Eva Rollerova

The growing production of nanomaterials and their presence in consumer products raises fear about their impact on human health and the environment. Of particular concern are those nanomaterials that exhibit poor excretion and tend to accumulate in living organisms. Our study investigated the potential adverse biological effects of residual gold and titania nanoparticles (PEG-AuNPs and TiO₂NPs) 28 days after a single intravenous administration in rats. To comprehensively assess the potential health hazard of these metal nanoparticles (MNP), toxicological and transcriptomic analyses were employed. The liver was the primary organ of the MNP deposition, causing a reduction in the relative liver weight compared to unexposed animals. Concurrently, changes in serum biomarkers indicative of hepatic dysfunction and hematological and immunological alternations were determined. Integrated transcriptomic analysis unveiled exposure-induced effects on the rats' lungs, liver, and kidneys. The hepatic tissue, particularly in PEG-AuNPs-exposed rats, exhibited a noteworthy prevalence of deregulated genes, with functional classification spanning lipid metabolism, cell cycle, and cell proliferation pathways. Although the number of deregulated miRNAs was relatively modest compared to mRNA expression changes, both types of MNPs deregulated miR-203a, associated with liver injury, and miR-18a-5p and miR-32-5p linked to kidney damage. This study underscores the imperative for a more exhaustive biosafety assessment of poorly soluble MNPs that tend to deposit in the body. Such investigations are crucial for delineating the potential risks of these nanomaterials and guiding the development of adequate safety measures in their production and usage.

Titanium dioxide nanoparticles (TiO₂ NPs) are used in a wide range of applications. Although inhalation of NPs is one of the most important toxicologically relevant routes, experimental studies on potential harmful effects of TiO₂ NPs using a whole-body inhalation chamber model are rare. In this study, the profile of lymphocyte markers, functional immunoassays, and antioxidant defense markers were analyzed to evaluate the potential adverse effects of seven-week inhalation exposure to two different concentrations of TiO₂ NPs (0.00167 and 0.1308 mg TiO₂/m³) in mice. A dose-dependent effect of TiO₂ NPs on innate immunity was evident in the form of stimulated phagocytic activity of monocytes in low-dose mice and suppressed secretory function of monocytes (IL-18) in high-dose animals. The effect of TiO₂ NPs on adaptive immunity, manifested in the spleen by a decrease in the percentage of T-cells, a reduction in T-helper cells, and a dose-dependent decrease in lymphocyte cytokine production, may indicate immunosuppression in exposed mice. The dose-dependent increase in GSH concentration and GSH/GSSG ratio in whole blood demonstrated stimulated antioxidant defense against oxidative stress induced by TiO₂ NP exposure.

Despite the obvious advantages of gold nanoparticles for biomedical applications, controversial and incomplete toxicological data hamper their widespread use. Here, we present the results from an in vivo toxicity study using gold nanoparticles coated with polyethylene glycol (PEG-AuNPs). The pharmacokinetics and biodistribution of PEG-AuNPs were examined in the rat’s liver, lung, spleen, and kidney after a single i.v. injection (0.7 mg/kg) at different time intervals. PEG-AuNPs had a relatively long blood circulation time and accumulated primarily in the liver and spleen, where they remained for up to 28 days after administration. Increased cytoplasmic vacuolation in hepatocytes 24 h and 7 days after PEG-AuNPs exposure and apoptotic-like cells in white splenic pulp 24 h after administration has been detected, however, 28 days post-exposure were no longer observed. In contrast, at this time point, we identified significant changes in lipid metabolism, altered levels of liver injury markers, and elevated monocyte count, but without marked biological relevance. In blood cells, no DNA damage was present in any of the studied time intervals, with the exception of DNA breakage transiently detected in primary kidney cells 4 h post-injection. Our results indicate that the tissue accumulation of PEG-AuNPs might result in late toxic effects.

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Objectives: The purpose of this study was to evaluate the effects of neonatal exposure to the herbicide acetochlor (ACT) on pubertal development and reproductive functions in female Wistar rats and to investigate capability of ACT to interfere with estradiol binding to rat uterine estrogen receptors (ERs) ex vivo. Methods: Acetochlor (7.68 and 15.36 mg/kg/day) was administered by subcutaneous injection from postnatal day (PND) 4–7, and vaginal opening, and estrous cyclicity were evaluated from PND 8-159. A second group of adult ovariectomized female rats was dosed for 6 days with ACT (153.6 mg/kg/day, oral gavage). The interference of ACT with the binding of [³H]Estradiol -17β to uterine nuclear and cytoplasmic estrogen receptors was analyzed ex vivo in receptor binding assay. Results: Both doses of ACT caused acceleration of the age at eye opening and vaginal patency that were significantly different from the control. In addition, altered estrous cyclicity was observed in the ACT (15.36 mg/kg/day) group with 54% of the female rats displaying irregular cycles at PND 159. While uterine weights were not altered, a significant accumulation of uterine nuclear estrogen receptors was observed in the ACT group. Conclusion: These results indicate that acetochlor can act as the endocrine disruptor and that endpoints related to pubertal development and reproductive functions sensitive sites are targeted with this persistent pollutant.

Drug delivery to the central nervous system (CNS) represents one of the most priority challenges in research and development of pharmaceutical nanotechnology products. Among the various non-invasive approaches for CNS delivery, nanoparticle carriers and particularly polymeric nanoparticles (PNs) seem to be one of the most interesting. This review deals with PNs as CNS drug delivery systems and their potential endocrine disrupting properties. Possible interference with the development of neuroendocrine-reproductive system is considered. Special regard is being paid to potential mechanisms of PNs toxicity. Necessity to investigate the toxicity of nanomaterials and their impact on human health are discussed.