Simvastatin induces impairment in skeletal muscle while heart is protected

Sirvent, Pascal; Bordenave, Sylvain; Vermaelen, Marianne; Roels, Belle; Vassort, Guy; Mercier, Jacques; Raynaud, E; Lacampagne, Alain

doi:10.1016/j.bbrc.2005.10.108

Cited by 105 publications

(91 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…14,17,104 Current reports suggest that the SLC16 family of transporters, responsible for lactic acid transport across plasma membrane into muscle, also interacts with statins. 105,106 Inhibition of SLC16A4, which is primarily expressed in skeletal but not cardiac myocytes, paralleling the site of clinical myopathy, is reported to attenuate statin-induced myopathy in vitro. 106,107 This may be a good candidate gene for statin toxicity studies.…”

Section: Genetic Influences On Statinmediated Adverse Drug Reactionsmentioning

confidence: 99%

Clinical implications of pharmacogenomics of statin treatment

Mangravite¹,

Thorn

Krauss³

2006

Pharmacogenomics J

146

132

View full text Add to dashboard Cite

Section: Genetic Influences On Statinmediated Adverse Drug Reactionsmentioning

confidence: 99%

Clinical implications of pharmacogenomics of statin treatment

Mangravite¹,

Thorn

Krauss³

2006

Pharmacogenomics J

146

132

View full text Add to dashboard Cite

“…The histological and physiological changes induced by simvastatin might be of multifactorial etiology. Previous researches [30,31] reported mitochondrial impairment and alteration of Ca2+ homeostasis specifically in skeletal muscle due to preferential uptake of statins by monocarboxylate transporter (MCT4). In addition, statininduced skeletal myopathy might be due to depletion of the isoprenoid pool by statins (HMG-CoA reductase inhibitors) with subsequent generalized insufficient protein modification inducing myopathy [32] .…”

Section: Discussionmentioning

confidence: 99%

The Possible Protective Role of Ginger Extract Versus Vitamin E Against Simvastatin-Induced Skeletal Myotoxicity in Adult Male Albino Rats: Histological, Physiological and Biochemical Study

Hamid¹,

Mola²,

Meligy³

et al. 2017

Egyptian Journal of Histology

View full text Add to dashboard Cite

Introduction: Statins are group of drugs used to reduce total and low density lipoprotein (LDL)-cholesterol level and to reduce the morbidity and mortality of cardiovascular diseases. Meanwhile, induced skeletal muscle-specific mitochondrial impairment, oxidative stress and myotoxicity are serious side effects . Vitamin E and ginger extract are well known potent antioxidants. Aim: To study the possible protective effect of ginger extract versus vitamin E against simvastatin-induced skeletal muscle histological and the associated biophysiological changes. Materials and Methods: Forty adult male albino rats were randomly divided into four equal groups (10 rats, each).; Group 1: was the control rats. Group 2: received 0.54 mg/kg/day simvastatin orally for 8 weeks. Group 3: received concomitant treatment of simvastatin and 30 mg/kg/day vitamin E orally for 8 weeks. Group 4 received concomitant treatment of simvastatin and 500mg/kg/day ginger extract orally for 8 weeks. After sacrifice, specimens were taken from the belly of the quadriceps femoris muscles of all animal groups and processed for light and electron microscopy. Biochemical tests and statistical analysis were done. Results: Group 2 showed focal areas of muscle fiber loss, mononuclear cellular infiltration and variable staining density. Ultra structurally, myofibrillar degeneration and accumulation of numerous giant infrequently damaged mitochondria were observed. The skeletal muscle fibers of animals from group 3 and group 4, both were markedly improved. Group 4 revealed obviously normal mitochondria. Conclusion: Administration of simvastatin for 8 weeks induced histological, physiological and biochemical skeletal myotoxic effects. These effects were greatly ameliorated by concomitant administration vitamin E or ginger extract. Ginger extract was more effective.

show abstract

“…23 Moßhammer et al reported that it is not clear whether MCT4-mediated transport of statins across membranes of myocytes plays a role in myopathy. 24 We found that statin-induced cytotoxicity was associated with intracellular accumulation of statins.…”

Section: Discussionmentioning

confidence: 99%