Biochemical and cellular effects of direct maxacalcitol injection into parathyroid gland in uremic rats

Kazuhiro Shiizaki, Shigeo Negi, Ikuji Hatamura, Toshifumi Sakaguchi, Fumie Saji, Ken Kunimoto, Masahide Mizobuchi, Ikuo Imazeki, Akira Ooshima, Tadao Akizawa

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

The most important etiological factors of resistance to medical treatments for secondary hyperparathyroidism are the decreased contents of the vitamin D receptor (VDR) and Ca-sensing receptor (CaSR) in parathyroid cells and a severely swollen parathyroid gland (PTG) as a result of hyperplasia. The effects of direct maxacalcitol (OCT) injection into PTG in terms of these factors were investigated in this study. The PTG of Sprague-Dawley rats that were 5/6 nephrectomized and fed a high-phosphate diet were treated by a direct injection of OCT (DI-OCT) or vehicle (DI-vehicle). The changes in serum intact parathyroid hormone (PTH), Ca2+, and phosphorus levels, in VDR and CaSR expression levels in parathyroid cells, and in Ca2+-PTH curves were examined. Apoptosis was analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and DNA electrophoresis for PTG. DI-OCT markedly decreased serum intact PTH level, and a significant difference in this level between DI-OCT and DI-vehicle was observed. However, serum Ca2+ and phosphorus levels did not changed markedly in both groups. The upregulations of both VDR and CaSR, the clear shift to the left downward in the Ca2+-PTH curve, and the induction of apoptosis after DI-OCT were observed. These findings were not observed in the DI-vehicle-treated rats. Moreover, these effects of DI-OCT were confirmed by the DI-OCT into one PTG and DI-vehicle alone into another PTG in the same rat. DI-OCT may introduce simultaneous VDR and CaSR upregulations and the regression of hyperplastic PTG, and these effects may provide a strategy for strongly suppressing PTH levels in very severe secondary hyperparathyroidism.

Original languageEnglish (US)
Pages (from-to)97-108
Number of pages12
JournalJournal of the American Society of Nephrology
Volume16
Issue number1
DOIs
StatePublished - 2005

ASJC Scopus subject areas

  • Nephrology

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