Journal of Applied Toxicology

Silver nanoparticles (AgNPs) have emerged as an important class of nanomaterials for a wide range of applications. However, the unique properties of AgNPs could potentially lead to unexpected hazards to human and environmental health. In this study, a number of previous studies are summarized that demonstrate oxidative stress-, genotoxicity- and apoptosis-related changes brought about by AgNPs. The physicochemical properties of AgNPs that are involved in encouraging such changes are also discussed.

Neonates were injected (days 1–14) with benzo(a)pyrene, benz(a)anthracene or benzo(k)fluoranthene and killed on day 23. Exposure to benzo(a)pyrene or benz(a)anthracene increased the number of nonatretic antral follicles and the thecal layer thickness. Disturbed primordial oocytes were only observed after exposure to benzo(a)pyrene. Alterations in ovarian ERβ expression were detected. The response of the ovaries to estradiol in rats exposed to PAHs was suppressed. The study showed that postnatal exposure to PAHs disturbed development of the ovaries and caused ovarian dysfunction.

We developed methods for evaluating inhibitory potential of eight human cytochrome P450 isoforms using substrate cocktail, human liver microsomes and liquid chromatography/tandem mass spectrometry. Our methods can distinguish between a direct inhibition and a metabolism-dependent inhibition (MDI) based on shift of IC50 values following preincubation with tested compound and NADPH. These CYP inhibition assays are considered to be useful tools for evaluating both direct inhibition and MDI at an early stage of the drug discovery and development process.

The metabolic activation of polycyclic aromatic hydrocarbons (PAH) within air pollution particulate matter (PM_2.5) and PAH-DNA bulky stable adducts in human alveolar macrophage (AM) and/or human lung epithelial L132 cells in mono- and/or in cocultures were studied. Taken together, our relevant results support the exertion of genotoxicity of highly reactive PAH-derived metabolites produced within human AM not only in primary target human AM, but also in secondary target L132 cells.

The direct effect of palytoxin (PTX) on PC12 cells was examined as a model experiment for investigating its neurotoxic action. PTX reduced the cell viability, and this reduction was not significantly altered by antioxidants. PTX failed to cause the chromatin condensation and the DNA fragmentation, while caused the positive staining of the cell cytoplasm with propidium iodide and the release of lactate dehydrogenase into the medium. PTX may disrupt the plasma membranes, causing the non-oxidative necrotic cell death.

Apocynin, which is used as a specific NADPH oxidase inhibitor, has a preventive effect for intracellular ROS generation. An in vivo study of transgenic zebrafish (Brn3C: EGFP) was used to investigate the protective effects of apocynin on cisplatin-induced hair cell death. In an in vitro study, apocynin appeared to protect against cisplatin-induced apoptotic features on Hoechst 33258 staining in the HEI-OC1 cells. Apocynin has antioxidative effects and prevents cisplatin induced apoptotic cell death in HEI-OC1 cells as well as in zebrafish.

An integrated metabonomic approach, based on high-resolution ¹H NMR spectroscopy, was applied to find acute biochemical effects of NiCl₂ on renal tissues of rats. The metabolite changes corresponding to nickel exposure are related to amino acids, osmolytes and energy metabolites. Differential responses were observed in ¹H NMR spectra of these metabolites with exposure to low and high doses of NiCl₂. The present study shows a huge potential of metabonomics for mapping organ-based metabolic response during heavy metal toxicity.

The relationship of blood lead level (BLL) and blood cadmium level (BCL) with hematological and oxidative stress parameters was evaluated in exposed workers (50 painters and 23 battery workers) and control subjects (36). The changes in oxidative stress and hematological parameters were distinctively associated with either BLL or BCL. Thioredoxin reductase activity was not changed in the exposed workers. However, biochemical and hematological changes at low BLLs underlie the necessity of reevaluating the recommended health-based limits in occupational exposure to this metal.

We conducted a cytotoxic and genotoxic study in PG100 cell line and human lymphocytes after treatment with artemether. Using MTT assay, comet assay and ethidium bromide/acridine orange viability staining, we showed that artemether has a cytotoxic effect and induces necrosis in the PG100 gastric cancer cell line. However, its use as a possible antineoplastic drug is not recommended, since the cytotoxic effects were more consistent in human lymphocytes.