An increase of oxidative stress markers and the alteration of the antioxidant enzymatic system are associated with spleen damage caused by methimazole-induced hypothyroidism

Abstract

Methimazole is the most widely used antithyroid drug in Europe and North America, but it causes several undesirable side effects, such as hematological dysfunctions and immunosuppression. Our aim in this work was to compare, over a time course, markers of oxidative stress, the redox environment, the antioxidant enzymatic system, and the glutathione cycle in the spleen of rats with methimazole- or thyroidectomy-caused hypothyroidism. We used 70-male Wistar rats divided into four groups: 1) euthyroid; 2) sham thyroidectomy; 3) thyroidectomy-caused hypothyroidism, with parathyroid reimplant; and 4) methimazole-caused hypothyroidism. Five rats of the euthyroid- and methimazole-caused hypothyroidism groups were killed at the end of weeks 1, 2, 3, and 4 after treatment, and 5 rats of the sham thyroidectomy and thyroidectomy-caused hypothyroidism groups were killed at the end of weeks 2, 4, and 8 after the surgical procedure. Each spleen was excised and stored at −70°C until oxidative stress, REDOX environment, and the antioxidant enzymatic-system markers were tested. The histological study showed that only methimazole-induced hypothyroidism caused cell damage. This damage was associated with an increase of oxidative-stress markers that were not compensated for by the antioxidant system. The increase of the glutathione-cycle enzymes was insufficient to prevent oxidative-stress markers. Methimazole causes oxidative stress and cell damage in the spleen, whereas hypothyroidism per se does not cause cell damage in this organ. Therefore, it is necessary to develop new antithyroid drugs without causing oxidative stress and cellular damage.

Keywords::

• Methimazole
• hypothyroidism
• thyroidectomy
• spleen damage
• oxidative stress

Acknowledgments

This study was partially supported by SIP-IPN 20080113 and 20090485. RO-B is a fellow of EDI, COFAA, and SNI; VB-V and MP-R are fellows of CONACyT and PIFI-COFFA. The authors thank Ellis Glazier Ph.D. for editing the English-language text.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.