Toxicologic Pathology

 

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Toxicologic Pathology, Vol. 33, No. 5, 533-539 (2005)
DOI: 10.1080/01926230591034438

Articles

Ultrastructural and Morphometrical Evaluation of the Parathyroid Gland in Iron-Lactate-Overloaded Rats

Shuuichi Matsushima1,2, Noriko Tsuchiya1, Kae Fujisawa-Imura1, Maruko Hoshimoto1, Nobuo Takasu1, Mikinori Torii1, Kiyokazu Ozaki2, Isao Narana2 and Takao Kotani3

1 Pathology Section, Drug Safety Evaluation, Developmental Research Laboratories, Shionogi & Co., Ltd., Toyonaka, Osaka 561-0825, Japan
2 Department of Pathology, Faculty of Pharmaceutical Science, Setsunan University, Hirakata, Osaka 573-0101, Japan
3 Department of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan

Correspondence: Address correspondence to: Shuuichi Matsushima, Pathology Section, Drug Safety Evaluation, Developmental Research Laboratories, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan; e-mail:shuuichi.matsushima{at}shionogi.co.jp

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.

Key Words: Iron lactate • parathyroid gland • PTH • ultrastructure • osteoclast


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