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 language | English |
|---|---|
| Pages (from-to) | 72-80 |
| Number of pages | 9 |
| Journal | Muscle and Nerve |
| Volume | 47 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2013 |
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Keywords
- Atorvastatin
- NCX 6560
- Nitric oxide
- Skeletal muscle
- Statin myopathy
ASJC Scopus subject areas
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Physiology (medical)
- Physiology
Cite this
Nitric oxide prevents atorvastatin-induced skeletal muscle dysfunction and alterations in mice. / D'Antona, Giuseppe; Mascaro, Anna; Monopoli, Angela; Miglietta, Daniela; Ongini, Ennio; Bottinelli, Roberto.
In: Muscle and Nerve, Vol. 47, No. 1, 01.2013, p. 72-80.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nitric oxide prevents atorvastatin-induced skeletal muscle dysfunction and alterations in mice
AU - D'Antona, Giuseppe
AU - Mascaro, Anna
AU - Monopoli, Angela
AU - Miglietta, Daniela
AU - Ongini, Ennio
AU - Bottinelli, Roberto
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - Atorvastatin
KW - NCX 6560
KW - Nitric oxide
KW - Skeletal muscle
KW - Statin myopathy
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UR - http://www.scopus.com/inward/citedby.url?scp=84871268381&partnerID=8YFLogxK
U2 - 10.1002/mus.23465
DO - 10.1002/mus.23465
M3 - Article
VL - 47
SP - 72
EP - 80
JO - Muscle and Nerve
JF - Muscle and Nerve
SN - 0148-639X
IS - 1
ER -