Lipidomics Analysis Unravels Aberrant Lipid Species and Pathways Induced by Zinc Oxide Nanoparticles in Kidney Cells.

Zinc oxide nanoparticles (ZnO NPs) are widely used in versatile applications, from high technology to household products. While numerous studies have examined the toxic gene profile of ZnO NPs across various tissues, the specific lipid species associated with adverse effects and potential biomarkers remain elusive. In this study, we conducted a liquid chromatography-mass spectrometry based lipidomics analysis to uncover potential lipid biomarkers in human kidney cells following treatment with ZnO NPs. Furthermore, we employed lipid pathway enrichment analysis (LIPEA) to elucidate altered lipid-related signaling pathways. Our results demonstrate that ZnO NPs induce cytotoxicity in renal epithelial cells and modulate lipid species; we identified 64 lipids with a fold change (FC) > 2 and p < 0.01 with corrected p < 0.05 in HK2 cells post-treatment with ZnO NPs. Notably, the altered lipids between control HK2 cells and those treated with ZnO NPs were associated with the sphingolipid, autophagy, and glycerophospholipid pathways. This study unveils novel potential lipid biomarkers of ZnO NP nanotoxicity, representing the first lipidomic profiling of ZnO NPs in human renal epithelial cells.

Zinc oxide nanoparticles trigger autophagy-mediated cell death through activating lysosomal TRPML1 in normal kidney cells.

Zinc oxide nanoparticles (ZnO NPs) have been widely used in various materials including sunscreens, cosmetics, over-the-counter topical skin products, and pigments. As traces of the used ZnO NPs have been found in the kidney, it is crucial to uncover their potential risks. The aim of this study is to elucidate detrimental effects of ZnO NPs and the molecular mechanism behind their renal toxicity. Cytotoxic effects were measured by MTT assay after HK2 cells were exposed to ZnO NPs for 24 h and IC50 value was determined. ROS and intracellular Zn2+ levels were detected by flow cytometry, and localization of Zn2+ and lysosome was determined by confocal microscopy. Occurrence of autophagy and detection of autophagic flux were determined by Western blot and confocal microscopy, respectively. We performed unpaired student t test for two groups, and one-way ANOVA with Tukey's post hoc for over three groups. ZnO NPs induced cell death in human renal proximal tubule epithelial cells, HK2. Cytosolic Zn2+ caused autophagy-mediated cell death rather than apoptosis. Cytosolic Zn2+ processed in lysosome was released by TRPML1, and inhibition of TRPML1 significantly decreased autophagic flux and cell death. The findings of this study suggest that ZnO NPs strongly induce autophagy-mediated cell death in human kidney cells. Controlling TRPML1 can be potentially used to prevent the kidney from ZnO NPs-induced toxicity.

Quantitative evaluation of polyethersulfone and polytetrafluoroethylene membrane sorption in a polar organic chemical integrative sampler (POCIS).

The lag effect in the polar organic chemical integrative sampler (POCIS) equipped with a polyethersulfone (PES) membrane (POCIS-PES) is a potential limitation for its application in water environments. In this study, a POCIS with a poly(tetrafluoroethylene) (PTFE) membrane (POCIS-PTFE) was investigated for circumventing membrane sorption in order to provide more reliable concentration measurements of organic contaminants. Sampler characteristics such as sampling rates (RS) and sampler-water partition coefficients (KSW) were similar for POCIS-PES and POCIS-PTFE, indicating that partitioning into Oasis HLB as the receiving phase dominates the overall partitioning from the aqueous phase to the POCIS. Membrane sorption was quantified in both laboratory and field experiments. Although POCIS-PTFE showed minor membrane sorption, the PTFE membranes were not robust enough to prevent changes in the sorption of the pollutants to the inner Oasis HLB sorbent due to biofouling. This was reflected in significant ionization effects in the electrospray ionization (ESI) source during the LC-MS/MS analysis. Despite clear differences in the ionization effects, the two POCISs types provided similar time-weighted average (CTWA) concentrations after a two-week passive sampling campaign in surface water and the outflow of a wastewater treatment plant. This study contributes to a more detailed understanding of POCIS application by providing a quantitative evaluation of membrane sorption and its associated effects in the laboratory and field.

Comparing passive dosing and solvent spiking methods to determine the acute toxic effect of pentachlorophenol on Daphnia magna.

Pentachlorophenol (PCP) is a widespread and persistent hydrophobic organic pollutant in the environment despite its restricted public use. Risk assessment of such hydrophobic organic compounds (HOCs) is challenging because sorption and volatilization issues during toxicity test often lead to inconsistent exposure concentration. Considering the hydrophobicity of the PCP, in this study, a passive dosing format was applied by adopting a silicone O-ring as a reservoir and evaluated its applicability on the determination of PCP on Daphnia magna. Results obtained with passive dosing method were compared with that of solvent spiking method. We hypothesized that the passive dosing method may provide more reliable and accurate toxicity results than conventional solvent spiking approach. As a result, the partition coefficient of PCP between methanol and a test medium (log KMeOH:ISO) was 2.1, which enabled the maintenance of reliable exposure concentration throughout the experiment. In the acute toxicity tests, passive dosing and solvent spiking showed similar EC50 values of 576 and 485 µg/L for 24 h, and 362 and 374 µg/L for 48 h, respectively, which overlap with EC50 values of previous studies. Altogether, both methods were suitable for the acute toxicity assessment of hydrophobic PCP.

In Silico Modeling Method for Computational Aquatic Toxicology of Endocrine Disruptors: A Software-Based Approach Using QSAR Toolbox.

Computational analyses of toxicological processes enables high-throughput screening of chemical substances and prediction of their endpoints in biological systems. In particular, quantitative structure-activity relationship (QSAR) models have been increasingly applied to assess the environmental effects of a plethora of toxic materials. In recent years, some more highlighted types of toxicants are endocrine disruptors (EDs, which are chemicals that can interfere with any hormone-related metabolism). Because EDs may significantly affect animal development and reproduction, rapidly predicting the adverse effects of EDs using in silico techniques is required. This study presents an in silico method to generate prediction data on the effects of representative EDs in aquatic vertebrates, particularly fish species. The protocol describes an example utilizing the automated workflow of the QSAR Toolbox software developed by the Organization for Economic Co-operation and Development (OECD) to enable acute ecotoxicity predictions of EDs. As a result, the following are determined: (1) calculation of the numerical correlations between the concentration for 50% of lethality (LC50) and octanol-water partition coefficient (Kow), (2) output performances in which the LC50 values determined in experiments are compared to those generated by computations, and (3) the dependence of estrogen receptor binding affinity on the relationship between Kow and LC50.

An Eco-Safety Assessment of Glyoxal-Containing Cellulose Ether on Freeze-Dried Microbial Strain, Cyanobacteria, Daphnia, and Zebrafish.

The objective of this study was to investigate the aquatic-toxic effects of glyoxal-containing cellulose ether with four different glyoxal concentrations (0%, 1.4%, 2.3%, and 6.3%) in response to global chemical regulations, e.g., European Union Classification, Labeling and Packaging (EU CLP). Toxicity tests of glyoxal-containing cellulose ether on 11 different microbial strains, Microcystis aeruginosa, Daphnia magna, and zebrafish embryos were designed as an initial stage of toxicity screening and performed in accordance with standardized toxicity test guidelines. Glyoxal-containing cellulose ether showed no significant toxic effects in the toxicity tests of the 11 freeze-dried microbial strains, Daphnia magna, and zebrafish embryos. Alternatively, 6.3% glyoxal-containing cellulose ether led to a more than 60% reduction in Microcystis aeruginosa growth after 7 days of exposure. Approximately 10% of the developmental abnormalities (e.g., bent spine) in zebrafish embryos were also observed in the group exposed to 6.3% glyoxal-containing cellulose ether after 6 days of exposure. These results show that 6.3% less glyoxal-containing cellulose ether has no acute toxic effects on aquatic organisms. However, 6.3% less glyoxal-containing cellulose ether may affect the health of aquatic organisms with long-term exposure. In order to better evaluate the eco-safety of cellulosic products containing glyoxal, further studies regarding the toxic effects of glyoxal-containing cellulose ether with long-term exposure are required. The results from this study allow us to evaluate the aquatic-toxic effects of glyoxal-containing cellulosic products, under EU chemical regulations, on the health of aquatic organisms.