ABSTRACT
To study the potential effect of simvastatin, a hypocholesterolemic drug, to induce myopathy with or without cyclosporin A, 36 rats were included. Rats were treated for one week peroid and were classified into 6 groups [6 rats each]. Group I [control group]; given 0.5 ml gum tragacanth suspension orally + 0.5 ml S.c. saline daily. Group II; given 50 mg/kg /day simvastatin in gum tragacanth orally + 0.5 ml S. C.saline. Group Ill; given 100 ml/kg/ day simvastatin in gum tragacanth orally + 0.5 ml S.c. saline. Group IV; given 50 mg/kg/daysimvastatin orally+ 10 mg/kg/day S.C. cyclosporin A. Group V; given 100 mg/kg/day simvastatin orally + 10 mg/kg/ day S.c. cyclosporin A. Group VI; given 10 mg/kg/ day S.C. cyclosporin A + 0.5 ml oral gum tragacanth daily. At the end of one week, blood samples were collected and the sera were assayed for total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and creatine.phosphokinase. Skeletal muscle specimens were dissected and were fixed either in 10% formal saline or in 3% gluteraldhyde in 0.1 M phosphate buffer [pH 7.3]. Specimens were processed and stained with HX.E and Van Gieson stains for light microscopic study and with uranyl acetate and lead citrate for electron microscopic study. Results showed that simvastatin in small dose [50 mg/kg] [G II] produced minor skeletal muscle changes evidenced by presence of cloudy swelling of the muscle fibers and mononuclear celullar infiltrates. However, large dose of simvastatin [100 mg/kg] [G Ill] was associated with more severe degenerative changes, inflammatory cell reaction and necrosis of the muscle fibers with mitochondrial darnage and multiple inclusion bodies. These changes were more evident with coadministration of cyclosporin A to either small or large doses simvastatin-treated rats [G IV and V]: The serum creatine phosphokinase levels were increased in all treated groups [G II to VI] compared with control group [G I]. The enzyme level reaches a significant degree only in the high dose combination group [G V] compared with conrtol group [1306.8 +/- 87.76 Vs 566.17 +/- 59.58 IU/L, P <0.05]. Thus, simvastatin can produce skeletal muscle damage in rat in short-term peroid.The myopathic changes were dose related.and were potentiated by concomitant use of cyclosporin A. It is recommended to extend the study for a longer period