CLINICAL AND EXPERIMENTAL JUSTIFICATION DEPLETED URANIUM BIOEFFECTS WHEN ITS INCORPORATED

The article presents the results of a comprehensive clinical and experimental study of the bioeffects of depleted uranium during its incorporation, with an emphasis on the cellular and molecular mechanisms of toxic action. In the course of a multidisciplinary study using modern methods of molecular biology and histopathology, key aspects of the cytotoxic effect of depleted uranium nanoparticles during its incorporation and bio-distribution of its nanoscale particles in the body were studied in detail. Special attention is paid to the mechanisms of inhalation incorporation of depleted uranium and the distribution of its particles in the body, taking into account potential target organs at the molecular and organ levels. In vivo methods have studied the effect of inhaled intake of nanoscale depleted uranium particles on the morphofunctional state of cells of critically important target organs: lung tissue with selective accumulation in alveolar macrophages and epithelial cells, kidneys, liver, and central nervous system. At the micromorphological level, it has been established that the persistence of depleted uranium nanoparticles in the body induces oxidative stress due to the generation of reactive oxygen species, which leads to DNA damage, impaired proliferation and induction of cell apoptosis, as well as mitochondrial dysfunction, which is confirmed by histopathological and biochemical markers. A fundamentally important aspect of the study was the identification of the key role of activation of proinflammatory signaling pathways in the pathogenesis of fibrotic and neoplastic changes under the influence of depleted uranium. The data obtained expand modern understanding of the cytopathogenetic mechanisms of depleted uranium action and can be used to develop biomonitoring methods and correct its negative effects.