Bicarbonate supplementation as a preventive way in statins-induced muscle damage.
OBJECTIVE
The aim of this study was to evaluate the bicarbonate-induced improvement of statins, cerivastatin, simvastatin acid and lovastatin acid -induced apoptosis using rat myoblast cell line (L6) as a model of in vitro skeletal muscle and of cerivastatin-induced muscle damage in vivo study.


METHODS
Statin-induced reduction of cell viability and apoptosis was measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay and caspase assay. In vivo, we evaluated plasma creatine phosphokinase (CPK) level in cerivastatin-treated rat.


RESULTS
Bicarbonate prevented cerivastatin-, simvastatin- acid and lovastatin acid -induced reduction of cell viability, morphological change and caspase activation in L6 cells. Moreover, in the in vivo study, bicarbonate prevented cerivastatin-induced increase in CPK concentrations.


CONCLUSIONS
These results from in vitro and in vivo studies support that bicarbonate supplementation prevented statin-induced muscle damage.
Kobayashi
Masaki
M
Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, Japan.
Kagawa
Toshiki
T
Narumi
Katsuya
K
Itagaki
Shirou
S
Hirano
Takeshi
T
Iseki
Ken
K
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology / Q000627:therapeutic use; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D008297:Male; D009135:Muscular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017693:Sodium Bicarbonate / Q000494:pharmacology* / Q000627:therapeutic use*
D001639:Bicarbonates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017693:Sodium Bicarbonate; D020169:Caspases