title: Antioxidant effects of photodegradation product of nifedipine.
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.
authors.affiliation: Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Horinouchi
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Chiaki
authors.initials: C
authors.lastname: Taoka
authors.forename: Soichiro
authors.initials: S
authors.lastname: Tajima
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kihira
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Kozo
authors.initials: K
authors.lastname: Shishido
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yoshida
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hamano
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawazoe
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tomita
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009543:Nifedipine / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D016716:PC12 Cells; D010782:Photolysis / Q000187:drug effects; D051381:Rats
chemical_list: D000975:Antioxidants; D009543:Nifedipine