Toxicity of statins on rat skeletal muscle mitochondria

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. Pravastati...

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Published in:Cellular and molecular life sciences : CMLS 2006-10, Vol.63 (19-20), p.2415-2425
Main Authors: Kaufmann, P, Török, M, Zahno, A, Waldhauser, K M, Brecht, K, Krähenbühl, S
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Atorvastatin
Cytochromes c - metabolism
DNA Fragmentation - drug effects
Fatty Acids - metabolism
Fatty Acids, Monounsaturated - toxicity
Fluvastatin
Heptanoic Acids - toxicity
Hydroxymethylglutaryl-CoA Reductase Inhibitors - toxicity
Indoles - toxicity
Membrane Potentials - drug effects
Mitochondria
Mitochondria, Muscle - drug effects
Mitochondria, Muscle - ultrastructure
Mitochondrial Membranes - drug effects
Mitochondrial Membranes - physiology
Muscle, Skeletal - drug effects
Muscle, Skeletal - ultrastructure
Oxygen - metabolism
Pravastatin - toxicity
Pyridines - toxicity
Pyrroles - toxicity
Rats
Rodents
Simvastatin - toxicity
Skeletal system
Statins
Toxicity
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Summary: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.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-006-6235-z