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

• Kobayashi Masaki

  Laboratory of Clinical Pharmaceutics and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University

• Hidaka Kazuhiro

  Laboratory of Clinical Pharmaceutics and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University

• Chisaki Ikumi

  Laboratory of Clinical Pharmaceutics and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University

• Takahashi Natsuko

  Graduate School of Medicine, Hokkaido University

• Ogura Jiro

  Laboratory of Clinical Pharmaceutics and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University

• Itagaki Shirou

  Laboratory of Clinical Pharmaceutics and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University

• Hirano Takeshi

  Laboratory of Clinical Pharmaceutics and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University

• Yamaguchi Hiroaki

  Laboratory of Clinical Pharmaceutics and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University

• Iseki Ken

  Laboratory of Clinical Pharmaceutics and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University

Bibliographic Information

Other Title

• スタチンの骨格筋障害に及ぼす酸・アルカリ化誘導剤の影響
• スタチン ノ コッカクキン ショウガイ ニ オヨボス サン ・ アルカリカ ユウドウザイ ノ エイキョウ

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.<br>

Journal

• YAKUGAKU ZASSHI

  YAKUGAKU ZASSHI 132 (5), 609-615, 2012-05-01

  The Pharmaceutical Society of Japan

Keywords

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

Details

• CRID: 1390001206126659200
• NII Article ID: 130001888677
• NII Book ID: AN00284903
• DOI: 10.1248/yakushi.132.609
• COI: 1:STN:280:DC%2BC38jgslKnsw%3D%3D
• ISSN: 13475231
• ISSN: 00316903
• NDL BIB ID: 023754106
• PubMed: 22687697
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I023754106
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/132/5/132_5_609/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2012238653
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed