Antioxidant Effects of Photodegradation Product of Nifedipine

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Author(s)

    • Ishizawa Keisuke
    • Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima
    • Tomita Shuhei
    • Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima
    • Tamaki Toshiaki
    • Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima
    • Tsuchiya Koichiro
    • Department of Medical Pharmacology, The Institute of Health Bioscience, The University of Tokushima
    • Taoka Chiaki
    • Department of Medical Pharmacology, The Institute of Health Bioscience, The University of Tokushima
    • Tajima Soichiro
    • Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima
    • Kihira Yoshitaka
    • Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima
    • Matsuda Yuko
    • Department of Medical Pharmacology, The Institute of Health Bioscience, The University of Tokushima
    • Shishido Kozo
    • Department of Synthetic Organic Chemistry, The Institute of Health Bioscience, The University of Tokushima
    • Yoshida Masahiro
    • Department of Synthetic Organic Chemistry, The Institute of Health Bioscience, The University of Tokushima
    • Hamano Shuichi
    • Department of Pathological Science and Technology, The Institute of Health Bioscience, The University of Tokushima

Abstract

Recently, increasing evidence suggests that the antihypertensive drug nifedipine acts as a protective agent for endothelial cells, and that the activity is unrelated to its calcium channel blocking. Nifedipine is unstable under light and reportedly decomposes to a stable nitrosonifedipine (NO-NIF). NO-NIF has no antihypertensive effect, and it has been recognized as a contaminant of nifedipine. The present study for the first time demonstrated that NO-NIF changed to a NO-NIF radical in a time-dependent manner when it interacted with human umbilical vein endothelial cells (HUVECs). The electron paramagnetic resonance (EPR) signal of NO-NIF radicals in HUVECs showed an asymmetric pattern suggesting that the radicals were located in the membrane. The NO-NIF radicals had radical scavenging activity for 1,1-diphenyl-2-picrylhydrazyl, whereas neither NO-NIF nor nifedipine did. In addition, the NO-NIF radical more effectively quenched lipid peroxides than NO-NIF or nifedipine. Furthermore, NO-NIF attenuated the superoxide-derived free radicals in HUVECs stimulated with LY83583, and suppressed iron-nitrilotriacetic acid (Fe-NTA)-induced cytotoxicity in rat pheochromocytoma (PC12) cells. Our findings suggest that NO-NIF is a candidate for a new class of antioxidative drugs that protect cells against oxidative stress.

Journal

  • Chemical and Pharmaceutical Bulletin

    Chemical and Pharmaceutical Bulletin 59(2), 208-214, 2011

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130000405517
  • NII NACSIS-CAT ID (NCID)
    AA00602100
  • Text Lang
    ENG
  • ISSN
    0009-2363
  • NDL Article ID
    10951869
  • NDL Source Classification
    ZS51(科学技術--薬学) // ZP1(科学技術--化学・化学工業)
  • NDL Call No.
    Z53-D167
  • Data Source
    NDL  J-STAGE 
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