Nitric oxide prevents atorvastatin-induced skeletal muscle dysfunction and alterations in mice
Giuseppe D'Antona MD PhD1,2, Anna Mascaro BSc3, Angela Monopoli PhD4, Daniela Miglietta PharmD4, Ennio Ongini PhD4,†,*, , Roberto Bottinelli MD PhD3
DOI: 10.1002/mus.23465
Copyright © 2012 Wiley Periodicals, Inc.
Issue
Muscle & Nerve
Accepted Article (Accepted, unedited articles published online for future issues)
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Keywords:
statin myopathy;skeletal muscle;atorvastatin;NCX 6560;nitric oxide
Abstract
Introduction:
Myopathy is the most common side effect of statins. Since 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 to atorvastatin.
Methods:
C57BL/6 mice received atorvastatin 40 mg/kg/day or an equivalent dose of NCX 6560 for 2 months. Muscle function was assessed treadmill test, serum creatine kinase (CK) activity, citrate synthase (CS) activity, and muscle histology.
Results:
Atorvastatin significantly (P<0.001) reduced muscle endurance, increased serum CK 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.
Conclusion:
These findings suggest that NO may prevent statin-induced myopathy.
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Articolo pagato oppure c'è qualcosa di vero ???
In ogni caso per le statine, essendo che le generiche funzionano abbastanza bene, è tutto da valutare il rapporto costi/benefici per le Pharma che intendano portare avanti la sperimentazione della molecola.