Melatonin ameliorates ketoconazole-induced increase in thyroid function

Abstract

Background

The antithyroid effect of ketoconazole has been reported. The secretion and action of melatonin in the thyroid gland are also known. However, the possible effect of melatonin on ketoconazole-induced antithyroid effect is unknown.

Objective

We sought to investigate the modulatory effect of ketoconazole and/or melatonin on thyroid function in female rats.

Methods

Groups 1-4 of female rats respectively underwent 14-day treatment with normal saline, 25 mg/kg ketoconazole, 4 mg/kg melatonin and 10 mg/kg melatonin. Groups 5 and 6 both received 14-day treatment with ketoconazole and were respectively treated with 4 mg/kg melatonin and 10 mg/kg melatonin simultaneously. Groups 7 and 8 respectively underwent 14-day pretreatment with 4 mg/kg melatonin and 10 mg/kg melatonin, followed by 14-day administration of ketoconazole to both groups. Groups 9 and 10 were both treated with ketoconazole for 14 days, followed by respective 14-day administration of 4 mg/kg melatonin and 10 mg/kg melatonin.

Results

TSH, T3, T4, and iodine concentrations were increased by separate administration of ketoconazole and either dose of melatonin when compared to control. However, pre-treatment or post-treatment of ketoconazole-treated rats with melatonin abolished the ketoconazole-induced increase in TSH, T3, T4, and iodine while co-administration of ketoconazole with melatonin caused no improvement in the ketoconazole-induced increase in TSH, T3, and T4 except iodine concentration.

Conclusion

Ketoconazole increased thyroid function, which was ameliorated by pre- or post-treatment with melatonin, possibly via modulation of the iodination process.

Keywords: Iodine; Ketoconazole; Melatonin; Thyroid function; Toxicity