Protective Effect of Edaravone on Doxorubicin-Induced Thyroid Dysfunction in Rats Revealed by 99mTc Pertechnetate Thyroid Gland Scintigraphy and Biochemical Methods.

Background and

Objectives

Doxorubicin is an antineoplastic drug used to treat cancer. However, side effects limit its use. Edaravone (EDO) is a recently discovered, powerful drug with antioxidant properties. The aim of the present study was to show the negative effects of doxorubicin and the protective effect of EDO on the thyroid gland using scintigraphic and biochemical methods. Materials and

Methods

Thirty-five male Wistar rats were randomly divided into five groups (n = 7) to establish the following study groups: control, doxorubicin, and 1, 10, or 30 mg/kg EDO. DOX (18 mg/kg cumulative intraperitoneal injection (i.p.) was performed on the 19th, 20th, and 21st days of the experiment. EDO (1, 10, and 30 mg/kg) was administered on the first day of the trial and continued for 21 days. These groups also received i.p. injections of DOX (18 mg/kg) on the 19th, 20th, and 21st days of the experiment. On the 22nd day of the experiment, scintigraphic imaging of the thyroid glands of rats was performed using 99mTc pertechnetate as the radiopharmaceutical. Serum levels of T3, T4, TSH, NLRP3, IL-1β, and IL-18, as well as thyroid tissue levels of MDA, TNF-α, and IL-6, were determined using the ELISA method.

Results

DOX significantly reduced 99mTc pertechnetate uptake in the thyroid gland compared to the control group (p < 0.001). It reduced plasma levels of thyroid hormones T3 (p < 0.001) and T4 (p < 0.001) while increasing TSH levels (p < 0.01). Additionally, NLRP3, IL-1β, IL-18, MDA, TNF-α, and IL-6 levels were significantly increased in the DOX group compared with the control group (all p < 0.001). Pretreatment with EDO significantly attenuated doxorubicin-induced abnormalities in the thyroid gland (p < 0.001).

Conclusions

The data from scintigraphic and biochemical analyses revealed the development of hypothyroidism after doxorubicin administration in rats. It was shown that pretreatment with EDO could partially prevent hypothyroidism caused by doxorubicin.