Spleen-Specific Development of Germinal Centers in Rats Treated with Antithyroid Drugs

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

The Precautionary Role of Nigella Sativa Oil in Methimazole Associated Toxicity on the Structure of Spleen in Adult Male Albino Rats: Histological, Hematological and Morphometric Study

“…In the present work, rats treated with MMZ recorded significant decrease in the final body weights which is consistent with [20], who added that this decrease is due to failure of this group to gain body weights throughout the experiment. Such weight gain reduction in MMZ-group could be explained by the fact that thyroid hormones are essential for growth stimulation and their diminished levels may be associated with retarded weight gain in addition to diminished food intake [26] .…”

“…These results are parallel with those of Fukui et al, [20] who stated that MMZ affects hematopoiesis process with subsequent reduction in blood cells formation and lower total leukocytes and lymphocytes compared to the normal one.…”

“…Group IV (MMZ-treated group): rats were treated with methimazole (MMZ) in dose of 20 mg/kg/day dissolved in distilled water for 4 weeks [20] .…”

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“…The increase in thyroid weight may be due to reactive hyperplasia, which is consistent with the enlarged volume of the thyroid at the 2nd week compared with that in the control group (Supplementary Figure S6B) (Shibutani et al, 2009). The decrease in liver and spleen weight may be due to ATDsinduced injury, which is consistent with the results for the following biochemical indicators (Cano-Europa et al, 2011;Fukui et al, 2013).…”

Protective effects of GM-CSF in experimental neonatal hypothyroidism

“…Furthermore, hypothyroidism correlated with immune dysfunction and decreased count of immune cells in spleen and bone marrow [38]. MMI, as one of the anti-thyroid drugs, could reduce the myeloid colony growth leading to agranulocytosis [39,40].…”