Thyroid and Extrathyroid Effects of Methimazole in Modeling Hypothyroidism with Different Doses of Antithyroid Drug: Morfofunctional Study

Abstract

Aims: Methimazole (MMI) is widely used in experimental thyroidology. However, the effect on thyroid function can vary widely depending on the route of administration and doses of the antithyroid drug. In some cases, it is difficult to determine whether the results obtained are a manifestation of thyroid dysfunction or a direct toxic effect of xenobiotic. The aim of the study was to establish the optimal dose of methimazole for the induction of hypothyroidism with minimal toxic effects on tissues. Study Design: The effect of various doses of methimazole administered intragastrically to rats on thyroid status, histological structure of thyroid, liver and kidney was studied. Place and Duration of Study:  Bashkir institute of Technology and Management (branch) of Moscow State University of Technology and Management n.a. K. G. Razumovsky, city of Meleuz, Bashkir State Medical University, Ufa, Russia, 2018-2019. Methodology: Experiments were conducted on 60 nonlinear white male rats intragastrically administered different doses of methimazole. To assess the thyroid status, the concentration of circulating thyroid hormones in blood plasma and body temperature rhythms were determined. Along with the indicators of thyroid status, morphological changes in the thyroid gland, liver and kidneys were compared in rats that were administered different doses of MMI. Results: Hormonal profile of rats received MMI in the dose 2,5 mg/100 g of body weight. for 3 weeks revealed decrease in mean free T4  (10,8±2,14 against 16,2±0,57 in control, P<0,001), total T3 (3,12±0,57 against 2,36±0,19, P<0,001 with the increase of TSH (0, 12±0,01 against 1,96±0,18, P<0,001). The hypothyroid state in this group of animals is also confirmed by decrease in the arithmetic mean values of body temperature. Conclusion: The results obtained indicate that a dose of 2.5 mg/100 g of b. w. for 3 w. leads to the development of symptoms characteristic of endemic thyroid dysfunction, and is accompanied by minimal toxic effects on tissues.