Effects of Lithium and Verapamil on Thyroid and Kidney Function in Mice: A Preclinical Study

Lithium (Li) salts are still one of the basic therapies for manic-depressive illness, which has a double-edged nature where the good efficacy is threatened by possible toxicity if Li levels are elevated. The effects of verapamil and N-acetylcysteine (NAC) on Li levels and Li-related toxicity in the thyroid gland and kidneys were studied. Five groups of mice (normal control, Li, verapamil, Li + verapamil, and Li + NAC) were evaluated for levels of urea, creatinine, thyroid hormones (T3 and T4), thyroid-stimulating hormone (TSH), sodium, and potassium after 6 weeks. Li levels were measured in all groups that received Li. Renal and thyroid tissues were assessed histologically. T4 and T3 were significantly elevated in the Li, Li + verapamil, and Li + NAC groups compared to the normal control (p < 0.0001), while TSH was significantly decreased (p < 0.001). Levels of Li, potassium, and urea were elevated by the co-administration of verapamil or NAC, while serum creatinine was significantly decreased compared to the Li-treated group. Verapamil and NAC elevated the serum levels of Li and augmented the effects of Li on the thyroid gland, urea, and potassium levels.