Spleen-Specific Development of Germinal Centers in Rats Treated with Antithyroid Drugs
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概要
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The antithyroid drugs (ATDs) methimazole (MMI) and propylthiouracil (PTU) have been used for treatment of hyperthyroidism for more than several decades, despite the fact that they are associated with adverse drug reactions that are thought to be autoimmune mediated. We therefore examined histopathologic responses in the immune system in male and female rats given MMI (2, 20 and 200 mg/kg/day, p.o., in experiment 1; 200 mg/kg/day, p.o., in experiment 3) or PTU (25 and 250 mg/kg/day, p.o., in experiment 2; 200 mg/kg/day, p.o., in experiment 3) for two weeks. In experiments 1 and 2, highest doses of MMI and PTU induced histopathologic changes in the spleen consistent with those in experiment 3 without any changes in the other peripheral lymphoid organs and tissues. In experiment 3, histopathological evaluation of the spleen along with hematological and bone marrow examinations were performed. In both male and female rats, MMI or PTU induced histopathological changes in the spleen characterized by development of germinal centers and an increase in the number of IgG-positive plasma cells in the red pulp; these changes were most prevalent in the MMI-treated female rats. Total red and white blood cell counts were decreased in the MMI-treated male and female rats; lymphocytes and monocytes were lower in male and female rats, respectively. Bone marrow nucleated cells were significantly lower in the MMI-treated males. This is the first study to demonstrate that ATDs induce spleen specific B-cell reactions in rats.
- 日本毒性病理学会の論文
著者
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Isobe Mitsui
Safety & Pharmacokinetics Research Department Teikoku Hormone Mfg. Co. Ltd.
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SHIBATA Seiji
Safety & Pharmacokinetics Research Dep., Teikoku Hormone Mfg. Co., Ltd.
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Araki Sei-ichi
Safety & Pharmacokinetics Research Department, Teikoku-Hormone Mfg. Co., Ltd.
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Fukui Norio
Safety Research Department Teikoku Hormone Mfg. Co. Ltd.
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Fukui Motoko
Safety Research Department Developmental Research Center Aska Pharmaceutical Co. Ltd.
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Shibata Seiji
Safety Research Department, ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa213-8522, Japan
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Sakai Kuniyoshi
Product Research Department, ASKA Pharmaceutical Co., Ltd., 3-4-3 Sakaecho, Hamura, Tokyo 205-8501, Japan
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Hasegawa Yuko
Product Research Department, ASKA Pharmaceutical Co., Ltd., 3-4-3 Sakaecho, Hamura, Tokyo 205-8501, Japan
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Nagasaki Shuji
Drug Discovery Department, ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa213-8522, Japan
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Hisada Shigeru
Developmental Research Center, ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa213-8522, Japan
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Fukui Norio
Safety Research Department, ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa213-8522, Japan
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