Jørgen Frøkiær

Tamoxifen attenuates development of lithium-induced nephrogenic diabetes insipidus in rats

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Stine Julie Tingskov
  • Shan Hu, Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Korea (South), Republic of.
  • ,
  • Jorgen Frøkiær
  • Tae-Hwan Kwon, Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Korea (South), Republic of.
  • ,
  • Weidong Wang, Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Korea (South), Republic of.
  • ,
  • Rikke Norregaard

Lithium is widely used in treatment of bipolar affective disorders, but often causes nephrogenic diabetes insipidus (NDI), a disorder characterized by severe urinary concentrating defects. Lithium-induced NDI is caused by lithium uptake by collecting duct principal cells and altered expression of aquaporin-2 (AQP2), which are essential for water reabsorption of tubular fluid in the collecting duct. Sex hormones have previously been shown to affect the regulation of AQP2, so we tested whether tamoxifen (TAM), a selective estrogen receptor modulator, would attenuate lithium-induced alterations on renal water homeostasis. Rats were treated for 14 days with lithium and TAM treatment was initiated one week after onset of lithium administration. Lithium treatment resulted in severe polyuria and reduced AQP2 expression, which was ameliorated by TAM. Consistent with this, TAM attenuated downregulation of AQP2 and increased phosphorylation of the cAMP responsive element binding protein (CREB), which induced AQP2 expression, in freshly isolated inner medullary collecting duct suspension prepared from lithium-treated rats. In conclusion, TAM attenuated dose-dependently polyuria, impaired urine concentration, and downregulation of AQP2 protein expression in rats with lithium-induced NDI. These findings suggest that TAM is likely to be a novel therapeutic option for lithium-induced NDI.

Original languageEnglish
JournalAmerican Journal of Physiology: Renal Physiology
Volume314
Issue5
Pages (from-to)F1020-F1025
Number of pages6
ISSN1931-857X
DOIs
Publication statusPublished - May 2018

    Research areas

  • Journal Article

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