[Effects of acidification and alkalinization agents on statins-induced muscle toxicity].

Abstract	The aim of this study was to determine the effects of α-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.
Authors	Masaki Kobayashi, Kazuhiro Hidaka, Ikumi Chisaki, Natsuko Takahashi, Jiro Ogura, Shirou Itagaki, Takeshi Hirano, Hiroaki Yamaguchi, Ken Iseki
Journal	Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan (Yakugaku Zasshi) Vol. 132 Issue 5 Pg. 609-15 ( 2012) ISSN: 1347-5231 [Electronic] Japan
PMID	22687697 (Publication Type: Journal Article)
Chemical References	Coumaric Acids Hydroxymethylglutaryl-CoA Reductase Inhibitors Pyridines Citric Acid cerivastatin Creatine Kinase Caspase 1
Topics	Animals Apoptosis (drug effects) Caspase 1 (metabolism) Cell Line, Tumor Cell Survival (drug effects) Cells, Cultured Citric Acid (pharmacology) Coumaric Acids (pharmacology) Creatine Kinase (blood) Humans Hydrogen-Ion Concentration Hydroxymethylglutaryl-CoA Reductase Inhibitors (adverse effects) Male Muscle, Skeletal (cytology, drug effects, pathology) Pyridines (adverse effects) Rats Rats, Wistar Rhabdomyosarcoma, Embryonal (enzymology, pathology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!