Abstract
Statins, anti-hyperlipidemic drugs, are associated with skeletal muscle myopathy. New strategies to preserve muscle strength in statin-induced myopathy (SIM) are needed. This study assessed the effect of quercetin on simvastatin-induced myopathy in adult male rats, focusing on the modulation of autophagy-apoptosis crosstalk. Forty adult albino male rats were randomly divided into four groups. The control group (C) received distilled water, the quercetin group (Q) received quercetin (50 mg/kg/day, orally), the simvastatin (S) group received simvastatin (80 mg/kg/day, orally), and the quercetin + simvastatin (Q + S) group received both quercetin (50 mg/kg/day) and simvastatin (80 mg/kg/day, orally), all for 30 days. Gastrocnemius muscle contractility, muscle weight/tibial length ratio, histopathological examination, serum creatine kinase (CK) levels, oxidative stress markers, lipid profile, autophagy-related gene expression (LC3 and LAMP2), and apoptosis markers (BAX and caspase-3) were evaluated. Simvastatin induced muscle atrophy and significantly elevated serum CK levels. These changes were associated with increased oxidative stress, altered expression of autophagy-related genes (increased LC3 and decreased LAMP2), and increased expression of the apoptotic markers BAX and Caspase-3. Quercetin ameliorated these alterations by improving muscle contractility, reducing CK levels and oxidative stress, attenuating apoptosis, and modulating autophagy-related gene expression. Quercetin alleviated simvastatin-induced myopathy through its antioxidant and antiapoptotic effects and was associated with modulation of autophagy-related gene expression. These findings suggest that quercetin may represent a promising adjuvant strategy for mitigating statin-associated myopathy. Further studies evaluating autophagic flux at the protein level are warranted to clarify the underlying mechanisms.