Limits...
Spleen-specific development of germinal centers in rats treated with antithyroid drugs.

Fukui M, Fukui N, Sakai K, Hasegawa Y, Nagasaki S, Shibata S, Araki S, Isobe M, Hisada S - J Toxicol Pathol (2013)

Bottom Line: 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.Bone marrow nucleated cells were significantly lower in the MMI-treated males.

View Article: PubMed Central - PubMed

Affiliation: Safety Research Department, ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa213-8522, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

The number of germinal centers in the spleen of male and female rats treated with antithyroid drugs for 14 days. Results are expressed as means ± SD. PTU, propylthiouracil; MMI, methimazole. *P<0.05; **P<0.01; significantly different from the control group (Aspin-Welch test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3921920&req=5

fig_003: The number of germinal centers in the spleen of male and female rats treated with antithyroid drugs for 14 days. Results are expressed as means ± SD. PTU, propylthiouracil; MMI, methimazole. *P<0.05; **P<0.01; significantly different from the control group (Aspin-Welch test).

Mentions: Micrographs of spleens from rats treated with antithyroid drugs (ATDs) for 14 days. a, control male; b, control female; c, propylthiouracil (PTU)-treated male; d, PTU-treated male; e, methimazole (MMI)-treated male; and f, MMI-treated female. Development of germinal centers is noted in ATD-treated rats (c, d, e and f). HE stain. Bar: 500 µm.


Spleen-specific development of germinal centers in rats treated with antithyroid drugs.

Fukui M, Fukui N, Sakai K, Hasegawa Y, Nagasaki S, Shibata S, Araki S, Isobe M, Hisada S - J Toxicol Pathol (2013)

The number of germinal centers in the spleen of male and female rats treated with antithyroid drugs for 14 days. Results are expressed as means ± SD. PTU, propylthiouracil; MMI, methimazole. *P<0.05; **P<0.01; significantly different from the control group (Aspin-Welch test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921920&req=5

fig_003: The number of germinal centers in the spleen of male and female rats treated with antithyroid drugs for 14 days. Results are expressed as means ± SD. PTU, propylthiouracil; MMI, methimazole. *P<0.05; **P<0.01; significantly different from the control group (Aspin-Welch test).
Mentions: Micrographs of spleens from rats treated with antithyroid drugs (ATDs) for 14 days. a, control male; b, control female; c, propylthiouracil (PTU)-treated male; d, PTU-treated male; e, methimazole (MMI)-treated male; and f, MMI-treated female. Development of germinal centers is noted in ATD-treated rats (c, d, e and f). HE stain. Bar: 500 µm.

Bottom Line: 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.Bone marrow nucleated cells were significantly lower in the MMI-treated males.

View Article: PubMed Central - PubMed

Affiliation: Safety Research Department, ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa213-8522, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus