Effects of Acidification and Alkalinization Agent on Statins-induced Muscle Toxicity

作者：Kobayashi Masaki; Hidaka Kazuhiro; Chisaki Ikumi; Takahashi Natsuko; Ogura Jiro; Itagaki Shirou; Hirano Takeshi; Yamaguchi Hiroaki; Iseki Ken^*

来源：Journal of the Pharmaceutical Society of Japan, 2012, 132(5): 609-615.

DOI：10.1248/yakushi.132.609

• statin
• muscle toxicity
• alpha-cyano-4-hydroxycinnamic acid
• citrate

The aim of this study was to determine the effects of alpha-cyano-4-hydroxycinnamic acid (CHC), a lactate efflux inhibitor, and citrate, an alkaline reagent, on statin-induced muscle injury using a human prototypic embryonal rhabdomyosarcoma cell line (RD) as a model of in vitro skeletal muscle and on statin-induced muscle damage in an in vivo study. Statin-induced reduction of cell viability and apoptosis was measured by the 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay and caspase assay. In an in vivo study, plasma creatine phosphokinase (CPK) level was examined in cerivastatin-treated rats. CHC increased growth inhibition of RD cells induced by cerivastatin, a lipophilic statin, but not these induced by pravastatin, a hydrophilic statin. On the other hand, citrate suppressed cerivastatin-, simvastatin- and atorvastatin-induced reduction of cell viability and caspase activation in RD cells. Moreover, citrate prevented cerivastatin-induced increase in CPK concentration in a concentration-dependent manner. This is first study to evaluate CHC or citrate-induced exacerbation or improvement of statin-induced muscle damage.

• 出版日期2012-5