PuSH - Publikationsserver des Helmholtz Zentrums München: Spatial investigation of the elemental distribution in Wilson's disease liver after D-penicillamine treatment by LA-ICP-MS.

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Hachmöller, O.* ; Zibert, A.* ; Zischka, H. ; Sperling, M.* ; Groba, S.R.* ; Grünewald, I.* ; Wardelmann, E.* ; Schmidt, H.H.J.* ; Hartmut, H.J.* ; Karst, U.*

Spatial investigation of the elemental distribution in Wilson's disease liver after D-penicillamine treatment by LA-ICP-MS.

J. Trace Elem. Med. Biol. 44, 26-31 (2017)

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At present, the copper chelator D-penicillamine (DPA) is the first-line therapy of Wilson's disease (WD), which is characterized by an excessive copper overload. Lifelong DPA treatments aim to reduce the amount of detrimental excess copper retention in the liver and other organs. Although DPA shows beneficial effect in many patients, it may cause severe adverse effects. Despite several years of copper chelation therapy, discontinuation of DPA therapy can be linked to a rapidly progressing liver failure, indicating a high residual liver copper load. In order to investigate the spatial distribution of remaining copper and additional elements, such as zinc and iron, in rat and human liver samples after DPA treatment, a high resolution (spotsize of 10 μm) laser ablation-inductively coupled plasma-mass spectrometry (LA‐ICP‐MS) imaging method was applied. Untreated LPP‐/− rats, an established animal model for WD, appeared with a high overall copper concentration and a copper distribution of hotspots distributed over the liver tissue. In contrast, a low (>2-fold decreased) overall copper concentration was detected in liver of DPA treated animals. Importantly, however, copper distribution was highly inhomogeneous with lowest concentrations in direct proximity to blood vessels, as observed using novel zonal analysis. A human liver needle biopsy of a DPA treated WD patient substantiated the finding of an inhomogeneous copper deposition upon chelation therapy. In contrast, comparatively homogenous distributions of zinc and iron were observed. Our study indicates that a high resolution LA‐ICP‐MS analysis of liver samples is excellently suited to follow efficacy of chelator therapy in WD patients.

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