Optimization of dosing schedule of daily inhalant dexamethasone to minimize phase shifting of clock gene expression rhythm in the lungs of the asthma mouse model

Naomi Hayasaka, Tsuyoshi Yaita, Tomoyuki Kuwaki, Sato Honma, Ken Ichi Honma, Takashi Kudo, Shigenobu Shibata*

*この研究の対応する著者

研究成果: Article査読

38 被引用数 (Scopus)

抄録

Glucocorticoid receptor agonists such as dexamethasone (DEXA) have been recommended for the treatment of asthma. Anincreased frequency of dosing with these drugs seems preferable for cases of severe or uncontrolled asthma. The purpose of this experiment was to find the appropriate dosing schedule (frequency and timing) for DEXA inhalation based on chronotherapeutic dosing to minimize phase shifts of clock function in the lungs of the ovalbumin-treated asthmatic mouse. The daily rhythm of clock gene expression was similar between control and ovalbumin-treated mice. Acute inhalation of DEXA significantly increased mPer1 gene expression in the lungs but not the liver of mice. Daily exposure of DEXA at zeitgeber time 0 (lights on) or at zeitgeber time 18 (6 h after lights off) for 6 d caused a phase advance or phase delay of bioluminescence rhythm in the lungs, respectively, similar to light-induced phase shifts in locomotor activity rhythm. Daily zeitgeber time 0 exposure to DEXA attenuated the expression level of the mClca3 gene, which is associated with mucus overproduction, and there was a phase-advancing peak time of the mClca3 rhythm. The present results denote the importance of selecting the most appropriate time of day for nebulizer administration of DEXA to minimize adverse effects such as the phase shifting of clock function in asthmatic lungs. This is the first report of a successful protocol that could obtain phase shifts of clock gene expression rhythm in isolated peripheral organs in vivo.

本文言語English
ページ(範囲)3316-3326
ページ数11
ジャーナルEndocrinology
148
7
DOI
出版ステータスPublished - 2007 7月

ASJC Scopus subject areas

  • 内分泌学

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