title: Nitric oxide prevents atorvastatin-induced skeletal muscle dysfunction and alterations in mice.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Molecular Medicine, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Antona
authors.forename: Anna
authors.initials: A
authors.lastname: Mascaro
authors.forename: Angela
authors.initials: A
authors.lastname: Monopoli
authors.forename: Daniela
authors.initials: D
authors.lastname: Miglietta
authors.forename: Ennio
authors.initials: E
authors.lastname: Ongini
authors.forename: Roberto
authors.initials: R
authors.lastname: Bottinelli
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D001284:Atrophy; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C524539:NCX 6560; D020030:Nitric Oxide Donors; D011758:Pyrroles; D009569:Nitric Oxide; D000069059:Atorvastatin; D007770:L-Lactate Dehydrogenase; D002950:Citrate (si)-Synthase; D003402:Creatine Kinase; D018995:Myosin Heavy Chains