Protective Role of Selenium Against Thyroid Toxicity Induced by Lithium Carbonate in Albino Rats: Biochemical and Immunohistochemical Study

Background: Although lithium (LC) is considered the successful drug used for the treatment of psychiatric disorders, it has many toxic effects on human organs, particularly the thyroid gland. Thyroid health has been associated with the content of selenium as a component of strong antioxidant, whereas thyroid dysfunctions such as goiter are associated with low selenium status. Aim of the work: The aim of the current study was to clarify the modulation role of Se over structural and functional affection of the thyroid gland after 30 days’ use of LC. Accordingly, the effects of LC administration on the thyroid gland and to evaluation of selenium's role as a well-known antioxidant in the protection of the gland against these hazardous effects were investigated. The effect of lithium carbonate, selenium and co-treatment with these two drugs on Klotho protein immunohistochemical expression in the thyroid gland was also, evaluated. Methods: Twenty-four adult male albino rats aged 3 months weighing 200-250 gm were used. The rats were equally divided into four groups (6 rats each): Group I as a control, Group II as selenium-treated rats (a dose of Se, 1 mg/kg with water), Group III as lithium carbonate (LC) treated rats (25 mg/kg of LC injected intraperitoneally, twice a day), and Group IV as LC +Se treated rats (Received the same dose of both LC + Se respectively). The rats were treated with LC and Se doses for 30 days. At the end of the experiment, the rats were weighed, and both blood and thyroid tissue samples were taken for hormonal, oxidative stress, histological, and immunohistochemical investigations using hematoxylin and eosin stain, PAS stain, and α-Klotho immunohistochemistry. Results: In LC-treated rats, a highly significant increase of MDA as a lipid peroxide marker of cellular oxidative stress and serum TSH while, a decrease of FT4 was recorded compared to control rats. Also, degenerative changes in the thyroid gland in the form of decreased or absent colloid and fusion of the disrupted follicles with mild or absent positive α-Klotho immunoreactivity. LC+selenium treated group revealed a nearly normal appearance of thyroid gland architecture, improved thyroid function, and strong expression of α-Klotho immunoreactivity compared to non-treated LC-intoxicated rats. In addition, MDA as a lipid peroxide marker of cellular oxidative stress significantly reduced in the serum compared to LC-group, indicating the antioxidant activity of Se to protect the thyroid against the toxicity of LC. Moreover, control rats who received Se only as a protective agent showed preserved non-change in the thyroid texture and normal function without initiated MDA oxidative stress. Conclusion: LC had harmful effects on thyroid structure and function. Concomitant administration of selenium preserved to a great extent the thyroid gland architecture and function. The protective role of Se proceeds through suppression of cellular oxidative stress and promoting antioxidant activity of the thyroid gland which was evidenced by expression of Klotho immunostain.