Formoterol induces muscle regeneration through myogenic regulatory factor MyoD in rat model of statin-induced myopathy

Abstract

Background and Objective: Statins can induce myopathy; however, the impact on muscle regeneration remains unclear. β2-agonists may mitigate statin myotoxicity. This study investigated the effects of simvastatin and formoterol on skeletal muscle regeneration and injury using a rat model. Methods: Adult Sprague-Dawley rats (n = 90) were divided into three groups: control (A), simvastatin treatment (B), and simvastatin plus formoterol treatment (C). The rats were kept at room temperature for 3 months where an animal house diet was available ad libitum. Simvastatin was administered orally once a day, by oral gavage for 12 weeks; formoterol was concurrently administered to one group. Extensor digitorum longus muscles were analyzed for the myogenic differentiation factor (MyoD) by immunohistochemistry. Serum lactate dehydrogenase (LDH) levels were quantified as a marker of muscle damage. Results: MyoD-positive myonuclei were significantly increased in the C group (simvastatin plus formoterol group) compared to the A and B Groups (control and simvastatin-only groups) (p < 0.05). Serum LDH levels were significantly lower in group C than in groups A and B (p < 0.05). Conclusion: Formoterol alleviates statin-associated muscle injury in a rat model as evidenced by increased MyoD expression and decreased LDH levels. The activation of dormant satellite cells and increased expression of MyoD indicate the potential of formoterol to promote muscle regeneration.