Tetracycline as a Peroxidase Inhibitor: Possible Implications for Thyroid Hormone Biosynthesis

Tetracycline (TC), a widely used broad-spectrum antibiotic, was experimentally and theoretically investigated for its potential effect on thyroid hormone biosynthesis through interaction with thyroid peroxidase (TPO). Horseradish peroxidase (HRP) was used as a model of TPO, while FeTPPCl was employed as a model of the active site of the enzyme. The inhibitory effect of TC on the catalytic oxidation of iodide to active iodine was studied spectrophotometrically through the formation of triiodide (I₃^-), and the IC₅₀ value was determined. Kinetic studies using Michaelis-Menten and Lineweaver-Burk analysis demonstrated that TC acts as a reversible non-competitive inhibitor of HRP, leading to decreased Km and Vmax values and the formation of the ESI complex. Molecular docking calculations further supported the experimental findings, indicating that TC binds at a site different from the active center of the enzyme. The results suggest that tetracycline may interfere with thyroid hormone biosynthesis by inhibiting TPO-mediated iodide oxidation, revealing a possible mechanism associated with thyroid-related side effects during prolonged antibiotic administration.