Nitric oxide prevents atorvastatin-induced skeletal muscle dysfunction and alterations in mice

Giuseppe D'Antona, Anna Mascaro, Angela Monopoli, Daniela Miglietta, Ennio Ongini, Roberto Bottinelli

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)72-80
Number of pages9
JournalMuscle and Nerve
Volume47
Issue number1
DOIs
Publication statusPublished - Jan 2013

Keywords

  • Atorvastatin
  • NCX 6560
  • Nitric oxide
  • Skeletal muscle
  • Statin myopathy

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)
  • Physiology

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