1. Nitric oxide prevents atorvastatin-induced skeletal muscle dysfunction and alterations in mice
- Author
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Daniela Miglietta, Roberto Bottinelli, Ennio Ongini, Angela Monopoli, Anna Mascaro, and Giuseppe D'Antona
- Subjects
medicine.medical_specialty ,biology ,Side effect ,Physiology ,Chemistry ,Atorvastatin ,Skeletal muscle ,medicine.disease ,Diaphragm (structural system) ,Nitric oxide ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Atrophy ,medicine.anatomical_structure ,Endocrinology ,Physiology (medical) ,Internal medicine ,medicine ,biology.protein ,Citrate synthase ,Neurology (clinical) ,medicine.symptom ,Myopathy ,medicine.drug - Abstract
Introduction: Myopathy is the most common side effect of statins. Because nitric oxide (NO) has a key role in regulating skeletal muscle function, we studied whether the NO-donating atorvastatin NCX 6560 could show a better profile on skeletal muscle function and structure compared with ator- vastatin. Methods: C57BL/6 mice received atorvastatin 40 mg/ kg/day or an equivalent dose of NCX 6560 for 2 months. Mus- cle function assessed by treadmill test, serum creatine kinase (CK) activity, citrate synthase (CS) activity, and muscle histol- ogy were evaluated. Results: Atorvastatin significantly (P < 0.001) reduced muscle endurance, increased serum CK by 6- fold, and induced muscle fiber atrophy. Conversely, NCX 6560 preserved muscle function, prevented CK increase and did not modify muscle structure. Interestingly, atorvastatin reduced CS activity, a marker for mitochondrial function, in gastrocnemius, diaphragm, and heart, whereas NCX 6560 prevented such decrease. Conclusions: These findings suggest that NO may prevent statin-induced myopathy. Muscle Nerve 47: 72-80, 2013
- Published
- 2012
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