Concentration-dependent Toxicity Research Articles

Accumulation of Nanoplastics in Biomphalaria glabrata Embryos and Transgenerational Developmental Effects

(1) Background: Nanoplastics are emerging environmental pollutants with potential toxic effects on aquatic organisms. This study investigates the toxicity of NPs in Biomphalaria glabrata, a freshwater snail species widely used as a bioindicator species in ecotoxicology studies.; (2) Methods: We exposed three generations (F0–F2) of B. glabrata snail embryos to different sizes of polystyrene nanoparticles and assessed responses.; (3) Results: We observed severe effects on F0 to F2 B. glabrata embryos, including size-dependent (30 to 500 nm) increases in mortality rates, size and dosage-dependent (1 to 100 ppm) effects on hatching rates with concentration-dependent toxicity in the 30 nm exposure group. The F2 generation embryos appear to be most responsive to detoxification (CYP450) and pollutant metabolism (HSP70) at 48-h-post-treatment (HPT), while our developmental marker (MATN1) was highly upregulated at 96-HPT. We also report a particle-size-dependent correlation in HSP70 and CYP450 mRNA expression, as well as enhanced upregulation in the offspring of exposed snails. We also observed significant reductions in hatching rates for F2.; (4) Conclusions: These findings indicate that F2 generation embryos appear to exhibit increased stress from toxic substances inherited from their parents and grandparents (F1 and F0). This study provides valuable insights into the impact of plastic particulate pollution on multiple generations and highlights the importance of monitoring and mitigating plastic waste.

Andrographis echioides mediated synthesis of ZnONPs: A mechanistic insight into their antibacterial and anticancer efficacy

Finding alternatives to traditional antibiotics has become crucial due to the emerging antibiotic resistance shown by various microorganisms. Metal nanoparticles are arising as one such alternative. This paper presents an efficient and environmentally benign approach for preparing ZnO nanoparticles via greener approaches using Andrographis echioides (L.) Nees leaf extract and unravel the possible applications and mechanisms behind their toxicity against Escherichia coli and Staphylococcus aureus. The characterization studies show a peak at 362 nm (λmax) in the UV–Vis spectroscopic measurement with a bandgap energy of 3.10 eV. Hexagonal wurtzite structure is revealed in the XRD investigation of Ae-ZnONPs with a crystallite size of ≈14 nm. Ae-ZnONPs’ spherical structure andtheir meansize ranging between 15 and 35 nm, areconfirmed by SEM and TEM assessment respectively. The FTIR analysis revealed various functional groups and molecular interactions of plant extract and Ae-ZnONPs. Investigation into the antibacterial mechanism of action of Ae-ZnONPs revealed that these nanoparticles exhibit bactericidal effect against Escherichia coli and Staphylococcus aureus through the means of generation of reactive oxygen species (ROS), causing elevated lipid peroxidation and breakage of the membrane, and subsequent events culminating in cell death. These nanoparticles showed distinct antioxidant properties by scavenging DPPH, SOD, ABTS, and FRAP free radicals. Ae-ZnONPs were biocompatible with human RBC indicating their biosafe nature. Cytotoxicity evaluation of Ae-ZnONPs alone revealed concentration-dependent toxicity towards HeLa cells while remaining non-toxic to normal cells at the maximal concentration (100 μg/mL), showcasing anticancer potential which was further elucidated via ROS, live/dead cell imaging, and apoptotic study. Molecular alterations in HeLa cells were investigated through RT-PCR that showed upregulation of apoptotic and downregulation of antiapoptotic genes. The comprehensive findings suggest that Ae-ZnONPs can be employed as alternatives to antibiotics which also exhibit potential as anticancer agents, laying the foundation for future extensive research in this domain.

Enzyme-glycosylated ovalbumin/chitosan oligosaccharide nanoparticles: Simulation of in vitro digestion for the targeted release of vitamin D3 and application for encapsulation in beverages

Vitamin D3 (VD3) was encapsulated in TGaseOVA–chitosan (COS) composite nanoparticles. Isothermal titration calorimetry was used to explain the hydrophobic interaction between TGaseOVA and VD3 at the molecular level. The 87.7 nm TGaseOVA–COS composite nanoparticles achieved an encapsulation efficiency of 96.34% and loading capacity of 4.68% for 9 μg/ml VD3. An in vitro digestion experiment revealed that TGaseOVA–COS–VD3 composite nanoparticles had good stability in simulated gastric fluid and only 32.67% of the composite nanoparticles were released in simulated intestinal fluid. Meanwhile, sodium dodecyl sulfate polyacrylamide gel electrophoresis confirmed that the composite nanoparticles had a release rate of 100% in simulated intestinal fluid. TGaseOVA–COS–VD3 composite nanoparticles had a VD3 concentration of 8.73 μg/ml after pasteurization, indicating that they provided substantial protection to VD3 during pasteurization. TGaseOVA–COS was subjected to a 1-month simulated shelf life test. High-performance liquid chromatography confirmed that it had a VD3 retention rate of 90%. The concentration-dependent toxicity of VD3 was detected by using Caco-2 cells. VD3 exhibited toxicity at the concentration of 11 μg/ml. Therefore, the embedding dose of 9 μg/ml used in this work was considered a safe dose. TGaseOVA–COS composite nanoparticles have excellent stability and good VD3 slow-release properties. They can be used in concentrated clear beverages and other food and beverage products. Therefore, they have potential for applications in the food and pharmaceutical industries.

Ultrasonic-assisted extraction of total flavonoids from Zanthoxylum bungeanum residue and their allelopathic mechanism on Microcystis aeruginosa

Water eutrophication has emerged as a pressing concern for massive algal blooms, and these harmful blooms can potentially generate harmful toxins, which can detrimentally impact the aquatic environment and human health. Consequently, it is imperative to identify a safe and efficient approach to combat algal blooms to safeguard the ecological safety of water. This study aimed to investigate the procedure for extracting total flavonoids from Z. bungeanum residue and assess its antioxidant properties. The most favorable parameters for extracting total flavonoids from Z. bungeanum residue were a liquid–solid ratio (LSR) of 20 mL/g, a solvent concentration of 60%, an extraction period of 55 min, and an ultrasonic temperature of 80 °C. Meanwhile, the photosynthetic inhibitory mechanism of Z. bungeanum residue extracts against M. aeruginosa was assessed with a particular focus on the concentration-dependent toxicity effect. Z. bungeanum residue extracts damaged the oxygen-evolving complex structure, influenced energy capture and distribution, and inhibited the electron transport of PSII in M. aeruginosa. Furthermore, the enhanced capacity for ROS detoxification enables treated cells to sustain their photosynthetic activity. The findings of this study hold considerable relevance for the ecological management community and offer potential avenues for the practical utilization of resources in controlling algal blooms.

Unveiling the molecular networks underlying cellular impairment in Saccharomyces cerevisiae: investigating the effects of magnesium oxide nanoparticles on cell wall integrity and endoplasmic reticulum stress response.

Nanoparticles, particularly magnesium oxide nanoparticles (MgO-NPs), are increasingly utilized in various fields, yet their potential impact on cellular systems remains a topic of concern. This study aimed to comprehensively investigate the molecular mechanisms underlying MgO-NP-induced cellular impairment in Saccharomyces cerevisiae, with a focus on cell wall integrity, endoplasmic reticulum (ER) stress response, mitochondrial function, lipid metabolism, autophagy, and epigenetic alterations. MgO-NPs were synthesized through a chemical reduction method, characterized for morphology, size distribution, and elemental composition. Concentration-dependent toxicity assays were conducted to evaluate the inhibitory effect on yeast growth, accompanied by propidium iodide (PI) staining to assess membrane damage. Intracellular reactive oxygen species (ROS) accumulation was measured, and chitin synthesis, indicative of cell wall perturbation, was examined along with the expression of chitin synthesis genes. Mitochondrial function was assessed through Psd1 localization, and ER structure was analyzed using dsRed-HDEL marker. The unfolded protein response (UPR) pathway activation was monitored, and lipid droplet formation and autophagy induction were investigated. Results demonstrated a dose-dependent inhibition of yeast growth by MgO-NPs, with concomitant membrane damage and ROS accumulation. Cell wall perturbation was evidenced by increased chitin synthesis and upregulation of chitin synthesis genes. MgO-NPs impaired mitochondrial function, disrupted ER structure, and activated the UPR pathway. Lipid droplet formation and autophagy were induced, indicating cellular stress responses. Additionally, MgO-NPs exhibited differential cytotoxicity on histone mutant strains, implicating specific histone residues in cellular response to nanoparticle stress. Immunoblotting revealed alterations in histone posttranslational modifications, particularly enhanced methylation of H3K4me. This study provides comprehensive insights into the multifaceted effects of MgO-NPs on S. cerevisiae, elucidating key molecular pathways involved in nanoparticle-induced cellular impairment. Understanding these mechanisms is crucial for assessing nanoparticle toxicity and developing strategies for safer nanoparticle applications.

Evaluating potential developmental toxicity of perfluoroalkyl and polyfluoroalkyl substances in Xenopus laevis embryos and larvae.

As part of the US Environmental Protection Agency's perfluoroalkyl and polyfluoroalkyl substances (PFAS) Action Plan, the agency is committed to increasing our understanding of the potential ecological effects of PFAS. The objective of these studies was to examine the developmental toxicity of PFAS using the laboratory model amphibian species Xenopus laevis. We had two primary aims: (1) to understand the developmental toxicity of a structurally diverse set of PFAS compounds in developing embryos and (2) to characterize the potential impacts of perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), and hexafluoropropylene oxide-dimer acid (HFPO-DA a.k.a. GenX), on growth and thyroid hormone-controlled metamorphosis. We employed a combination of static renewal and flow-through exposure designs. Embryos were exposed to 17 structurally diverse PFAS starting at the midblastula stage through the completion of organogenesis (96 h). To investigate impacts on PFOS, PFOA, PFHxS, and HFPO-DA on development and metamorphosis, larvae were exposed from premetamorphosis (Nieuwkoop Faber stage 51 or 54) through pro metamorphosis. Of the PFAS tested in embryos, only 1H,1H,10H,10H-perfluorodecane-1,10-diol (FC10-diol) and perfluorohexanesulfonamide (FHxSA) exposure resulted in clear concentration-dependent developmental toxicity. For both of these PFAS, a significant increase in mortality was observed at 2.5 and 5mg/L. For FC10-diol, 100% of the surviving embryos were malformed at 1.25 and 2.5mg/L, while for FHxSA, a significant increase in malformations (100%) was observed at 2.5 and 5mg/L. Developmental stage achieved was the most sensitive endpoint with significant effects observed at 1.25 and 0.625 mg/L for FC10-diol and FHxSA, respectively. In larval studies, we observed impacts on growth following exposure to PFHxS and PFOS at concentrations of 100 and 2.5mg/L, respectively, while no impacts were observed in larvae when exposed to PFOA and HFPO-DA at concentration of 100 mg/L. Further, we did not observe impacts on thyroid endpoints in exposed larvae. These experiments have broadened our understanding of the impact of PFAS on anuran development.

Toxic interactions at the physiological and biochemical levels of green algae under stress of mixtures of three azole fungicides

Assessing the interactions between environmental pollutants and these mixtures is of paramount significance in understanding their negative effects on aquatic ecosystems. However, existing research often lacks comprehensive investigations into the physiological and biochemical mechanisms underlying these interactions. This study aimed to reveal the toxic mechanisms of cyproconazole (CYP), imazalil (IMA), and prochloraz (PRO) and corresponding these mixtures on Auxenochlorella pyrenoidosa by analyzing the interactions at physiological and biochemical levels. Higher concentrations of CYP, IMA, and PRO and these mixtures resulted in a reduction in chlorophyll (Chl) content and increased total protein (TP) suppression, and malondialdehyde (MDA) content exhibited a negative correlation with algal growth. The activity of catalase (CAT) and superoxide dismutase (SOD) decreased with increasing azole fungicides and their mixture concentrations, correlating positively with growth inhibition. Azole fungicides induced dose-dependent apoptosis in A. pyrenoidosa, with higher apoptosis rates indicative of greater pollutant toxicity. The results revealed concentration-dependent toxicity effects, with antagonistic interactions at low concentrations and synergistic effects at high concentrations within the CYP-IMA mixtures. These interactions were closely linked to the interactions observed in Chl-a, carotenoid (Car), CAT, and cellular apoptosis. The antagonistic effects of CYP-PRO mixtures on A. pyrenoidosa growth inhibition can be attributed to the antagonism observed in Chl-a, Chl-b, Car, TP, CAT, SOD, and cellular apoptosis. This study emphasized the importance of gaining a comprehensive understanding of the physiological and biochemical interactions within algal cells, which may help understand the potential mechanism of toxic interaction.

Blend Electrospinning of Nigella sativa-Incorporating PCL/PLA/HA Fibers and Its Investigation for Bone Healing Applications.

One of the well-known postoperative complications that requires a number of prophylactic and curative treatments is infection. The implications of postsurgical infections are further exacerbated by the emergence of antibiotic-resistant strains. Reduced effectiveness of synthetic antibiotics has led to an interest in plant-based substances. Extracts obtained from Nigella sativa have been shown to possess effective anti-infectious agents against bacteria frequently seen in bone infections. In this study, a fiber-based bone scaffold containing polycaprolactone, poly(lactic acid), and hydroxyapatite with N. sativa oil at varying concentrations was developed. Solvent electrospinning was used to fabricate the fibers with the specified composition. According to FE-SEM analysis, fibers with average diameters of 751 ± 82, 1000 ± 100, 1020 ± 90, and 1223 ± 112 nm were formed and successful integration of N. sativa oil into the fiber's structure was confirmed via FTIR. Staphylococcus aureus showed moderate susceptibility against the fibers with a maximum inhibition zone diameter of 11.5 ± 1.6 mm. MTT assay analysis exhibited concentration-dependent cell toxicity against fibroblast cells. In short, the antibacterial fibers synthesized in this study possessed antibacterial properties while also allowing moderate accommodation of CDD fibroblast cells at low oil concentrations, which can be a potential application for bone healing and mitigating postsurgical infections.

Silver nanoparticles and silver/silica nanocomposites: Impacts on Z. mays L. growth, nutrient uptake and soil health

Although silver nanoparticles (Ag NPs) are widely employed in diverse industries, including agriculture, concerns about their adverse effects on plants at higher concentrations prompt exploration of alternatives, such as Ag/SiO2 NCs. Adding nano SiO2 is anticipated to create a complex with Ag+ ions, potentially decreasing their release into the environment and mitigating toxicity. The potential of Ag/SiO2 NCs as plant growth stimulants remains understudied to date. In this context, the study evaluates the impact of Ag/SiO2 NCs on 30-day-old Z. mays plants compared to Ag NPs at 100 and 200 ppm concentrations and on soil health. Soil health analysis revealed that both Ag NPs and Ag/SiO2 NCs supported the proliferation of P-solubilizing and N-fixing bacteria. Bioaccumulation analysis reveals higher Ag content in plants treated with Ag/SiO2 NCs, attributed to reduced agglomeration. Ag NPs exhibited concentration-dependent toxicity as 200 ppm hindered Z. mays growth, chlorophyll levels and absorption of P, Mg and K, whereas 100 ppm was found to be stimulatory. In stark contrast, Ag/SiO2 NCs demonstrated a remarkable capacity to mitigate Ag toxicity. The beneficial impact of Ag/SiO2 NCs on growth metrics, chlorophyll levels, lipid peroxidation, antioxidant enzyme activity and nutrient absorption was observed at both 100 and 200 ppm. However, it was more pronounced at 100 ppm concentration. This suggests that incorporating SiO2 in NCs may counteract the toxic effects of Ag, possibly through the complexation of Ag+ and a slower release mechanism.

Chemotherapeutics-Loaded Poly(Dopamine) Core-Shell Nanoparticles for Breast Cancer Treatment.

Chemophotothermal therapy is an emerging treatment of metastatic and drug-resistant cancer anomalies. Among various photothermal agents tested, poly(dopamine) provides an excellent biocompatible alternative that can be used to develop novel drug delivery carriers for cancer treatment. This study explores the synthesis of starch-encapsulated, poly(dopamine)-coated core-shell nanoparticles in a one-pot synthesis approach and by surfactant-free approach. The nanoparticles produced are embellished with polymeric stealth coatings and are tested for their physiologic stability, photothermal properties, and drug delivery in metastatic triple-negative breast cancer cell (TNBC) lines. Our results indicate that stealth polymer-coated nanoparticles exhibit superior colloidal stability under physiologic conditions, and are excellent photothermal agents, as determined by the increase in temperature of solution in the presence of nanoparticles, upon laser irradiation. The chemotherapeutic drug-loaded nanoparticles also showed concentration-dependent toxicities in TNBC and in a brain metastatic cell line. SIGNIFICANCE STATEMENT: This study develops, for the first time, biocompatible core-shell nanoparticles in a template-free approach that can serve as a drug delivery carrier and as photothermal agents for cancer treatment.

Distinct concentration-dependent oxidative stress profiles by cadmium in a rat kidney proximal tubule cell line

Levels and chemical species of reactive oxygen/nitrogen species (ROS/RNS) determine oxidative eustress and distress. Abundance of uptake pathways and high oxygen consumption for ATP-dependent transport makes the renal proximal tubule particularly susceptible to cadmium (Cd2+)-induced oxidative stress by targeting ROS/RNS generation or antioxidant defence mechanisms, such as superoxide dismutase (SOD) or H2O2-metabolizing catalase (CAT). Though ROS/RNS are well-evidenced, the role of distinct ROS profiles in Cd2+ concentration-dependent toxicity is not clear. In renal cells, Cd2+ (10–50 µM) oxidized dihydrorhodamine 123, reaching a maximum at 2–3 h. Increases (up to fourfold) in lipid peroxidation by TBARS assay and H2O2 by Amplex Red were evident within 30 min. ROS and loss in cell viability by MTT assay with 50 µM Cd2+ could not be fully reversed by SOD mimetics Tempol and MnTBAP nor by SOD1 overexpression, whereas CAT expression and α-tocopherol were effective. SOD and CAT activities were attenuated below controls only with >6 h 50 µM Cd2+, yet augmented by up to 1.5- and 1.2-fold, respectively, by 10 µM Cd2+. Moreover, 10 µM, but not 25–50 µM Cd2+, caused 1.7-fold increase in superoxide anion (O2•−), detected by dihydroethidium, paralled by loss in cell viability, that was abolished by Tempol, MnTBAP, α-tocopherol and SOD1 or CAT overexpression. H2O2-generating NADPH oxidase 4 (NOX4) was attenuated by ~50% with 10 µM Cd2+ at 3 h compared to upregulation by 50 µM Cd2+ (~1.4-fold, 30 min), which was sustained for 24 h. In summary, O2•− predominates with low–moderate Cd2+, driving an adaptive response, whereas oxidative stress by elevated H2O2 at high Cd2+ triggers cell death signaling pathways.HighlightsDifferent levels of reactive oxygen species are generated, depending on cadmium concentration.Superoxide anion predominates and H2O2 is suppressed with low cadmium representing oxidative eustress.High cadmium fosters H2O2 by inhibiting catalase and increasing NOX4 leading to oxidative distress.Superoxide dismutase mimetics and overexpression were less effective with high versus low cadmium.Oxidative stress profile could dictate downstream signalling pathways.

Generation of oxidative stress in freshwater oligochaete Tubifex tubifex due to exposure to aniline: time and concentration dependent toxicity assessment

ABSTRACT Our current study examines the significant impact of aniline on the fish feed freshwater benthic annelid, Tubifex tubifex, including mortality, changes in total protein concentration and antioxidant enzyme activity (catalase, superoxide dismutase, glutathione-s transferase and glutathione peroxidase), as well as the generation of oxidative stress (by assessing malondialdehyde concentration). The 96-hour LC50 value of aniline is 276.940 mg/L. The General Unified Threshold Model of Survival (GUTS) was used to validate the survival rate pattern of the test organism in response to aniline at the acute level, with the GUTS-SD model better correctly predicting the expected course of population death. During long-term bioassay antioxidant enzymes activities (superoxide dismutase, glutathione-s transferase and glutathione peroxidase) and oxidative stress biomarkers concentration (malondialdehyde concentration) is substantially enhanced while protein concentration and Catalase activity are markedly reduced during the bioassay. The stress and detrimental effects of aniline on Tubifex tubifex were examined in the current study, taking into account all biomarkers, by utilising the Integrated Biomarker Response index. The results show that exposure to toxicants like aniline has a detrimental effect on Tubifex tubifex's survival rate and general health.

Formulation of lactoferrin decorated dextran based chitosan-coated europium metal-organic framework for targeted delivery of curcumin

Hepatocellular carcinoma (HPTC) currently ranks as the third leading cause of cancer-related mortality, necessitating an advanced formulation strategy. Recently, lactoferrin (Lf) has been utilized as a specific targeting ligand in HPTC due to its high specificity towards the asialoglycoprotein receptor expressed in cancer cells. Therefore, we present the fabrication of an Lf-decorated carboxymethyl dextran-encased chitosan-coated europium metal-organic framework-based nanobioconjugate (Lf-CMD-CS-CUR@Eu-MOF) for targeted curcumin (CUR) delivery. Briefly, CUR was loaded into Eu-MOF, followed by coating cationic ‘CS’ on the CUR@Eu-MOF surface. Simultaneously, Lf-decorated CMD was prepared via an esterification reaction. Subsequently, Lf-CMD-CS-CUR@Eu-MOF was synthesized using the Maillard reaction. Various spectral characterizations, drug entrapment, drug content, in vitro drug release, biocompatibility and cell cytotoxicity studies were performed. It exhibited an entrapment efficiency of 88.87 ± 2.1 %, a drug content of 3.45 ± 0.98 %, and a drug loading rate of 34.85 ± 0.6 mg/g. Furthermore, the Lf-CMD-CS-CUR@Eu-MOF exhibits excellent biocompatibility with normal cells. The in vitro dissolution study confirmed a release of 78.12 % of ‘CUR’ in pH 5.8 phosphate buffer (over 120 h), attributed to the controlled release rate by the ‘CS’ coating on the surface of CUR@Eu-MOF. The BEL-7402 cell line showed concentration-dependent toxicity of nanobioconjugate to cancerous cells. Therefore, when ‘Lf’ is surface-decorated onto an appropriate polymeric material, it gains the capability to function as a carrier for transporting ‘CUR’ to the precise target site within HPTC. In conclusion, Lf-CMD incorporated CS-coated Eu-MOF can provide a promising approach for targeted drug delivery in HPTC management.

Synthesis of Selenium Nanoparticles and Their Effect on Pancreatic Functions and Acute Pancreatitis in Rats.

Acute pancreatitis (AP) have been documented to have severe impact on pancreatic function. Frequent incidence of AP can result in chronic pancreatitis and thereby it can increase the probability of pancreatic cancers. This study intended to examine the effect of selenium nanoparticles (Se-NPs) synthesized from Coleus forskohlii leaf extract on pancreatic function and AP in rat. Primarily, Se-NPs was fabricated using the C. forskohlii leaf extract. The synthesized nanomaterial was characterized through UV-visible, XRD, and FTIR spectroscopies. Notably, the zeta potential of Se-NPs was found to be -32.8 mV with a polydispersity index (PDI) of 0.18. Morphological analysis on SEM unveiled the spherical shape of Se-NP with an average particle size of 12.69 nm. Strikingly, cytotoxicity analysis on pancreatic cancer and normal cells unveiled the concentration-dependent toxicity profile. However, IC 50 value is lower in normal pancreatic cell lines in comparison to pancreatic cancer cells lines. Assessment of Se-NPs on AP rats revealed the positive impact of Se-NPs. It effectively decreased the amount of lipase, amylase, IL-1β, MDA, NO, and Bcl-2 while increased the glucose, insulin, HOMA-β and antioxidant potential in AP rats. In addition, an evaluation of Se-NPs in the pancreatic functions revealed the non-harmful effect of Se-NPs.

Evaluating the in vitro developmental toxicity potency of a series of petroleum substance extracts using new approach methodologies (NAMs)

The present study evaluates the in vitro developmental toxicity and the possible underlying mode of action of DMSO extracts of a series of highly complex petroleum substances in the mouse embryonic stem cell test (mEST), the zebrafish embryotoxicity test (ZET) and the aryl hydrocarbon receptor reporter gene assay (AhR CALUX assay). Results show that two out of sixteen samples tested, both being poorly refined products that may contain a substantial amount of 3- to 7-ring polycyclic aromatic compounds (PACs), induced sustained AhR activation in the AhR CALUX assay, and concentration-dependent developmental toxicity in both mEST and ZET. The other samples tested, representing highly refined petroleum substances and petroleum-derived waxes (containing typically a very low amount or no PACs at all), were negative in all assays applied, pointing to their inability to induce developmental toxicity in vitro. The refining processes applied during the production of highly refined petroleum products, such as solvent extraction and hydrotreatment which focus on the removal of undesired constituents, including 3- to 7-ring PACs, abolish the in vitro developmental toxicity. In conclusion, the obtained results support the hypothesis that 3- to 7-ring PACs are the primary inducers of the developmental toxicity induced by some (i.e., poorly refined) petroleum substances and that the observed effect is partially AhR-mediated.

Aggregation and cytotoxicity of food additive dye (Azorubine)-albumin adducts: a multi-spectroscopic, microscopic and computational analysis

Protein and peptide misfolding is a central factor in the formation of pathological aggregates and fibrils linked to disorders like Alzheimer’s and Parkinson’s diseases. Therefore, it’s essential to understand how food additives, particularly Azorubine, affect protein structures and their ability to induce aggregation. In this study, human serum albumin (HSA) was used as a model protein to investigate the binding and conformational changes caused by azorubine, a common food and drink colorant. The research revealed that azorubine destabilized the conformation of HSA at both physiological (pH 7.4) and acidic (pH 3.5) conditions. The loss of tryptophan fluorescence in HSA suggested significant structural alterations, particularly around aromatic residues. Far UV-CD analysis demonstrated disruptions in HSA's secondary structure, with a notable reduction in α-helical structures at pH 7.4. At pH 3.5, Azorubine induced even more extensive perturbations, resulting in a random coil conformation at higher azorubine concentrations. The study also investigated aggregation phenomena through turbidity measurements, RLS analysis, and TEM imaging. At pH 3.5, larger insoluble aggregates formed, while at pH 7.4, only conformational changes occurred without aggregate formation. Cytotoxicity assessments on neuroblastoma (SH-SY5Y) cells highlighted the concentration-dependent toxicity of albumin aggregates. Molecular dynamics simulations reaffirmed the stable interaction between azorubine and HSA. This research provides valuable insights into the mechanisms by which azorubine influences protein conformations. To further advance our understanding and contribute to the broader knowledge in this area, several future directions can be considered such as exploring other proteins, studying dose-response relationship, gaining mechanistic insights, biological relevance, toxicity assessment, identifying alternative food colorants, and mitigation strategies to prevent adverse effects of azorubine on serum proteins.Communicated by Ramaswamy H. Sarma

Adsorption and removal of polystyrene nanoplastics from water by green-engineered clays

Human exposure to micro- and nanoplastics (MNPs) commonly occurs through the consumption of contaminated drinking water. Among these, polystyrene (PS) is well-characterized and is one of the most abundant MNPs, accounting for 10 % of total plastics. Previous studies have focused on carbonaceous materials to remove MNPs by filtration, but most of the work has involved microplastics since nanoplastics (NPs) are smaller in size and more difficult to measure and remove. To address this need, green-engineered chlorophyll-amended sodium and calcium montmorillonites (SMCH and CMCH) were tested for their ability to bind and detoxify parent and fluorescently labeled PSNP using in vitro, in silico, and in vivo assays. In vitro dosimetry, isothermal analyses, thermodynamics, and adsorption/desorption kinetic models demonstrated 1) high binding capacities (173–190 g/kg), 2) high affinities (103), and 3) chemisorption as suggested by low desorption (≤42 %) and high Gibbs free energy and enthalpy (>|−20| kJ/mol) in the Langmuir and pseudo-second-order models. Computational dynamics simulations for 30 and 40 monomeric units of PSNP depicted that chlorophyll amendments increased the binding percentage and contributed to the sustained binding. Also, 64 % of PSNP bind to both the head and tail of chlorophyll aggregates, rather than the head or tail only. Fluorescent PSNP at 100 nm and 30 nm that were exposed to Hydra vulgaris showed concentration-dependent toxicity at 20–100 µg/mL. Importantly, the inclusion of 0.05–0.3 % CMCH and SMCH significantly (p ≤ 0.01) and dose-dependently reduced PSNP toxicity in morphological changes and feeding rate. The bioassay validated the in vitro and in silico predictions about adsorption efficacy and mechanisms and suggested that CMCH and SMCH are efficacious binders for PSNP in water.

Alcohol induces ER stress and apoptosis by inducing oxidative stress and disruption of calcium homeostasis in glial cells

Alcohol has teratogenic effects that can cause developmental abnormalities and alter anatomical and functional characteristics of the developed brain and other organs. Glial cells play a crucial role in alcohol metabolism and protect neurons from toxic effects of alcohol. However, chronic alcohol exposure can lead to uncontrollable levels of reactive oxygen species, resulting in the death of glial cells and exposing neuronal cells to the toxic effects of alcohol. The exact molecular mechanism of alcohol-induced glial cell death has not been fully explored. This study reported that different concentrations of alcohol induce different expressions of ER stress markers in glial cells, focusing on the role of endoplasmic reticulum (ER) stress. Alcohol-induced concentration-dependent toxicity in both cells also induced oxidative stress, leading to mitochondrial damage. The expression of p53 and apoptotic proteins was significantly up-regulated after alcohol exposure, while Bcl2 (anti-apoptotic) was down-regulated. The signalling pathway for ER stress was activated and up-regulated marker proteins in a concentration-dependent manner. Cells pre-treated with BAPTA-AM and NAC showed significant resistance against alcohol assault compared to other cells. These in vitro findings will prove valuable for defining the mechanism by which alcohol modulates oxidative stress, mitochondrial and ER damage leading to glial cell death.

N-acetyl cysteine mitigates lung damage and inflammation after chlorine exposure in vivo and ex vivo

The objective of this study was to explore the effects of antioxidant treatments, specifically N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA), in a mouse model of chlorine (Cl2)-induced lung injury. Additionally, the study aimed to investigate the utility of pig precision-cut lung slices (PCLS) as an ex vivo alternative for studying the short-term effects of Cl2 exposure and evaluating antioxidant treatments.The toxicological responses were analyzed in Cl2-exposed mice (inflammation, airway hyperresponsiveness (AHR)) and PCLS (viability, cytotoxicity, inflammatory mediators). Airways contractions were assessed using a small ventilator for mice and electric-field stimulation (EFS) for PCLS. Antioxidant treatments were administered to evaluate their effects.In Cl2-exposed mice, NAC treatment did not alleviate AHR, but it did reduce the number of neutrophils in bronchoalveolar lavage fluid and inflammatory mediators in lung tissue. In PCLS, exposure to Cl2 resulted in concentration-dependent toxicity, impairing the lung tissue's ability to respond to EFS-stimulation. NAC treatment increased viability, mitigated the toxic responses caused by Cl2 exposure, and maintained contractility comparable to unexposed controls. Interestingly, NACA did not provide any additional treatment effect beyond NAC in both models.In conclusion, the establishment of a pig model for Cl2-induced lung damage supports further investigation of NAC as a potential treatment. However, the lack of protective effects on AHR after NAC treatment in mice suggests that NAC alone may not be sufficient as a complete treatment for Cl2 injuries. Optimization of existing medications with a polypharmacy approach may be more successful in addressing the complex sequelae of Cl2-induced lung injury.

Iron Oxide Nanoparticles with Supramolecular Ureido-Pyrimidinone Coating for Antimicrobial Peptide Delivery.

Antimicrobial peptides (AMPs) can kill bacteria by disrupting their cytoplasmic membrane, which reduces the tendency of antibacterial resistance compared to conventional antibiotics. Their possible toxicity to human cells, however, limits their applicability. The combination of magnetically controlled drug delivery and supramolecular engineering can help to reduce the dosage of AMPs, control the delivery, and improve their cytocompatibility. Lasioglossin III (LL) is a natural AMP form bee venom that is highly antimicrobial. Here, superparamagnetic iron oxide nanoparticles (IONs) with a supramolecular ureido-pyrimidinone (UPy) coating were investigated as a drug carrier for LL for a controlled delivery to a specific target. Binding to IONs can improve the antimicrobial activity of the peptide. Different transmission electron microscopy (TEM) techniques showed that the particles have a crystalline iron oxide core with a UPy shell and UPy fibers. Cytocompatibility and internalization experiments were carried out with two different cell types, phagocytic and nonphagocytic cells. The drug carrier system showed good cytocompatibility (>70%) with human kidney cells (HK-2) and concentration-dependent toxicity to macrophagic cells (THP-1). The particles were internalized by both cell types, giving them the potential for effective delivery of AMPs into mammalian cells. By self-assembly, the UPy-coated nanoparticles can bind UPy-functionalized LL (UPy-LL) highly efficiently (99%), leading to a drug loading of 0.68 g g-1. The binding of UPy-LL on the supramolecular nanoparticle system increased its antimicrobial activity against E. coli (MIC 3.53 µM to 1.77 µM) and improved its cytocompatible dosage for HK-2 cells from 5.40 µM to 10.6 µM. The system showed higher cytotoxicity (5.4 µM) to the macrophages. The high drug loading, efficient binding, enhanced antimicrobial behavior, and reduced cytotoxicity makes ION@UPy-NH2 an interesting drug carrier for AMPs. The combination with superparamagnetic IONs allows potential magnetically controlled drug delivery and reduced drug amount of the system to address intracellular infections or improve cancer treatment.