Development of a method to attenuate the adverse effect of anti-arrhythmic bepridil

• Project/Area Number: 25460658
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Jichi Medical University
• Principal Investigator: Fujimura Akio 自治医科大学, 医学部, 教授 (90156901)
• Co-Investigator(Renkei-kenkyūsha): ANDO Hitoshi 金沢大学, 医学系, 教授 (50382875) ; KOSHIMIZU Takaaki 自治医科大学, 医学部, 准教授 (20392491) ; KAKEI Masafumi 自治医科大学, 医学部, 客員教授 (90214270) ; SHIGA Tsuyoshi 東京女子医科大学, 医学部, 准教授 (00277211)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 臨床薬理学 / 循環器 / 薬物有害反応 / QT延長

Outline of Final Research Achievements

Bepridil, an anti-arrhythmic drug, has beneficial clinical effects, but causes an adverse effect of QT prolongation leading to sudden cardiac death. In this study, we investigated the effects of alpha-lipoic acid (LA) on bepridil-induced QT prolongation, because LA can protect against arsenic trioxide-induced QT prolongation in guinea pigs. We found that LA dose-dependently attenuates bepridil-induced QT prolongation in guinea pigs, and that LA inhibits the formation of reactive oxygen species in H9c2 myocardial cells. Because alpha-tocopherol, an antioxidant, also attenuated bepridil-induced QT prolongation, LA appears to protect against the adverse effect at least through its antioxidant property.

Research Products

• [Journal Article] Influence of genetic polymorphisms of multidrug and toxin extrusion protein 1 on its mRNA expression in peripheral blood cells. (2016)
  • Author(s): Ando H, Nakano K, Ushijima K, Kurokawa S, Washino S, Hosohata K, Morita T, Fujimura A.
  • Journal Title: J Pharmacol Sci Volume: in press Issue: 2 Pages: 138-140
  • DOI: 10.1016/j.jphs.2016.03.002
  • Peer Reviewed / Open Access
• [Journal Article] Lipopolysaccharide-induced inflammation or unilateral ureteral obstruction yielded multiple types of glycosylated Lipocalin 2. (2016)
  • Author(s): Fujiwara Y, Tsuchiya H, Sakai N, Shibata K, Fujimura A, Koshimizu TA.
  • Journal Title: J Inflamm Volume: 13 Issue: 1 Pages: 7-7
  • DOI: 10.1186/s12950-016-0116-5
  • Peer Reviewed / Open Access
• [Journal Article] Early urinary biomarkers for renal tubular damage in spontaneously hypertensive rats on a high salt intake. (2016)
  • Author(s): Hosohata K, Yoshioka D, Tanaka A, Ando H, Fujimura A.
  • Journal Title: Hypertens Res Volume: 39 Issue: 1 Pages: 19-26
  • DOI: 10.1038/hr.2015.103
  • Peer Reviewed / Open Access
• [Journal Article] Influence of dioxin on the daily variation of insulin sensitivity in mice. (2015)
  • Author(s): Takuma M, Ushijima K, Kumazaki M, Ando H, Fujimura A.
  • Journal Title: Environ Toxicol Pharmacol Volume: 40 Pages: 349-351
  • Peer Reviewed
• [Journal Article] Association of decreased mRNA expression of multidrug and toxin extrusion protein 1 in peripheral blood cells with the development of flutamide-induced liver injury. (2015)
  • Author(s): Nakano K, Ando H, Kurokawa S, Hosohata K, Ushijima K, Takada M, Tateishi M, Yonezawa A, Masuda S, Matsubara K, Inui KI, Morita T, Fujimura A.
  • Journal Title: Cancer Chemother Pharmacol. Volume: ｉｎ ｐｒｅｓｓ Issue: 6 Pages: 1191-1197
  • DOI: 10.1007/s00280-015-2743-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant