Fluvastatin-induced alterations of skeletal muscle function in hypercholesterolaemic rats

Márta Füzi, Zoltán Palicz, János Vincze, Julianna Cseri, Zita Szombathy, I. Kovács, Anna Oláh, P. Szentesi, Pál Kertai, G. Paragh, L. Csernoch

Research output: Article

9 Citations (Scopus)

Abstract

Although statins, the most widely used drugs in the treatment of hyperlipidaemia, are generally accepted as efficient and safe drugs their side-effects on skeletal muscle have been reported with increasing frequency. The lack of an animal model in which these side effects would consistently be observed is one of the important drawbacks in studying statin associated myopathy. To overcome this and enable the studying of the effects of fluvastatin on skeletal muscles an animal model with high blood cholesterol levels was developed. In these animals cholesterol levels rose more than seven fold (from 1.5 ± 0.1 to 10.7 ± 2.0 mmol/l; n = 15 and 16) with a dramatic increase in low density lipoprotein/high density lipoprotein ratio (from 0.29 ± 0.02 to 1.56 ± 0.17). While the latter was reversed by statin treatment, an elevation in blood creatine kinase (CK) level indicated the presence of muscle wasting. Fibers from m. extensor digitorum longus (EDL) showed significant reduction in cross sectional area in the statin treated groups. Statin treatment also decreased the proliferation and fusion of skeletal myotubes in culture. In line with this, resting intracellular calcium concentration ([Ca2+]i) was reduced in statin treated satellite cells and myotubes. On the other hand, in adult skeletal muscle fibers statin treatment increased resting [Ca2+]i (116 ± 4 nM vs. 151 ± 5 nM; n = 33 and 34) and decreased both twitch and tetanic force both in EDL and m. soleus. In addition, in m. soleus the duration of twitch and tetanic force was shortened. These results clearly indicate that statin administration in these animals results in a myopathy characterized by decreased muscle force and elevated plasma CK level.

Original languageEnglish
Pages (from-to)391-401
Number of pages11
JournalJournal of Muscle Research and Cell Motility
Volume32
Issue number6
DOIs
Publication statusPublished - márc. 2012

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fluvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Muscle
Rats
Skeletal Muscle
Skeletal Muscle Fibers
Animals
Muscular Diseases
Creatine Kinase
Blood
Animal Models
Cholesterol
Muscles
Fibers
HDL Lipoproteins
Hypercholesterolemia
Hyperlipidemias
Drug-Related Side Effects and Adverse Reactions
LDL Lipoproteins
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Physiology
  • Cell Biology
  • Biochemistry

Cite this

Fluvastatin-induced alterations of skeletal muscle function in hypercholesterolaemic rats. / Füzi, Márta; Palicz, Zoltán; Vincze, János; Cseri, Julianna; Szombathy, Zita; Kovács, I.; Oláh, Anna; Szentesi, P.; Kertai, Pál; Paragh, G.; Csernoch, L.

In: Journal of Muscle Research and Cell Motility, Vol. 32, No. 6, 03.2012, p. 391-401.

Research output: Article

Füzi, Márta ; Palicz, Zoltán ; Vincze, János ; Cseri, Julianna ; Szombathy, Zita ; Kovács, I. ; Oláh, Anna ; Szentesi, P. ; Kertai, Pál ; Paragh, G. ; Csernoch, L. / Fluvastatin-induced alterations of skeletal muscle function in hypercholesterolaemic rats. In: Journal of Muscle Research and Cell Motility. 2012 ; Vol. 32, No. 6. pp. 391-401.
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abstract = "Although statins, the most widely used drugs in the treatment of hyperlipidaemia, are generally accepted as efficient and safe drugs their side-effects on skeletal muscle have been reported with increasing frequency. The lack of an animal model in which these side effects would consistently be observed is one of the important drawbacks in studying statin associated myopathy. To overcome this and enable the studying of the effects of fluvastatin on skeletal muscles an animal model with high blood cholesterol levels was developed. In these animals cholesterol levels rose more than seven fold (from 1.5 ± 0.1 to 10.7 ± 2.0 mmol/l; n = 15 and 16) with a dramatic increase in low density lipoprotein/high density lipoprotein ratio (from 0.29 ± 0.02 to 1.56 ± 0.17). While the latter was reversed by statin treatment, an elevation in blood creatine kinase (CK) level indicated the presence of muscle wasting. Fibers from m. extensor digitorum longus (EDL) showed significant reduction in cross sectional area in the statin treated groups. Statin treatment also decreased the proliferation and fusion of skeletal myotubes in culture. In line with this, resting intracellular calcium concentration ([Ca2+]i) was reduced in statin treated satellite cells and myotubes. On the other hand, in adult skeletal muscle fibers statin treatment increased resting [Ca2+]i (116 ± 4 nM vs. 151 ± 5 nM; n = 33 and 34) and decreased both twitch and tetanic force both in EDL and m. soleus. In addition, in m. soleus the duration of twitch and tetanic force was shortened. These results clearly indicate that statin administration in these animals results in a myopathy characterized by decreased muscle force and elevated plasma CK level.",
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AU - Szombathy, Zita

AU - Kovács, I.

AU - Oláh, Anna

AU - Szentesi, P.

AU - Kertai, Pál

AU - Paragh, G.

AU - Csernoch, L.

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