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 inhibito rs for the treatment of hypercholesterolemia is the development of myo sitis and, in some patients undergoing concomitant immunosuppressive t reatment, the development of rhabdomyolysis. Experiments outlined in t hese studies demonstrate that inhibitors of HMG-CoA reductase activity which differ primarily in the substitution of a methyl group for a hy droxyl group have differential effects on both cholesterol levels and cell viability in a striated muscle cell model, the mouse C-2-C-12 myo brast. Thus, concentrations as high as 200 mu M of pravastatin had lit tle effect on total cholesterol level while 25 mu M of lovastatin decr eased cellular cholesterol by over 90%. Simvastatin and lovastatin dec reased 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 almos t 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 t he effects on cell viability was simvastatin>lovastatin>>>pravastatin. The possible relationship between effects on cell viability and the d evelopment of myositis is discussed. (C) 1995 Academic Press Limited