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Toxicity of statins on rat skeletal muscle mitochondria

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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 μmol/l) induced death in 27–49% of the cells. Pravastatin was not toxic up to 1 mmol/l. Cerivastatin, fluvastatin and atorvastatin (100 μmol/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 μmol/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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Correspondence to S. Krähenbühl.

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Received 21 May 2006; received after revision 28 July 2006; accepted 25 August 2006

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Kaufmann, P., Török, M., Zahno, A. et al. Toxicity of statins on rat skeletal muscle mitochondria. Cell. Mol. Life Sci. 63, 2415–2425 (2006).

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