Ninety-day experimental hyperthyroidism in male rats: Effects on muscle contractility, fiber composition, oxidative...

Hyperthyroidism generates a hypermetabolic state that promotes adaptations in the skeletal muscle and peripheral nerves leading to deleterious effects. However, there is a paucity of data and conflicting evidence on the influence of thyroid hormones on muscles with predominantly glycolytic fibers and on peripheral nerves. We assessed the contractility, oxidative stress, and muscle fiber composition in the extensor digitorum longus (EDL) and diaphragm, in addition to assessing the nerve conduction in isolated sciatic nerve in a Wistar rat model of chronic hyperthyroidism, induced by levothyroxine over 13 weeks. In hyperthyroid rats, the EDL increased the speed of relaxation associated with loss of muscle mass and reduction in superoxide dismutase (SOD) activity. The diaphragm gained resistance to fatigue associated with an increment in type IIa fibers at the expense of type I and IIb fibers and an increase in SOD and catalase (CAT) activities. In the sciatic nerve, latency, time to peak, and duration of compound action potential were maintained. Chronic hyperthyroidism elicits differential muscle-specific adaptations. While the diaphragm enhances fatigue resistance and antioxidant response, the EDL undergoes atrophy and diminished antioxidant capacity. The observed changes in the sciatic nerve highlight the systemic impact of hyperthyroidism beyond direct muscle effects.