Y. Leung, J. Turgeon, V. Michaud; CRCHUM/Université de Montréal, Montreal, QC, CanadaBACKGROUND:
Statin-associated muscle symptoms are a common condition that affects 10-15% of patients. Lactic acid, mainly produced in muscle cells, is transported by the monocarboxylate transporters (MCT1 and 4). We hypothesized that statins affect the transport of lactic acid via MCTs leading to intracellular acidification in muscle cells and thus, induce muscle adverse events. The objective was to evaluate whether the statins can affect the lactic acid transport in human skeletal muscle cells (SkMC).METHODS:
Human primary myoblasts (Cell Applications Inc.) were grown and differentiated into SkMC with multinucleated syncytia. The inhibitory potential of statins on MCT-mediated transport of lactic acid were assessed: SkMC were incubated in a solution containing lactic acid [14C] (6mM) with or without statins (atorvastatin, cerivastatin, lovastatin acid, rosuvastatin and simvastatin acid: 5-200µM) for 2.5 min at 37°C. The intracellular concentration of radioactive lactic acid was measured by scintillation.RESULTS:
IC50 values are shown in the table.CONCLUSION:
Our data demonstrated that statins exhibit differential inhibitor activities on lactic acid transport through MCTs in SkMC. Further studies are required to relate the intracellular accumulation of lactic acid and statin-induced muscle disorders.
IC50 of statins for lactic acid transport
|Statins||IC50 - Uptake(µM)||IC50 - Efflux(µM)|