Copper and Trace Elements in Gallbladder form Patients with Wilson's Disease Imaged and Determined by Synchrotron X-ray Fluorescence.

Wolf Osterode,Fritz Wrba,Gerald Falkenberg

doi:10.3390/jimaging7120261

Wolf Osterode, Fritz Wrba + Show 1 more

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https://doi.org/10.3390/jimaging7120261

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Abstract

Investigations about suspected tissue alterations and the role of gallbladder in Wilson’s disease (WD)—an inherited genetic disease with impaired copper metabolism—are rare. Therefore, tissue from patients with genetically characterised WD was investigated by microscopic synchrotron X-ray fluorescence (µSRXRF). For two-dimensional imaging and quantification of elements, X-ray spectra were peak-fitted, and the net peak intensities were normalised to the intensity of the incoming monochromatic beam intensity. Concentrations were calculated by fundamental parameter-based program quant and external standardisation. Copper (Cu), zinc (Zn) and iron (Fe) along with sulphur (S) and phosphorus (P) mappings could be demonstrated in a near histological resolution. All these elements were increased compared to gallbladder tissue from controls. Cu and Zn and Fe in WD-GB were mostly found to be enhanced in the epithelium. We documented a significant linear relationship with Cu, Zn and sulphur. Concentrations of Cu/Zn were roughly 1:1 while S/Cu was about 100:1, depending on the selected areas for investigation. The significant linear relationship with Cu, Zn and sulphur let us assume that metallothioneins, which are sulphur-rich proteins, are increased too. Our data let us suggest that the WD gallbladder is the first in the gastrointestinal tract to reabsorb metals to prevent oxidative damage caused by metal toxicity.

Highlights

Wilson’s disease (WD) is an inherited genetic disease with an impaired hepatic copper transport due to mutation in ATP7B which encodes the copper–transporting P-type ATPase leading to Cu accumulation in liver and extrahepatic organs [1,2,3]
Since the major route for the excretion of copper and other trace elements is via the bile, it was early questioned whether the imbalance of copper metabolism in WD
Demographicand andhistological histologicaldata dataare areshown shownfor forcontrol controlgallbladder gallbladder(C-GB)

Summary

Introduction

Wilson’s disease (WD) is an inherited genetic disease with an impaired hepatic copper transport due to mutation in ATP7B which encodes the copper–transporting P-type ATPase leading to Cu accumulation in liver and extrahepatic organs [1,2,3]. Trace elements such as copper and zinc play an essential role in balancing cell metabolism. Depending on one another they are components of many metalloproteins/metalloenzymes. Acute gallbladder hydrops or cholecystolithiasis have been described in WD and have been assumed to be causative for an unbalanced Cu metabolism [12,13,14,15,16]

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