Dronedarone and Amiodarone Induce Dyslipidemia and Thyroid Dysfunction in Rats

Area of Science:

• Pharmacology
• Endocrinology
• Toxicology

Background:

• Amiodarone, a thyroid hormone analog, is known to cause dyslipidemia and thyroid dysfunction.
• The effects of dronedarone on lipid metabolism and the combined impact of both drugs on thyroid function and lipids remain largely uncharacterized.

Purpose of the Study:

• To investigate the effects of dronedarone and amiodarone on lipid metabolism and thyroid function in a rat model.
• To compare the lipid-altering and thyroid-disrupting effects of amiodarone and dronedarone, with and without polyene phosphatidylcholine co-administration.

Main Methods:

• Male Sprague-Dawley rats were administered amiodarone, dronedarone, or vehicle for 13 weeks.
• Plasma lipid profiles (triglycerides, total cholesterol, LDL-c, HDL-c) and thyroid hormones (FT3, FT4) were measured at multiple time points.
• Thyroid gland histopathology, Bcl-2 protein expression, and mRNA levels of thyroglobulin, deiodinase 1, and thyroid peroxidase were assessed.

Main Results:

• Dronedarone initially increased FT3 and FT4, then decreased them, indicating a biphasic effect (hyperthyroidism then hypothyroidism). Amiodarone consistently lowered FT3, suggesting hypothyroidism.
• Both drugs elevated triglycerides, total cholesterol, and HDL-c; the LDL-c/HDL-c ratio was lowest with amiodarone.
• Dronedarone increased Bcl-2 expression, while both drugs altered thyroid-related gene expression (Tg, D1).

Conclusions:

• Both amiodarone and dronedarone induce dyslipidemia, characterized by increased total cholesterol, LDL-c, and HDL-c.
• The observed lipid alterations are likely associated with drug-induced thyroid dysfunction.