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Nitric oxide prevents atorvastatin‐induced skeletal muscle dysfunction and alterations in mice
Author(s) -
D'Antona Giuseppe,
Mascaro Anna,
Monopoli Angela,
Miglietta Daniela,
Ongini Ennio,
Bottinelli Roberto
Publication year - 2013
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.23465
Subject(s) - atorvastatin , skeletal muscle , medicine , endocrinology , myopathy , creatine kinase , nitric oxide , chemistry , creatine
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 atorvastatin. Methods: C57BL/6 mice received atorvastatin 40 mg/kg/day or an equivalent dose of NCX 6560 for 2 months. Muscle function assessed by treadmill test, serum creatine kinase (CK) activity, citrate synthase (CS) activity, and muscle histology 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, 2013