Differential sensitivity of C2-C12 striated muscle cells to lovastatin and pravastatin

AP Gadbut, AP Caruso, JB Galper - Journal of molecular and cellular …, 1995 - Elsevier
AP Gadbut, AP Caruso, JB Galper
Journal of molecular and cellular cardiology, 1995Elsevier
One of the major side-effects of the use of HMG CoA reductase inhibitors for the treatment of
hypercholesterolemia is the development of myositis and, in some patients undergoing
concomitant immunosuppressive treatment, the development of rhabdomyolysis.
Experiments outlined in these studies demonstrate that inhibitors of HMG-CoA reductase
activity which differ primarily in the substitution of a methyl group for a hydroxyl group have
differential effects on both cholesterol levels and cell viability in a striated muscle cell model …
One of the major side-effects of the use of HMG CoA reductase inhibitors for the treatment of hypercholesterolemia is the development of myositis and, in some patients undergoing concomitant immunosuppressive treatment, the development of rhabdomyolysis. Experiments outlined in these studies demonstrate that inhibitors of HMG-CoA reductase activity which differ primarily in the substitution of a methyl group for a hydroxyl group have differential effects on both cholesterol levels and cell viability in a striated muscle cell model, the mouse C2-C12 myoblast. Thus, concentrations as high as 200 μm of pravastatin had little effect on total cholesterol level while 25 μm of lovastatin decreased cellular cholesterol by over 90%. Simvastatin and lovastatin decreased viability of C2-C12 myoblasts by nearly 50% at concentrations as low as 1 and 5 μm, respectively, and decreased viability by almost 90% at 10 and 15 μ respectively. However, 300 μm of pravastatin decreased cell viability by less than 50%. The order of potency for the effects on cell viability was simvastatin>lovastatin>>>pravastatin. The possible relationship between effects on cell viability and the development of myositis is discussed.
Elsevier