title: Ultrastructural and morphometrical evaluation of the parathyroid gland in iron-lactate-overloaded rats.
abstract: 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.
authors.affiliation: Pathology Section, Drug Safety Evaluation, Developmental Research Laboratories, Shionogi & Co., Ltd, Toyonaka, Osaka 561-0825, Japan. shuuichi.matsushima@shionogi.co.jp
authors.forename: Shuuichi
authors.initials: S
authors.lastname: Matsushima
authors.forename: Noriko
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Kae
authors.initials: K
authors.lastname: Fujisawa-Imura
authors.forename: Kae
authors.initials: K
authors.lastname: Fujisawa-Imura
authors.forename: Maruko
authors.initials: M
authors.lastname: Hoshimoto
authors.forename: Nobuo
authors.initials: N
authors.lastname: Takasu
authors.forename: Mikinori
authors.initials: M
authors.lastname: Torii
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Ozaki
authors.forename: Isao
authors.initials: I
authors.lastname: Narana
authors.forename: Takao
authors.initials: T
authors.lastname: Kotani
mesh_terms: D000818:Animals; D005296:Ferrous Compounds / Q000633:toxicity*; D019190:Iron Overload / Q000378:metabolism*; D007773:Lactates / Q000633:toxicity*; D008297:Male; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010280:Parathyroid Glands / Q000473:pathology / Q000648:ultrastructure*; D044162:Parathyroid Hormone-Related Protein / Q000097:blood / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D005296:Ferrous Compounds; D007773:Lactates; D044162:Parathyroid Hormone-Related Protein