title: Biochemical and cellular effects of direct maxacalcitol injection into parathyroid gland in uremic rats.
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), Ca(2+), and phosphorus levels, in VDR and CaSR expression levels in parathyroid cells, and in Ca(2+)-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 Ca(2+) 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 Ca(2+)-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.
authors.affiliation: Center of Blood Purification Therapy, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan. shiizaki@wakayama-med.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiizaki
authors.forename: Shigeo
authors.initials: S
authors.lastname: Negi
authors.forename: Ikuji
authors.initials: I
authors.lastname: Hatamura
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Fumie
authors.initials: F
authors.lastname: Saji
authors.forename: Ken
authors.initials: K
authors.lastname: Kunimoto
authors.forename: Masahide
authors.initials: M
authors.lastname: Mizobuchi
authors.forename: Ikuo
authors.initials: I
authors.lastname: Imazeki
authors.forename: Akira
authors.initials: A
authors.lastname: Ooshima
authors.forename: Tadao
authors.initials: T
authors.lastname: Akizawa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000473:pathology; D015552:Injections, Intralesional; D008297:Male; D010280:Parathyroid Glands / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000235:genetics; D044169:Receptors, Calcium-Sensing / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014511:Uremia / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D002117:Calcitriol; C051883:maxacalcitol; D002118:Calcium