Matsushima Shuuichi, Tsuchiya Noriko, Fujisawa-Imura Kae, Fujisawa-Imura Kae, Hoshimoto Maruko, Takasu Nobuo, Torii Mikinori, Ozaki Kiyokazu, Narana Isao, Kotani Takao
Pathology Section, Drug Safety Evaluation, Developmental Research Laboratories, Shionogi & Co., Ltd, Toyonaka, Osaka 561-0825, Japan.
Toxicol Pathol. 2005;33(5):533-9. doi: 10.1080/01926230591034438.
Iron lactate was given to Sprague-Dawley rats intravenously at the dosage of 10 mg/kg/day and the early effects on the parathyroid gland were examined ultrastructurally along with the blood level of parathyroid hormone (PTH) after single, 3-day or 6-day administration. Blood levels of electrolytes and other parameters related to osteoclast dynamics were also measured by blood chemistry and histopathology. The plasma parathyroid hormone (PTH) level was elevated in the single and 3-day dosing group but was reduced in the 6-day dosing group. Histopathologically, an increase of osteoclasts in the primary spongiosa was observed in the 3- and 6-day dosing groups. Image analysis of the parathyroid gland revealed that the average area of the storage granule decreased during a experimental period, with the number of storage granules decreasing in the 3- and 6-day dosing group. The chief cells of the parathyroid gland were moderately atrophied in the 6-day dosing group. These results demonstrate that iron lactate immediately promotes discharge of PTH from the storage granules after the treatment and induces an increase of osteoclasts in the primary spongiosa. The findings collectively suggest a pathophysiological mechanism of iron lactate-induced osteopenia in rats.
以10毫克/千克/天的剂量给斯普拉格-道利大鼠静脉注射乳酸铁，在单次、3天或6天给药后，通过超微结构检查甲状旁腺的早期效应，并检测甲状旁腺激素（PTH）的血液水平。还通过血液化学和组织病理学测量了电解质的血液水平以及与破骨细胞动力学相关的其他参数。单次给药组和3天给药组的血浆甲状旁腺激素（PTH）水平升高，但6天给药组的血浆甲状旁腺激素水平降低。组织病理学检查显示，3天和6天给药组的初级海绵骨中破骨细胞增加。甲状旁腺的图像分析显示，在实验期间，储存颗粒的平均面积减小，3天和6天给药组的储存颗粒数量减少。6天给药组的甲状旁腺主细胞中度萎缩。这些结果表明，乳酸铁在治疗后立即促进储存颗粒中PTH的释放，并诱导初级海绵骨中破骨细胞增加。这些发现共同提示了大鼠乳酸铁诱导的骨质减少的病理生理机制。
