Statin-induced myotoxicity is exacerbated by aging: A biophysical and molecular biology study in rats treated with atorvastatin

摘要: Statin-induced skeletal muscle damage in rats is associated to the reduction of resting sarcolemmal chloride conductance (gCl) and ClC-1 channel expression. These drugs also affect regulation by increasing protein kinase C (PKC) activity, which phosphorylate close channel. Also intracellular calcium (restCa) level increased. Similar alterations are observed muscles aged rats, suggesting a higher risk statin myotoxicity. To verify this hypothesis, we performed 4-5-weeks atorvastatin treatment 24-months-old evaluate function two-intracellular microelectrodes technique as well transcript expression different genes sensitive statins quantitative real-time-PCR western blot analysis. The restCa was measured using FURA-2 imaging, histological analysis sections performed. results show marked gCl, agreement with reduced mRNA atorvastatin-treated respect treated adult animals. changes myocyte-enhancer factor-2 (MEF2) may be involved changes. activity PKC increased further modulate gCl rats. In parallel, glycolytic mitochondrial enzymes demonstrates an impairment metabolism. No worsening or features found statin-treated findings suggest that strong alteration metabolism coupled atrophy contribute statin-induced myopathy elderly.