DIFFERENTIAL SENSITIVITY OF C-2-C-12 STRIATED-MUSCLE CELLS TO LOVASTATIN AND PRAVASTATIN

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 C-2-C-12 myobrast. Thus, concentrations as high as 200 mu M of pravastatin had little effect on total cholesterol level while 25 mu M of lovastatin decreased cellular cholesterol by over 90%. Simvastatin and lovastatin decreased viability of C-2-C-12 myoblasts by nearly 50% at concentrations as low as 1 and 5 mu M, respectively and decreased viability by almost 90% at 10 and 15 mu M respectively. However, 300 mu M 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. (C) 1995 Academic Press Limited