Phosphorus Localization and Its Involvement in the Formation of Concentrated Uranium in the Renal Proximal Tubules of Rats Exposed to Uranyl Acetate

Abstract

Although the kidneys comprise a critical target of uranium exposure, the dynamics of renal uranium distribution have remained obscure. Uranium is considered to function physiologically in the form of uranyl ions that have high affinity for phosphate groups. The present study applied microbeam-based elemental analysis to precisely determine the distribution of phosphorus and uranium in the kidneys of male Wistar rats exposed to uranium. One day after a single subcutaneous injection of uranyl acetate (2 mg/kg), areas of concentrated phosphorus were scattered in the S3 segments of the proximal tubule of the kidneys, whereas the S3 segments in control rats and in rats given a lower dose of uranium (0.5 mg/kg) contained phosphorus without concentrated phosphorus. Areas with concentrated phosphorus contained uranium 4- to 14-fold more than the mean uranium concentration (126–472 vs. 33.1 ± 4.6 μg/g). The chemical form of uranium in the concentrated phosphorus examined by XAFS was uranium (VI), suggesting that the interaction of uranyl ions with the phosphate groups of biomolecules could be involved in the formation of uranium concentration in the proximal tubules of kidneys in rats exposed to uranium.

Single-Cell Imaging for Studies of Renal Uranium Transport and Intracellular Behavior

“…Uranium colocalization with phosphorus and potassium was observed at the early stages of toxicity, even though uranium compounds precipitate in the cytoplasmic compartment in the form of uranyl phosphate needles after exposure to toxic concentrations (400-2000 μM) of uranium [35][36][37]. The reason for potassium and uranium colocalization cannot be clearly explained, but it has also been confirmed using in vivo systems in uranium-treated rat renal tubules [19]. Protein aggregation due to uranium-protein interaction may also be a reason for detection at the early phase of toxicity because uranyl ions have a high affinity for phosphate groups on biomolecules [38][39][40], even though the formation mechanism is not well understood.…”

“…Microbeam scanning elemental analysis, which is also known as μ-PIXE (particle-induced X-ray emission with microprobe) analysis, is one of the suitable analytical techniques for detecting the precise distribution of elements in a small specimen with good detection of light elements, such as phosphorus, potassium, and calcium. Our previous studies with animal experiments suggested the colocalization of uranium and the light elements in the renal tubules [19] albeit the positional relationship of these elements in the cell remains unclear. PIXE imaging of S3 cells may provide new insights into the implications of cellular uranium dynamics.…”

“…Uranium in these areas was partially reduced [18]. In addition, phosphorus and potassium were colocalized in some of these areas [19]. The formation mechanism of uranium bioconcentration is a key determinant of uranium toxicity because the remaining uranium can cause future deleterious effects.…”

Impact of Local High Doses of Radiation by Neutron Activated Mn Dioxide Powder in Rat Lungs: Protracted Pathologic Damage Initiated by Internal Exposure

“…Apoptosis was clearly evident in the bronchiole epithelium in the 56 Mn group at two months. Comparably, Homma et al have reported renal toxicity to uranium exposure in relation to uranium distribution and uranium-induced apoptosis in the kidneys [21][22][23].…”

Cytoplasmic aggregation of uranium in human dopaminergic cells after continuous exposure to soluble uranyl at non-cytotoxic concentrations

“…In osteosarcoma cells exposed to 300 µM uranyl, precipitates were identified as meta-autunite Ca[(UO2)(PO4)]2(H2O)11 by EXAFS (Pierrefite-Carle et al, 2017). Phosphorous and uranium were colocalized in renal proximal tubules from rats exposed to uranyl acetate as shown by micro-PIXE and micro-EXAFS (Homma-Takeda et al, 2019). In neuron-like cells exposed to 10 µM uranyl we did not observe phosphorous or calcium co-localization with uranium suggesting a different mechanism of aggregation.…”