Decreased ubiquinone availability and impaired mitochondrial cytochrome oxidase activity associated with statin treatment.
Toxicol Mech Methods
; 19(1): 44-50, 2009 Jan.
Article
em En
| MEDLINE
| ID: mdl-19778232
ABSTRACT
In order to investigate the potential involvement of mitochondrial electron transport chain (ETC) dysfunction in myotoxicity associated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) treatment, assessment was made of ETC activity and ubiquinone status in two patients experiencing myopathy following treatment with simvastatin (40 mg/day) and cyclosporin (patient 1) and simvastatin (40 mg/day) and itraconazole (patient 2). Analysis of skeletal muscle biopsies revealed a decreased ubiquinone status (77 and 132; reference range 140-580 pmol/mg) and cytochrome oxidase (complex IV) activity (0.006 and 0.007 reference range 0.014-0.034). To assess statin treatment in the absence of possible pharmacological interference from cyclosporin or itraconazole, primary astrocytes were cultured with lovastatin (100 microM). Lovastatin treatment resulted in a decrease in ubiquinone (97.9 +/- 14.9; control 202.9 +/- 18.4 pmol/mg; p < 0.05), and complex IV activity (0.008 +/- 0.001; control 0.011 +/- 0.001; p < 0.05) relative to control. These data, coupled with the patient findings, indicate a possible association between statin treatment, decreased ubiquinone status, and loss of complex IV activity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ubiquinona
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Complexo IV da Cadeia de Transporte de Elétrons
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Músculo Esquelético
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Inibidores de Hidroximetilglutaril-CoA Redutases
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Sinvastatina
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Doenças Musculares
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Revista:
Toxicol Mech Methods
Ano de publicação:
2009
Tipo de documento:
Article