Hashim Omar Ammar, Numan Intesar Tarik, Mohammed Nadia Hameed
Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Iraq.
Department of Pharmacy, Alnukhba University College, Iraq.
Toxicol Rep. 2025 Jan 31;14:101942. doi: 10.1016/j.toxrep.2025.101942. eCollection 2025 Jun.
The use of Simvastatin has been reported to induced muscle myopathy, with no effective preventive measures. The study objective is to study the protective effect of CoQ10, vitamin E, and their combination to prevent simvastatin-induced skeletal muscle myopathy in rat models and explore possible mechanisms by measuring muscle biomarkers and histopathological changes. All rats (n = 49) received 80 mg/kg/day of simvastatin to induce myopathy for 30 days, the study includes 7 groups (n = 7): negative control, CMC and cotton seed oils vehicles, simvastatin induction, CoQ10, vitamin E and combination of vitamin E and CoQ10 groups; rats in the intervention groups received either 100 mg/kg CoQ10 or 40 mg/kg vitamin E or their combination once daily orally for 30 days. At the end of the experiment, rats were euthanized by cervical dislocation, and blood and the collected tissue samples were collected to measure creatinine kinase (CKM), malondialdehyde (MDA), total antioxidant capacity (TAOC), inducible nitric oxide synthase-2 (iNOS2), and aldolase. In addition, gastrocnemius muscle histopathology was examined. Treatment with CoQ10, vitamin E, or their combination significantly reduced the levels of CKM, aldolase, iNO2, and MDA and increased TAOC compared to the simvastatin induction group. The combination group showed a superior protective effect than either drug alone. Treatment with vitamin E and CoQ10 showed mild vacuolation and cytoplasm with focal splitting and fragmentation of muscle fibers, scattered central nuclei, and eosinophilic cytoplasm. In conclusion, CoQ10 and vitamin E combined showed a superior protective effect against simvastatin-induced myopathy through antioxidant and antiapoptotic pathways.
据报道，使用辛伐他汀会诱发肌肉肌病，且没有有效的预防措施。本研究的目的是研究辅酶Q10、维生素E及其组合对预防大鼠模型中辛伐他汀诱发的骨骼肌肌病的保护作用，并通过测量肌肉生物标志物和组织病理学变化来探索可能的机制。所有大鼠（n = 49）接受80 mg/kg/天的辛伐他汀以诱发肌病30天，该研究包括7组（n = 7）：阴性对照组、羧甲基纤维素和棉籽油载体组、辛伐他汀诱导组、辅酶Q10组、维生素E组以及维生素E和辅酶Q10联合组；干预组的大鼠每天口服一次100 mg/kg辅酶Q10或40 mg/kg维生素E或它们的组合，持续30天。在实验结束时，通过颈椎脱臼法对大鼠实施安乐死，并采集血液和组织样本以测量肌酸激酶（CKM）、丙二醛（MDA）、总抗氧化能力（TAOC）、诱导型一氧化氮合酶-2（iNOS2）和醛缩酶。此外，还检查了腓肠肌的组织病理学。与辛伐他汀诱导组相比，辅酶Q10、维生素E或它们的组合治疗显著降低了CKM、醛缩酶、iNO2和MDA的水平，并提高了TAOC。联合组显示出比单独使用任何一种药物更好的保护作用。维生素E和辅酶Q10治疗显示出轻度空泡化以及肌纤维局部分裂和断裂的细胞质、散在的中央核和嗜酸性细胞质。总之，辅酶Q10和维生素E联合使用通过抗氧化和抗凋亡途径对辛伐他汀诱发的肌病显示出更好的保护作用。
