Highly concentrated calcitriol and its analogues induce apoptosis of parathyroid cells and regression of the hyperplastic gland - Study in rats

Kazuhiro Shiizaki, Ikuji Hatamura, Shigeo Negi, Toshifumi Sakaguchi, Fumie Saji, Ikuo Imazeki, Eiji Kusano, Takashi Shigematsu, Tadao Akizawa

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11 Scopus citations

Abstract

Background. Controlling hyperplasia of the parathyroid gland (PTG) is important in the management of secondary hyperparathyroidism (SHPT). Regression of the hyperplastic PTG requires a decrease in the number of parathyroid cells (PTCs), so the present study investigated cell death caused by toxic agents or by clinically usable vitamin D metabolites. Methods. The PTGs of Sprague-Dawley rats, which had been 5/6-nephrectomized and fed a high-phosphate diet for 12 weeks, were treated with two consecutive direct injections (DI) of calcitriol, maxacalcitol, paricalcitol, doxercalciferol or phosphate-buffered saline containing either 0.01% or 90% ethanol (0.01-ET or 90-ET, respectively). Laboratory data, including serum levels of intact parathyroid hormone (intact-PTH), were obtained before and after the treatments. The PTGs were excised 24 h after the final injection and evaluated for PTC apoptosis using light and electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) method and DNA electrophoresis. Results. Treatment with any of the vitamin D metabolites and 90-ET significantly decreased the serum intact-PTH level, but only the latter significantly decreased the serum Ca level. Either treatment markedly increased the number of TUNEL-positive PTCs, but not in PTG treated with 0.01-ET. In PTGs treated with DI of any vitamin D metabolites was there ladder formation on DNA electrophoresis, as well as the characteristic morphological features of apoptosis in both the light and electron microscopic studies. Conclusions. DI of vitamin D metabolites may be effective in controlling not only the PTH level, but also PTG hyperplasia, in advanced SHPT by, at least in part, apoptosis-induced cell death. Our study was performed in rats.

Original languageEnglish (US)
Pages (from-to)1529-1536
Number of pages8
JournalNephrology Dialysis Transplantation
Volume23
Issue number5
DOIs
StatePublished - May 1 2008

Keywords

  • Cell death
  • Electron microscopy
  • Hyperparathyroidism
  • Renal osteodystrophy
  • Vitamin D

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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    Shiizaki, K., Hatamura, I., Negi, S., Sakaguchi, T., Saji, F., Imazeki, I., Kusano, E., Shigematsu, T., & Akizawa, T. (2008). Highly concentrated calcitriol and its analogues induce apoptosis of parathyroid cells and regression of the hyperplastic gland - Study in rats. Nephrology Dialysis Transplantation, 23(5), 1529-1536. https://doi.org/10.1093/ndt/gfm850