Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer’s disease mouse model

Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM2.5) exposure and Alzheimer’s disease (AD), the PM2.5-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM2.5 via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM2.5 for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM2.5 exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM2.5 induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM2.5 exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM2.5 subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM2.5 after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM2.5-mediated development of AD.

Effects of Lead and/or Cadmium on the Contractile Function of the Rat Myocardium Following Subchronic Exposure and Its Attenuation with a Complex of Bioprotectors

Background: As by-products of copper smelting, lead and cadmium pollute both workplace air at metallurgical plants and adjacent territories. Their increased levels in the human body pose a higher risk of cardiovascular diseases. The objective of our study was evaluate changes in the rat myocardium contractile function following moderate subchronic exposure to soluble lead and/or cadmium salts and its attenuation by means of a complex of bioprotectors. Materials and methods: The subchronic exposure of rats was modelled by intraperitoneal injections of 3-H2O lead acetate and/or 2.5-H2O cadmium chloride in single doses, 6.01 mg of Pb and 0.377 mg of Cd per kg of body weight, respectively, 3 times a week during 6 weeks. The myosin heavy chains isoform ratio was estimated by gel electrophoresis. Biomechanical measurements were performed on isolated multicellular preparations of the myocardium (trabeculae and papillary muscles) from the right ventricle. Results: The subchronic lead exposure slowed down the contraction and relaxation cycle and increased myosin expression towards slowly cycling V3 isomyosins. Cadmium intoxication, on the contrary, shortened the contraction and relaxation cycle and shifted the ratio of isomyosin forms towards rapidly cycling V1. Following the combined exposure to lead and cadmium, some contractile characteristics changed in the direction typical of the effect of lead while others – in that of cadmium. We observed that the metal combination either neutralized or enhanced the isolated damaging effect of each heavy metal. The use of a complex of bioprotectors normalized the myocardial contractility impaired by the exposure to lead and cadmium either partially or completely. Discussion: Despite the changes in myocardial contractility following the subchronic lead and cadmium exposure, the mechanisms of heterometric regulation were maintained. The adverse cardiotoxic effect of the combination of these industrial contaminants may be weakened by administering a complex of bioprotectors.