Toxic Kidney Damage in Rats Following Subchronic Intraperitoneal Exposure to Element Oxide Nanoparticles.

Chronic diseases of the urogenital tract, such as bladder cancer, prostate cancer, reproductive disorders, and nephropathies, can develop under the effects of chemical hazards in the working environment. In this respect, nanosized particles generated as by-products in many industrial processes seem to be particularly dangerous to organs such as the testes and the kidneys. Nephrotoxicity of element oxide particles has been studied in animal experiments with repeated intraperitoneal injections of Al2O3, TiO2, SiO2, PbO, CdO, CuO, and SeO nanoparticles (NPs) in total doses ranging from 4.5 to 45 mg/kg body weight of rats. NPs were synthesized by laser ablation. After cessation of exposure, we measured kidney weight and analyzed selected biochemical parameters in blood and urine, characterizing the state of the excretory system. We also examined histological sections of kidneys and estimated proportions of different cells in imprint smears of this organ. All element oxide NPs under investigation demonstrated a nephrotoxic effect following subchronic exposure. Following the exposure to SeO and SiO2 NPs, we observed a decrease in serum creatinine and urea, respectively. Exposure to Al2O3 NPs caused an increase in urinary creatinine and urea, while changes in total protein were controversial, as it increased under the effect of Al2O3 NPs and was reduced after exposure to CuO NPs. Histomorphological changes in kidneys are associated with desquamation of the epithelium (following the exposure to all NPs except those of Al2O3 and SiO2) and loss of the brush border (following the exposure to all NPs, except those of Al2O3, TiO2, and SiO2). The cytomorphological evaluation showed greater destruction of proximal sections of renal tubules. Compared to the controls, we observed statistically significant alterations in 42.1% (8 of 19) of parameters following the exposure to PbO, CuO, and SeO NPs in 21.1% (4 of 19)-following that, to CdO and Al2O3 NPs-and in 15.8% (3 of 19) and 10.5% (2 of 19) of indicators, following the exposure to TiO2 and SiO2 nanoparticles, respectively. Histomorphological changes in kidneys are associated with desquamation of epithelium and loss of the brush border. The cytomorphological evaluation showed greater destruction of proximal sections of renal tubules. The severity of cyto- and histological structural changes in kidneys depends on the chemical nature of NPs. These alterations are not always consistent with biochemical ones, thus impeding early clinical diagnosis of renal damage. Unambiguous ranking of the NPs examined by the degree of their nephrotoxicity is difficult. Additional studies are necessary to establish key indicators of the nephrotoxic effect, which can facilitate early diagnosis of occupational and nonoccupational nephropathies.

Subchronic systemic toxicity and bioaccumulation of Fe3O4 nano- and microparticles following repeated intraperitoneal administration to rats.

Aqueous suspensions of 10 nm, 50 nm, or 1 µm Fe(3)O(4) particles were injected intraperitoneally (ip) to rats at a dose of 500 mg/kg in 4 mL of sterile deionized water 3 times a week for 5 weeks. Following exposure, functional and biochemical indices and histopathological examinations of spleen and liver tissues of exposed rats were evaluated for signs of toxicity. The iron content of the blood was measured photometrically, and that of the liver and the spleen by atomic adsorption spectroscopy (AAS) and electron paramagnetic resonance (EPR) methods. It was found that, given equal mass doses, Fe(3)O(4) nanoparticles possess considerably higher systemic toxicity than microparticles, but within the nanometric range the relationship between particle size and resorptive toxicity is intricate and nonunique. The latter fact may be attributed to differences in different nanoparticles' toxicokinetics, which are controlled by both more or less substantial direct penetration of nanoparticles through biological barriers and their unequal solubility.

Some peculiarities of pulmonary clearance mechanisms in rats after intratracheal instillation of magnetite (Fe3O4) suspensions with different particle sizes in the nanometer and micrometer ranges: are we defenseless against nanoparticles?

We studied differences between phagocytic responses to nanoparticles (NPs) versus microparticles in the pulmonary region by synthesizing magnetite of different sizes and instilling suspensions of these particles intratracheally into rats' lungs. Ten and 50 nm particles caused a greater increase in cell counts of the bronchoalveolar lavage fluid (BALF) than the instillation of microparticles. The response to 10 nm particles was weaker than to 50 nm ones, and the smaller NPs were more cytotoxic; both were more cytotoxic than the microparticles. Phagocytic activity was also studied using optical and atomic force microscopy. Phagocytes were more "loaded" in the lungs instilled with 10 nm particles as compared with those instilled with 50 nm particles; NPs of both sizes were engulfed more avidly than microparticles. We found in a separate comparative experiment that magnetite NPs were more cytotoxic than titanium dioxide and quartz suspensions having particle size distribution typical of industrial dusts.

Prenatal and postnatal tobacco smoke exposure and respiratory health in Russian children.

BACKGROUND: Only few studies have assessed the relative impact of prenatal and postnatal exposure to tobacco smoke on the child's later asthma or chronic respiratory symptoms and to our knowledge no studies have elaborated respiratory infections and allergies in this context. OBJECTIVE: To assess the effects of prenatal and postnatal exposure to tobacco smoke on respiratory health of Russian school children. METHODS: We studied a population of 5951 children (8 to 12 years old) from 9 Russian cities, whose parents answered a questionnaire on their children's respiratory health, home environment, and housing characteristics. The main health outcomes were asthma, allergies, chronic respiratory symptoms, chronic bronchitis, and upper respiratory infections. We used adjusted odds ratios (ORs) from logistic regression analyses as measures of effect. RESULTS: Prenatal exposure due to maternal smoking had the strongest effects on asthma (adjusted OR 2.46, 95% CI 1.19-5.08), chronic bronchitis (adjusted OR 1.45, 95% CI 1.08-1.96) and respiratory symptoms, such as wheezing (adjusted OR 1.30, 95% CI 0.90-1.89). The associations were weaker for exposure during early-life (adjusted ORs 1.38/1.27/1.15 respectively) and after 2 years of age (adjusted ORs 1.45/1.34/1.18) compared to prenatal exposure and the weakest or non-existent for current exposure (adjusted ORs 1.05/1.09/1.06). Upper respiratory infections were associated more strongly with early-life exposure (adjusted OR 1.25, 95% CI 1.09-1.42) than with prenatal (adjusted OR 0.74, 95% CI 0.54-1.01) or current exposure (adjusted OR1.05, 95% CI 0.92-1.20). The risk of allergies was also related to early life exposure to tobacco smoke (adjusted OR 1.26, 95% CI 1.13-1.42). CONCLUSION: Adverse effects of tobacco smoke on asthma, chronic bronchitis, and chronic respiratory symptoms are strongest when smoking takes place during pregnancy. The relations are weaker for exposure during early-life and after 2 years of age and weakest or non-existent for current exposure.