ROLE OF MITOCHONDRIAL DYSFUNCTION IN STATIN-INDUCED MYOPATHY

Abstract

Statins are highly effective lipid-lowering agents used for cardiovascular disease prevention, but their clinical utility is sometimes limited by the onset of myopathy, a condition ranging from mild muscle pain to severe rhabdomyolysis. Mitochondrial dysfunction has emerged as a key contributor to statin-induced myopathy, though the precise mechanisms remain underexplored.This study aimed to investigate the role of mitochondrial impairment in statin-induced myopathy by evaluating mitochondrial bioenergetics, oxidative stress, apoptotic signaling, and muscle damage markers following statin exposure. C57BL/6 mice and skeletal muscle cells were given atorvastatin, simvastatin and rosuvastatin.  OCR, the process of ATP synthesis, maximum respiration, the membrane potential in mitochondria, reactive oxygen species (ROS), levels of coenzyme Q10 (CoQ10), caspase-3 activity and creatine kinase in the serum were all important factors under study.  The reasons for mitochondrial dysfunction contributing to myopathy were explored using ANOVA and correlation analysis. Treatment with statins led to significant declines in OCR, ATP production and respiration, significantly more by simvastatin than by other statins which may reflect impaired mitochondrial function.  It was found that all types of statins caused a strong decrease in both mitochondrial function and the level of CoQ10, while increasing reactive oxygen species.  The rise in caspase-3 confirmed that the mitochondria were causing apoptosis.  People treated with the medicine all had higher serum CK levels, indicating muscle damage.  By analyzing the data, a correlation was found between levels of ROS and CoQ10, CK and CoQ10 and CK and ATP. This shows that statins cause oxidative stress, kill cells and harm muscles by interfering with mitochondria.  When all parameters were considered, simvastatin had the most obvious benefits.  The findings support prescribing specific statin medication for individuals and suggest that taking CoQ10 and monitoring mitochondrial function may be helpful for patients prone to statin myopathy.