Toxicity of statins on rat skeletal muscle mitochondria
Open accessAbstract
We investigated mitochondrial toxicity of four lipophilic stains (cerivastatin, fluvastatin, atorvastatin, simvastatin) and one hydrophilic statin (pravastatin). In L6 cells (rat skeletal muscle cell line), the four lipophilic statins (100 micromol/l) induced death in 27-49% of the cells. Pravastatin was not toxic up to 1 mmol/l. Cerivastatin, fluvastatin and atorvastatin (100 micromol/l) decreased the mitochondrial membrane potential by 49-65%, whereas simvastatin and pravastatin were less toxic. In isolated rat skeletal muscle mitochondria, all statins, except pravastatin, decreased glutamate-driven state 3 respiration and respiratory control ratio. Beta-oxidation was decreased by 88-96% in the presence of 100 micromol/l of the lipophilic statins, but only at higher concentrations by pravastatin. Mitochondrial swelling, cytochrome c release and DNA fragmentation was induced in L6 cells by the four lipophilic statins, but not by pravastatin. Lipophilic statins impair the function of skeletal muscle mitochondria, whereas the hydrophilic pravastatin is significantly less toxic.
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Acute statin effects have been studied in isolated mitochondria from L6 cells and skinned human and rat muscle, where simvastatin showed a toxic effect and depressed complex I respiration.
“The acute effect of statins has, however, been studied in isolated mitochondria from L6 cells (a rat skeletal muscle cell line) (39) and in skinned human and rat muscle (16) in which a toxic effect of simvastatin and depressed complex I respiration was found.”
From Simvastatin Effects on Skeletal Muscle (2013) · cites this paper as [39]
Statins decrease mitochondrial membrane potential in a dose-dependent manner.
“Third, it has previously been reported that statins, in a dose-dependent manner, decrease the mitochondrial membrane potential (16,39).”
From Simvastatin Effects on Skeletal Muscle (2013) · cites this paper as [39]
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References 46 · Cited by 263
- Authors
- Kaufmann, P., Török, M., Zahno, A., Waldhauser, K. M., Brecht, K., & Krähenbühl, S.
- Affiliations
- University Hospital of Basel (CH)
- Corresponding author
- Krähenbühl, S.
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2006-09-29
- Volume
- 63
- Issue
- 19-20
- Pages
- 2415-2425
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC11136287
- OpenAlex
- W2109828316
- Cited by
- 263
- References
- 46
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 6 · 2023: 14 · 2022: 6 · 2021: 15 · 2020: 14 · 2019: 18 · 2018: 19 · 2017: 19 · 2016: 20 · 2015: 14 · 2014: 12 · 2013: 13 · 2012: 11
- FWCI
- 6.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- edoc (University of Basel) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- statins, mitochondrial toxicity, skeletal muscle mitochondria, cerivastatin, fluvastatin, atorvastatin, simvastatin, pravastatin, L6 cells, mitochondrial membrane potential, state 3 respiration, respiratory control ratio, fatty acid beta-oxidation, mitochondrial swelling, cytochrome c release, DNA fragmentation, drug-induced cell death
- MeSH terms
- Atorvastatin, Fluvastatin, Animals, Fatty Acids, Fatty Acids, Monounsaturated, Heptanoic Acids, Indoles, Membrane Potentials, Mitochondria, Muscle, Oxygen, Pyridines, Pyrroles, Pravastatin, Apoptosis, Muscle, Skeletal, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, Cytochromes c, Mitochondrial Membranes, Rats, DNA Fragmentation
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