Abstract
Animal studies show that exposure to the environmental pollutant 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) causes alterations in hepatic metals as measured in acid-digested volume-adjusted tissue. These studies lack the detail of the spatial distribution within the liver. Here we use X-ray fluorescence microscopy (XFM) to assess the spatial distribution of trace elements within liver tissue. Liver samples from male Sprague Dawley rats, treated either with vehicle or PCB126, were formalin fixed and paraffin embedded. Serial sections were prepared for traditional H&E staining or placed on silicon nitride windows for XFM. With XFM, metal gradients between the portal triad and the central vein were seen, especially with copper and iron. These gradients change with exposure to PCB126, even reverse. This is the first report of how micronutrients vary spatially within the liver and how they change in response to toxicant exposure. In addition, high concentrations of zinc clusters were discovered in the extracellular space. PCB126 treatment did not affect their presence, but did alter their elemental makeup suggesting a more general biological function. Further work is needed to properly evaluate the gradients and their alterations as well as classify the zinc clusters to determine their role in liver function and zinc homeostasis.
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Acknowledgements
This research was supported by funding from the NIH (P42 ES013661) and additional support from a KC Donnelly externship award supplement awarded to W. Klaren from the NIEHS and the Superfund Research program. This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. This work makes up a portion of the dissertation research of W. Klaren. All opinions provided are those of the authors and not those of any granting agency. The authors would like to thank Dr. Gregor Luthe for synthesizing the PCB126 and Dr. Hans-Joachim Lehmler for maintaining the PCB126 stock. In addition, the authors would like to recognize Dr. Katherine Gibson-Corley for her assistance and helpful discussions on the pathological findings. Finally, the authors greatly appreciate the help from fellow lab members throughout the study.
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The University of Iowa Institutional Animal Care and Use Committee approval was obtained for the animal study.
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Klaren, W.D., Vine, D., Vogt, S. et al. Spatial distribution of metals within the liver acinus and their perturbation by PCB126. Environ Sci Pollut Res 25, 16427–16433 (2018). https://doi.org/10.1007/s11356-017-0202-0
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DOI: https://doi.org/10.1007/s11356-017-0202-0