Antioxidant Effects of Photodegradation Product of Nifedipine

Yuya Horinouchi; Koichiro Tsuchiya; Chiaki Taoka; Soichiro Tajima; Yoshitaka Kihira; Yuko Matsuda; Kozo Shishido; Masahiro Yoshida; Shuichi Hamano; Kazuyoshi Kawazoe; Yasumasa Ikeda; Keisuke Ishizawa; Shuhei Tomita; Toshiaki Tamaki

doi:10.1248/cpb.59.208

Regular Articles

Antioxidant Effects of Photodegradation Product of Nifedipine

Yuya Horinouchi, Koichiro Tsuchiya, Chiaki Taoka, Soichiro Tajima, Yoshitaka Kihira, Yuko Matsuda, Kozo Shishido, Masahiro Yoshida, Shuichi Hamano, Kazuyoshi Kawazoe, Yasumasa Ikeda, Keisuke Ishizawa, Shuhei Tomita, Toshiaki Tamaki

著者情報

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

キーワード: nifedipine, nitrosonifedipine, antioxidant, electron paramagnetic resonance, reactive oxygen species, endothelial cell

ジャーナルフリー

2011 年 59 巻 2 号 p. 208-214

DOI https://doi.org/10.1248/cpb.59.208

詳細

抄録

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.

責任著者(Corresponding author)

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