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Title of Journal: Pflugers Arch Eur J Physiol

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Abbravation: Pflügers Archiv - European Journal of Physiology

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Springer Berlin Heidelberg

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DOI

10.1007/bf00314872

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1432-2013

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Regulation of mineral metabolism by lithium

Authors: Hajar Fakhri Ganesh Pathare Abul Fajol Bingbing Zhang Thomas Bock Reinhard Kandolf Erwin Schleicher Jürg Biber Michael Föller Undine E Lang Florian Lang
Publish Date: 2013/09/07
Volume: 466, Issue: 3, Pages: 467-475
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Abstract

Lithium an inhibitor of glycogen synthase kinase 3 GSK3 is widely used for the treatment of mood disorders Side effects of lithium include nephrogenic diabetes insipidus leading to renal water loss Dehydration has in turn been shown to downregulate Klotho which is required as coreceptor for the downregulation of 125OH2D3 formation by fibroblast growth factor 23 FGF23 FGF23 decreases and 125OH2D3 stimulates renal tubular phosphate reabsorption The present study explored whether lithium influences renal Klotho expression FGF23 serum levels 125OH2D3 formation and renal phosphate excretion To this end mice were analyzed after a 14day period of sham treatment or of treatment with lithium 200 mg/kg/day subcutaneously Serum antidiuretic hormone ADH FGF23 and 125OH2D3 concentrations were determined by ELISA or EIA renal Klotho protein abundance and GSK3 phosphorylation were analyzed by Western blotting and serum phosphate and calcium concentration by photometry Lithium treatment significantly increased renal GSK3 phosphorylation enhanced serum ADH and FGF23 concentrations downregulated renal Klotho expression stimulated renal calcium and phosphate excretion and decreased serum 125OH2D3 and phosphate concentrations In conclusion lithium treatment upregulates FGF23 formation an effect paralleled by substantial decrease of serum 125OH2D3 and phosphate concentrations and thus possibly affecting tissue calcification

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