Dantrolene and coenzyme Q10 as a suggested combination therapy to statin-induced myopathy in high fat diet rats: A possible interference with ROS/ TGF-β / Smad4 signaling pathway

• Published in: Toxicology and applied pharmacology 2024-04, Vol.485, p.116900-116900, Article 116900
• Main Authors: Zakaria, Sherin, Elshazly, Ahmed M., Alaa, Reem, Elsebaey, Samer
• Format: Article
• Language: English
• Subjects: Ca2; Coenzyme Q10; Dantrolene; Myopathy; Statins
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2024.116900

One of the major hitches for statins' utilization is the development of myotoxicity. Versatile studies reported that the underlining molecular mechanisms including coenzyme Q10 (CoQ10)/ubiquinone depletion, as well as the disturbance in the cytoplasmic Ca2+ homeostasis. Therefore, we investigated the consequences of supplementing CoQ10 and dantrolene, a cytoplasmic Ca2+ reducing agent, in combination with simvastatin. This adjuvant therapy normalized the simvastatin-mediated elevation in serum ALT, AST, CK-MM, as well as tissue Ca2+ content, in addition to suppressing the simvastatin-mediated oxidative stress in simvastatin-treated rats, while having no effect upon statin-induced antihyperlipidemic effect. Additionally, the combination inhibited the simvastatin-induced TGF-β/ Smad4 pathway activation. Collectively, the current study emphasizes on the potential utilization of dantrolene and CoQ10 as an adjuvant therapy to statins treatment for improving their side effect profile. •Ca2+ deregulation and coQ10 depletion contributed to statin-induced myotoxicity.•Dantrolene combined with coenzyme Q10 normalized statins-mediated oxidative stress.•This combination normalized statins-mediated elevation in calcium content.•This combination did not affect the statin-mediated pharmacological activity.