Comprehensive analysis of renal arsenic accumulation using images based on X-ray fluorescence at the tissue, cellular, and subcellular levels

Abstract

Exposure to arsenic (As) through drinking water results in accumulation of As and its methylated metabolites in several organs, promoting adverse health effects, particularly potential development of cancer. Arsenic toxicity is a serious global health concern, since over 200 million people are chronically exposed worldwide, Abundant biochemical and epidemiological evidence indicates that the kidney is an important site of uptake and accumulation of As, and mitochondrial damage plays a crucial role in arsenic toxicity. However, non-destructive analyses and in situ images revealing As fate in renal cells and tissue are scarce or almost non-existent. In this work, kidney tissue from exposed rats was analyzed by EDXRF (Energy dispersive X-ray fluorescence), micro-SRXRF (micro X-ray Fluorescence using Synchrotron Radiation), SRTXRF (SRXRF in total reflection condition), SEM-EDX (Scanning Electron Microscope in combination with EDXRF) and SRXRF-XANES (SRXRF in combination with X-ray Absorption near Edge Spectroscopy). Our results provide evidence of renal cortex distribution of As with periglomerular localization, co-localization of S, Cu and As in subcellular compartment of proximal tubule cells, mono-methylarsonous acid accumulation in renal cortex mitochondria, and altered subcellular concentration and distribution of other elements.

Circulating Arsenic is Associated with Long-Term Risk of Graft Failure in Kidney Transplant Recipients: A Prospective Cohort Study

“…An increasing body of evidence supports that the kidney is a primary site of arsenic uptake and accumulation. Recently, X-ray fluorescence spectrometry allowed detection of arsenic accumulation, specifically at level of the kidney cortex [51]. X-ray fluorescence spectrometry may provide comprehensive information of bioaccumulation for biomedical and toxicological research by allowing direct measurement of the distribution of arsenic at tissue, cellular, and subcellular level.…”

“…Next, X-ray absorption spectroscopy has been shown to allow in vivo assessment of whole-body distribution, which is key information for the development of chelation therapies [52]. Future studies using these analytical methods may provide essential research data to understand the sequence of specific mechanisms of nephrotoxicity and deepen the understanding of the association between long-term arsenic exposure and kidney damage [51].…”

Potential of total‐reflection X‐ray spectrometry for multielement analysis of biological samples using dilution or suspension sample preparation techniques

“…In previous studies, we showed the potential of such a system for biological sample mappings. [18,19] Detailed features and analytical conditions are displayed in Table 2. Spectral data from EDXRF analysis were evaluated using the WinFTM software, version 6.35 linked to the instrument.…”

Subcellular Localization of Copper—Cellular Bioimaging with Focus on Neurological Disorders

“…Depending on the synchrotron beamline, imaging can be performed with lateral resolution down to 20 nm and, in case of XAS spectroscopy, down to 50 nm [103]. Typically, samples are analyzed at 50-100 µm sections [117,118,127]. Moreover, this technique offers the possibility to analyze the samples in hydrated state; therefore, no elaborated sample preparation such as resin embedding is required.…”