a powerful toxin present in honeybee venom that is active in a wide range of animals, from insects to humans. Melittin exerts numerous biological, toxicological, and pharmacological effects, the most important of which is destruction of the cell membrane. The phospholipase activity of melittin and its ability to activate phospholipases in the venom contribute to these actions. Using analytical methods, we discovered that the honeybee Apis mellifera produces melittin not only in the venom gland but also in its fat body cells, which remain resistant to this toxin's effects. We suggest that melittin acts as an anti-bacterial agent, since its gene expression is significantly upregulated when honeybees are infected with Escherichia coli and Listeria monocytogenes bacteria; additionally, melittin effectively kills these bacteria in the disc diffusion test. We hypothesize that the chemical and physicochemical properties of the melittin molecule (hydrophilicity, lipophilicity, and capacity to form tetramers) in combination with reactive conditions (melittin concentration, salt concentration, pH, and temperature) are responsible for the targeted destruction of bacterial cells and apparent tolerance towards own tissue cells. Considering that melittin is an important current and, importantly, potential broad-spectrum medication, a thorough understanding of the observed phenomena may significantly increase its use in clinical practice.

Medium-chain chlorinated paraffins (MCCPs) induce renal cell aging and ferroptosis.

Medium-chained chlorinated paraffins (MCCPs) are a class of chlorinated derivatives of straight-chain n-alkanes with complex compositions, which are widely used in industry. The chlorinated paraffins (CPs) are divided into short chain chlorinated paraffins (SCCPs), medium chain chlorinated paraffins (MCCPs) and long chain chlorinated paraffins (LCCPs). SCCPs have been banned due to their severe bioaccumulation and biotoxicity. Therefore, MCCPs are used as a substitute for SCCPs. However, the toxicological data of MCCPs are still very limited. For this, we systematically investigated the toxicological impact of MCCPs on a renal cell model in the current study. Our work provides basic research data for analyzing the toxicological effects of MCCPs, suggesting that MCCPs should be restricted in their usage. A series of biochemical experiments was performed, including Western blot, indirect immunofluorescence assay, and ELISA was performed to analyze the toxicological effects of MCCPs. Two renal cell lines were used as a model for assessing the toxicological effects of MCCPs. Cell proliferation assays showed that MCCPs could inhibit the proliferation of kidney cells in a dose-dependent manner. Further studies showed that MCCPs induced ferroptosis in kidney cells by evaluating a series of ferroptosis marker molecules. Additionally, MCCPs induced inflammatory response and premature senescence in HEK293 and NRK-52E cells. Molecular mechanism experiments showed that ferroptosis induced by MCCPs emerged as a significant contributor to premature aging of kidney cells. The current study provides basic research data to analyze the toxicological effects of MCCPs and their toxicity mechanisms. It also provides a theoretical basis for the assessment of the potential ecological risk of MCCPs, as well as basic experimental data for the rational and standardized use of MCCPs.

Influence of plants and spices on the formation of biogenic amines in meat

Biogenic amines (BAs) consist of organic nitrogenous compounds produced by the amino acid’s decarboxylation. They are present in various foods, such as meat products, and are associated with several health hazards. In meat, BAs are produced by the action of microorganisms that can decarboxylate amino acids. BAs can also be produced in meat naturally by enzymatic pathways. Tyramine, histamine, cadaverine, and putrescine are BAs frequently found in meat products. BAs are frequently found in fish depending on the species and time-temperature control, but can also be present in meat, particularly in canned, cured and fermented meat products. BAs are associated with various health disorders and toxicological effects including cardiovascular, respiratory and gastrointestinal system problems. Numerous factors influence the BAs generation in meat products. Factors such a handling, storage temperature, and processing procedures are essential for minimizing the risk of BAs formation to ensure food safety. Plant extracts and spices, play a multifaceted role in regulating BAs developments in diverse food items. Plant extracts containing phenolic/polyphenols, terpenoids and alkaloids have exhibited antimicrobial properties that can hinder the growth of microorganisms responsible for producing amines, consequently reducing BAs formation. Also, spices frequently contain compounds that impede the enzymatic conversion of precursor amino acids into biogenic amines.

Enantioselective bioaccumulation and toxicological effects of chiral neonicotinoid sulfoxaflor in rats

Sulfoxaflor is a widely used fourth-generation neonicotinoid pesticide, which has been detected in biological and environmental samples. Sulfoxaflor can potentially be exposed to humans via the food chain, thus understanding its toxic effects and enantioselective bioaccumulation is crucial. In this study, toxicokinetics, bioaccumulation, tissue distribution and enantiomeric profiles of sulfoxaflor in rats were investigated through single oral exposure and 28-days continuous exposure experiment. Sulfoxaflor mainly accumulated in liver and kidney, and the (−)-2R,3R-sulfoxaflor and (−)-2S,3R-sulfoxaflor had higher enrichment than their enantiomers in rats. The toxicological effects were evaluated after 28-days exposure. Slight inflammation in liver and kidney were observed by histopathology. Sphingolipid, amino acid, and vitamin B6 metabolism pathways were significantly disturbed in metabonomics analysis. These toxicities were in compliance with dose-dependent effects. These results improve understanding of enantioselective bioaccumulation and the potential health risk of sulfoxaflor.

Regrettable substitution? Comparative study of the effect profile of bisphenol A and eleven analogues in an in vitro test battery

BackgroundBisphenol A (BPA) is currently one of the most widely used synthetic chemicals in the production of a wide range of plastics. Due to its diverse endocrine disrupting potential alternative bisphenols, also referred to as analogues, have been developed. Although the toxicity of BPA is well studied, the (eco)toxicological effects of the bisphenol analogues are largely unknown. The similar molecular structure of the analogues suggests comparable toxicological effects. This study aims to extend the (eco)toxicological knowledge on the bisphenol analogues by evaluating eleven bisphenol analogues compared to the reference substance BPA in in vitro bioassays. The examined endpoints are endocrine potential on three nuclear receptors in recombinant yeast cells of Saccharomyces cerevisiae, baseline toxicity (also referred to as non-specific toxicity, describing the minimal toxicity of a chemical) in the luminescent bacterium Aliivibrio fischeri, and mutagenicity in two strains of Salmonella typhimurium.ResultsBisphenol A showed estrogenic and anti-androgenic activity at EC50 concentrations of 0.516 mg/L (2.26 × 10–6 M) and 1.06 mg/L (4.63 × 10–6 M), respectively. The assays confirmed notable estrogenic and anti-androgenic activity for the vast majority of analogues in comparable, and often higher, efficacies to BPA. Some analogues showed anti-estrogenic instead of estrogenic activity in a range from 0.789 mg/L (1.45 × 10–6 M; TBBPA) to 2.69 mg/L (2.46 × 10–6 M; BADGE). The baseline toxicity of the analogues revealed a similar tendency of comparable to more prominent effects compared to BPA, ranging from 5.81 mg/L (1.73 × 10–5 M; BPAF) to 39.1 mg/L (1.56 × 10–4 M; BPS). There was no evidence of mutagenicity found.ConclusionThe examined bisphenol analogues prove to be equally, if not more, problematic in endocrine activities than the reference bisphenol A. Based on these results, the tested bisphenols cannot be regarded as safer alternatives and reinforce the notion of bisphenol analogues being considered as regrettable substitutions.

Individual cytotoxicity of three major type A trichothecene, T-2, HT-2, and diacetoxyscirpenol in human Jurkat T cells

Mycotoxins are toxic, fungal secondary metabolites that contaminate agricultural commodities, food, and feed. Among them, T-2, HT-2, and diacetoxyscirpenol (DAS; the major type A trichothecene) are primarily produced from Fusarium species. These mycotoxins exert numerous toxicological effects in animals and humans, such as dermatotoxicity, haematotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity, and immunotoxicity. In the present study, human Jurkat T cells were used as a model to investigate apoptotic cell death induced by T-2, HT-2, and DAS. The results showed that T-2, HT-2, and DAS decreased cell viability and increased production of Reactive Oxygen Species in a time- and dose-dependency. Based on their IC50 values, they could be ranked in decreasing order of cytotoxicity as T-2 > HT-2 > DAS. All tested mycotoxins caused DNA fragmentation, up-regulated cytochrome C, caspase 3, and caspase 9 mRNA levels, and down-regulated the relative expression of Bcl-2 and caspase 8. The effects of these trichothecenes on apoptosis were determined based on flow cytometry. At the IC50 concentrations, the percentages of apoptotic cells were significantly higher than for the controls. Taken together, these data suggested that T-2, HT-2, and DAS could induce apoptosis through the mitochondrial apoptotic pathway.

Broad-scale pesticide screening finds anticoagulant rodenticide and legacy pesticides in Australian frogs

Pesticide contamination poses a significant threat to non-target wildlife, including amphibians, many of which are already highly threatened. This study assessed the extent of pesticide exposure in dead frogs collected during a mass mortality event across eastern New South Wales, Australia between July 2021 and March 2022. Liver tissue from 77 individual frogs of six species were analysed for >600 legacy and contemporary pesticides, including rodenticides. More than a third (36 %) of the liver samples contained at least one of the following pesticides: brodifacoum, dieldrin, DDE, heptachlor/heptachlor epoxide, fipronil sulfone, and 2-methyl-4-chlorophenoxyacetic acid (MCPA). Brodifacoum, a second-generation anticoagulant rodenticide, was found in four of the six frog species analysed: the eastern banjo frog (Limnodynastes dumerilii), cane toad (Rhinella marina), green tree frog (Litoria caerulea) and Peron's tree frog (Litoria peronii). This is the first report of anticoagulant rodenticide detected in wild amphibians, raising concerns about potential impacts on frogs and extending the list of taxa shown to accumulate rodenticides. Dieldrin, a banned legacy pesticide, was also detected in two species: striped marsh frog (Limnodynastes peronii) and green tree frog (Litoria caerulea). The toxicological effects of these pesticides on frogs are difficult to infer due to limited comparable studies; however, due to the low frequency of detection the presence of these pesticides was not considered a major contributing factor to the mass mortality event. Additional research is needed to investigate the effects of pesticide exposure on amphibians, particularly regarding the impacts of second-generation anticoagulant rodenticides. There is also need for continued monitoring and improved conservation management strategies for the mitigation of the potential threat of pesticide exposure and accumulation in amphibian populations.

All Roads Lead to Rome: Comparing Nanoparticle- and Small Molecule-Driven Cell Autophagy.

Autophagy, vital for removing cellular waste, is triggered differently by small molecules and nanoparticles. Small molecules, like rapamycin, non-selectively activate autophagy by inhibiting the mTOR pathway, which is essential for cell regulation. This can clear damaged components but may cause cytotoxicity with prolonged use. Nanoparticles, however, induce autophagy, often causing oxidative stress, through broader cellular interactions and can lead to a targeted form known as "xenophagy." Their impact varies with their properties but can be harnessed therapeutically. In this review, the autophagy induced by nanoparticles is explored and small molecules across four dimensions: the mechanisms behind autophagy induction, the outcomes of such induction, the toxicological effects on cellular autophagy, and the therapeutic potential of employing autophagy triggered by nanoparticles or small molecules. Although small molecules and nanoparticles each induce autophagy through different pathways and lead to diverse effects, both represent invaluable tools in cell biology, nanomedicine, and drug discovery, offering unique insights and therapeutic opportunities.

Harnessing machine learning to predict cytochrome P450 inhibition through molecular properties.

Cytochrome P450 enzymes are a superfamily of enzymes responsible for the metabolism of a variety of medicines and xenobiotics. Among the Cytochrome P450 family, five isozymes that include 1A2, 2C9, 2C19, 2D6, and 3A4 are most important for the metabolism of xenobiotics. Inhibition of any of these five CYP isozymes causes drug-drug interactions with high pharmacological and toxicological effects. So, the inhibition or non-inhibition prediction of these isozymes is of great importance. Many techniques based on machine learning and deep learning algorithms are currently being used to predict whether these isozymes will be inhibited or not. In this study, three different molecular or substructural properties that include Morgan, MACCS and Morgan (combined) and RDKit of the various molecules are used to train a distinct SVM model against each isozyme (1A2, 2C9, 2C19, 2D6, and 3A4). On the independent dataset, Morgan fingerprints provided the best results, while MACCS and Morgan (combined) achieved comparable results in terms of balanced accuracy (BA), sensitivity (Sn), and Mathews correlation coefficient (MCC). For the Morgan fingerprints, balanced accuracies (BA), Mathews correlation coefficients (MCC), and sensitivities (Sn) against each CYPs isozyme, 1A2, 2C9, 2C19, 2D6, and 3A4 on an independent dataset ranged between 0.81 and 0.85, 0.61 and 0.70, 0.72 and 0.83, respectively. Similarly, on the independent dataset, MACCS and Morgan (combined) fingerprints achieved competitive results in terms of balanced accuracies (BA), Mathews correlation coefficients (MCC), and sensitivities (Sn) against each CYPs isozyme, 1A2, 2C9, 2C19, 2D6, and 3A4, which ranged between 0.79 and 0.85, 0.59 and 0.69, 0.69 and 0.82, respectively.

Development of an HPLC-PDA Method for the Simultaneous Estimation of Three Antibiotics in Pharmaceutical Formulations and Bovine Milk and Health Risk Assessment

A simple new, rapid, sensitive, and cost-effective HPLC–PDA method was developed and validated for the determination of tetracycline (TC), oxytetracycline (OTC), and ciprofloxacin (CIP) simultaneously. Chromatographic separations were carried out using a reversed-phase Shim-pack GIS C18 column (4.60 × 250.00 mm; 5.00 µm) at 30°C. Oxalic acid (0.05 M), acetonitrile, and methanol were used as mobile phase under gradient elution conditions at the flow rate of 1.50 mL min−1. Detection wavelength was set at 330 nm. An aliquot of 20.00 µL solution was injected, and three drugs were eluted within 7.39 ± 0.05 min. As per ICH guidelines linearity, recovery, accuracy, precision, selectivity, specificity, sensitivity, stability, column efficiency, system suitability, and robustness were determined for the validation of the proposed method. Calibration curves were linear over a studied concentration range of 8.00 µg mL−1 with a correlation coefficient (r) of 0.999 for all drugs. Relative standard deviation (RSD) for intra− and interday precision was found less than 2.87% and 3.22%, respectively, indicating the method to be reproducible. The proposed method has been suitably applied for the estimation of TC, OTC, and CIP in pharmaceutical formulation and milk samples collected from local market in Bangladesh. Among 15 milk samples analyzed, most of the cases (more than 50%) TC, OTC, and CIP were detected above maximum residue levels (MRLs) though no significant toxicological effect on the health of consumers in the study area was identified.

Peptide-Based Recognition Agents of Histamine: A Biopanning Approach with Enhanced Specificity.

Histamine is a biogenic amine that poses a potential threat to public health due to its toxicological effects. In this study, we identified histamine-binding peptides by screening a random 12-mer peptide library, employing a novel biopanning approach that excluded histidine-binding sequences in the final round. This additional step enhanced the selectivity of the peptides and prevented interference from histidine during detection. The binding affinities of synthesized peptides to histamine were assessed using isothermal titration calorimetry (ITC). Among the identified peptides, HBF10 (SGFRDGIEDFLW) and HBF26 (IPLENQHKIYST) showed significant affinity to histamine, with Kavalues of 2.56×104 (M-1) and 8.94×104 (M-1), respectively. Notably, the identified peptides did not demonstrate binding affinity towards histidine, despite its structural similarity to histamine. Subsequently, the surface plasmon resonance (SPR) sensor surface was prepared by immobilizing the peptide HBF26 to investigate the potential of the peptide as a recognition agent for histamine detection. The findings suggest that the identified peptides have an affinity to histamine specifically, showcasing their potential applications as diagnostic agents with specific targeting capabilities.

Dimethylcyclosiloxanes in Mobile Smart Terminal Devices: Concentrations, Distributions, Profiles, and Environmental Emissions.

Dimethylcyclosiloxanes (DMCs) are utilized as vital monomers in the synthesis of organosilicon compounds, integral to the manufacture of mobile smart terminal devices. Toxicological studies have revealed potential endocrine-disrupting activity, reproductive toxicity, neurotoxicity, and other toxicities of the DMCs. This study investigated the concentrations and composition profiles of seven DMCs, including hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), dodecamethylcyclohexasiloxane (D6), and tetradecamethylcycloheptasiloxane (D7), hexadecamethylcyclooctasiloxane (D8), and octadecamethylcyclononasiloxane (D9) in three types of mobile smart terminal device components (silicone rubber, adhesive, and plastics). Environmental emissions of DMCs from silicone rubber materials were also estimated to improve the recognition of their potential fate within the environment. D5-D9 were widely present in silicone rubber and adhesives with detection rates ranging from 91-95.5% and 50-100%, respectively, while D3 and D4 were more frequently detected in plastics, both showing a detection rate of 61.1%. Silicone rubber had the highest total DMCs (∑7DMCs) and a concentration of 802.2 mg/kg, which were dominated by D7, D8, and D9. DMCs detected in adhesives were dominated by D4, D5, and D6. The estimated emission of ∑DMCs released into the environment in China from silicone rubber used in mobile smart terminal devices exceeds 5000 tons per year. Further studies are needed on the presence of DMCs in various commodities and environmental media to assess their ecological and human health impacts, as well as the toxicological effects of D7-D9 for the appropriate regulation of these chemicals.

In vitro toxicological evaluation of glo menthol and non-menthol heated tobacco products

Heated tobacco products (HTPs) are non-combustible, inhaled tobacco products that generate an aerosol with fewer and lower levels of toxicants, with a potential to reduce risk relative to cigarette smoking. Here, we assessed in vitro toxicological effects of three menthol (glo neo neoCLICK, neo Smooth Menthol and Fresh Menthol) and one non-menthol (neo Smooth Tobacco) variants of glo HTP, along with market comparators for cigarettes and HTPs. Limited chemical characterization of the study products revealed significantly lower levels of acetaldehyde, acrolein, crotanaldehyde and formaldehyde in test samples from HTPs than those from cigarettes. The glo HTPs were non-mutagenic in the bacterial reverse mutagenesis assay. Although, the whole aerosol exposures of glo HTPs were classified as genotoxic in the in vitro micronucleus assay, and cytotoxic in the NRU (monolayer) and MTT (3 dimensional EpiAirway™ tissues) assays, the cigarette comparators were the most toxic study products in each of these assessments. Further, glo HTPs elicited oxidative stress responses only at the highest dose tested, whereas the cigarette comparators were potent inducers of oxidative stress at substantially lower doses in the EpiAirway tissues. The comparator (non-glo) HTP results were similar to the glo HTPs in these assays. Thus, the glo HTPs exhibit substantially lower toxicity compared to cigarettes.

Toxicological and Sedative Effects of Chipilin (Crotalaria longirostrata) Leaf Extracts Obtained by Maceration and Supercritical Fluid Extraction.

Chipilin (Crotalaria longirostrata) is consumed as a vegetable in the preparation of traditional dishes. As a folk medicine, Chipilin extracts are used as a hypnotic and sedative agent; however, there are few reports that support these uses. This study aimed to characterize the compounds present in Chipilin leaf extracts and to investigate their sedative effect using zebrafish as an in vivo model. Extracts were obtained by maceration with water (H2O), ethanol (EtOH), and EtOH-H2O, while oleoresin was obtained by supercritical fluid extraction (SFE). Total phenolic and flavonoid contents were quantified by colorimetric methods. Phytochemical constituents were identified by gas chromatography-mass spectrometry (GC-MS) analysis. The chronic and acute toxicities of Chipilin extracts were tested in zebrafish embryos and larvae, respectively. Chipilin sedative effect was tested by the larvae response to dark-light-dark transitions. EtOH-H2O extracts had the highest value of total phenolics (5345 ± 5.1 μg GAE/g), followed by water and oleoresin (1815 ± 5.1 and 394 ± 5.1 μg GAE/g, respectively). In water extracts were identified the alkaloid trachelanthamidine, 1,2β-epoxy- and the alkyl ketone 7,9-di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione, while oleamide, α-monostearin, and erucamide were detected in all samples except in water extracts. Oleoresin extract had the lowest embryotoxicity (LC50 = 4.99 μg/mL) and the highest sedative effects. SFE is a green alternative to obtain Chipilin extracts rich in erucamide, an endocannabinoid analogue, which plays an important role in the development of the central nervous system and in modulating neurotransmitter release.

Eco-toxicological and climate change effects of sludge thermal treatments: Pathways towards zero pollution and negative emissions

The high moisture content and the potential presence of hazardous organic compounds (HOCs) and metals (HMs) in sewage sludge (SS) pose technical and regulatory challenges for its circular economy valorisation. Thermal treatments are expected to reduce the volume of SS while producing energy and eliminating HOCs. In this study, we integrate quantitative analysis of SS concentration of 12 HMs and 61 HOCs, including organophosphate flame retardants (OPFRs) and per- and poly-fluoroalkyl substances (PFAS), with life-cycle assessment to estimate removal efficiency of pollutants, climate change mitigation benefits and toxicological effects of existing and alternative SS treatments (involving pyrolysis, incineration, and/or anaerobic digestion). Conventional SS treatment leaves between 24 % and 40 % of OPFRs unabated, while almost no degradation occurs for PFAS. Thermal treatments can degrade more than 93% of target OPFRs and 95 % of target PFAS (with the rest released to effluents). The different treatments affect how HMs are emitted across environmental compartments. Conventional treatments also show higher climate change impacts than thermal treatments. Overall, thermal treatments can effectively reduce the HOCs emitted to the environment while delivering negative emissions (from about −56 to −111 kg CO2-eq per tonne of sludge, when pyrolysis is involved) and producing renewable energy from heat integration and valorization.

Reproductive performance of freshwater snail, Helisoma duryi under the effect of bulk and nano zinc oxide.

Nanotechnology has been used to apply nanoparticle essential elements to enhance the ability of animals to absorb these elements and consequently improve their reproductive performance. High concentrations of nanoparticles (NPs) can directly harm a range of aquatic life forms, ultimately contributing to a decline in biodiversity. Helisoma duryi snails are a good model for studying the toxicological effects of bulk zinc oxide (ZnO-BPs) and nano zinc oxide (ZnO-NPs) on freshwater gastropods. This study aimed to compare the toxic effects of ZnO-BPs and ZnO-NPs on H. duryi snails and explore how waterborne and dietary exposure influenced the reproductive performance of this snail. ZnO-BPs and ZnO-NPs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray powder (XRD). This study revealed that the size of ZnO-BPs and ZnO-NPs were 154 nm and 11-31 nm, respectively. The results showed that exposure of adult snails to sub-lethal concentrations of both ZnO forms (bulk and nano) for 24 h/week for 4 weeks markedly changed their reproductive performance in a concentration-dependent manner, where fecundity was negatively affected by high concentrations. It was concluded that dietary exposure to the lowest tested concentration of ZnO-NPs (1 ppm) has a positive effect as the number of eggs and egg masses/snails increased and the incubation period decreased. Also, poly-vitelline eggs (The formation of twins) were observed. ZnO-NPs at low concentrations positively affect the reproductive performance of snails, especially after dietary exposure. The results revealed that 1 ppm ZnO-NPs could be supplementary provided to snails to improve their fertility, reduce the developmental time course, increase hatchability percentage, and produce poly-vitelline eggs.

Unraveling the ecotoxicological effects of micro and nano-plastics on aquatic organisms and human health

Plastic pollution ranks among the most severe environmental disasters caused by humans, generating millions of tonnes of waste annually. The extensive and unregulated use of plastics has led to ecotoxicity and environmental imbalance. Microplastics (MPs) are prevalent in aquatic environments, and these MPs further degrade into even smaller particles known as nano-plastics (NPs). Both MPs and NPs impact the environment by readily absorbing organic pollutants and pathogens from their surroundings, owing to their bigger surface area to volume ratio. This review focuses on the source of origin, bioaccumulation, and potential impact of MPs and NPs on aquatic organisms and human health. Additionally, the review explores various methods employed for identification and quantification of these particles in aquatic ecosystems. Sufficient information is available on their characteristics, distributions, and effects on marine ecosystems compared with freshwater ecosystems. For plastic particles <10 μm, more toxicological effects were observed compared with larger size particles, in aquatic life. Understanding the mechanism of action and ecotoxicological effects of micro/nano-plastics on the health of aquatic life across various trophic levels, as well as human health, is of utmost importance. We address knowledge gaps and provide insights into future research approaches for a better understanding of the interactive mechanisms between binary pollutants.

Lnc-Clic5 as a sponge for miR-212–5p to inhibit cow barn PM2.5-induced apoptosis in rat alveolar macrophages

Particulate matter 2.5 (PM2.5) is a highly hazardous airborne particulate matter that poses a significant risk to humans and animals. Urban airborne particulate matter contributes to the increased incidence and mortality of respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), in humans. However, the specific mechanism by which PM2.5 affects animals in barn environments is yet to be elucidated. In this study, we investigated the effect of exposure to cow barn PM2.5 on rat alveolar macrophages (NR8383) and found that it induced apoptosis via the miR-212–5p/RASSF1 pathway. We found that lnc-Clic5 expression was downregulated in NR8383 cells exposed to cow barn PM2.5. Lnc-Clic5 plays a competitive endogenous RNA (ceRNA) regulatory role by sponging miR-212–5p to attenuate the regulation of RASSF1. Moreover, lnc-Clic5 overexpression inhibited NR8383 apoptosis by targeting the miR-212–5p/RASSF1 pathway. Co-treatment with miR-212–5p and lnc-Clic5 in the presence of cow barn PM2.5 revealed that lnc-Clic5 reversed NR8383 cell apoptosis induced by PM2.5 when miR-212–5p was overexpressed. These findings contribute to the study of ncRNAs and ceRNAs regulating PM2.5-induced apoptosis in animal farms, provide therapeutic targets for lung macrophage apoptosis, and may be useful for further evaluating the toxicological effects of PM2.5 in farmhouses on the respiratory systems of humans and animals.

COMPUTER PREDICTION OF PHARMACOLOGICAL ACTIVITY OF SOLANUM TUBEROSUM L. ALKALOIDS

The alkaloids solanine and chaconine were discovered in 1821. However, its did not find medical use due to toxicity. At present, modern research methods have revealed anti-cancer activity of the alcaloids. In this regard, the hypothesis of the presence of other previously unexplored pharmacological effects has arisen. The aim of the study is to predict new possible pharmacological and toxicological effects of alkaloids solanine and chaconine by computer modeling. Material and methods. The Reaxys database was used to identify known types of pharmacologic activity, online services with free access PASS, Swiss Target Prediction, Similarity ensemble approach (SEA) were used to identify new potential activities. They provided a list of potential targets, among which we selected the most promising one. Based on this, we further investigated the interaction of glycoalkaloids with the identified target by molecular docking. Results. The results obtained using the above online services correspond the literature data. However sigma-1 non-opioid intracellular receptor was identified as a new promising target. There is no experimental confirmation of the interaction between the tested compounds for this target. As a result of docking, the binding energy of solanine and chaconine with sigma-1 opioid receptors is comparable to that of the comparison drug, haloperidol. Conclusion. Solanine and chaconine may be active against sigma-1 receptors; however, the docking results need to be confirmed

The effect of pollutants on the ichthyofauna of Lake Ladoga and preventive measures

Lake Ladoga is the largest body of water in Europe with huge reserves of drinking water, and has a particularly important sanitary and hygienic significance for the Northwestern region of Russia. The lake has significant fishery importance – annual catches reached 6000 tons. per year. However, over the past few decades, the fishery status of the reservoir has changed significantly. Stocks and catches of the most valuable fish species have sharply decreased as a result of anthropogenic impact – pollution and eutrophication.Chemical-analytical studies of samples of water, bottom sediments, atmospheric precipitation and fish for metals were carried out in the laboratory of fishery ecology of the St. Petersburg branch of the Federal State Budgetary Institution "VNIRO" ("GosNIORH" named after L.S. Berg) on an atomic absorption spectrophotometer AA - 7000 (Shimadzu) according to approved methods (PNDF., 2010; M02-2406., 2013 and M02-902-125, 2005), and in the research laboratory of food and natural objects "ANALECT" of the Institute of the Ministry of Health of the Russian Federation, using the method of atomic absorption spectrometry according to approved methods. Hydrochemical and hydrological parameters were determined using an automatic multiparameter probe Aqua TROLL 500.The southern water area of the lake, which is the most valuable in terms of fisheries, turned out to be the most vulnerable to toxicological effects. Pollution of spawning grounds, toxicosis of fish, violation of natural reproduction in combination with the hydrological features of the reservoir have led to irreversible transformations in the structure of the ichthyofauna as a whole for the entire lake. Pronounced consequences for the ichthyofauna of the reservoir are associated with the sensitivity of fish to pollutants, their ability to accumulate pathological information over a long-life cycle. The hydrological features of the southern water area of Lake Ladoga, combined with the location of pollution sources and the routes of pollutants, make it difficult to carry out preventive measures in this most important fishery area.