title: Protective effects of NSP-116, a novel imidazolyl aniline derivative, against light-induced retinal damage in vitro and in vivo.
abstract: In this study, we investigated the protective effects of NSP-116 [4-(4-acetylpiperazin-1-yl)-2-(1H-imidazol-1-yl) aniline], a novel imidazolyl aniline derivative, against light-induced photoreceptor cell damage. In an in vitro experiment, murine photoreceptor (661W) cells were damaged by exposure to light for 24h. Viability of 661W cells after light exposure was assessed by Hoechst 33342/Propidium iodide nuclear staining and a tetrazolium salt (WST-8) assay. Intracellular radical production in 661W cells was evaluated using the reactive oxygen species (ROS) sensitive probe 5-(and 6)-chloromethyl-2, 7-dichlorodihydrofluorescein diacetate acetyl ester (CM-H2DCFDA). NSP-116 significantly suppressed light-induced cell death and ROS production in 661W cells. In an in vivo mouse experiment, retinal damage was induced by exposure to white light at 8000lx for 3h after dark adaptation. Retinal damage was evaluated by recording the electroretinogram and measuring the outer nuclear layer (ONL) thickness at 5 days after light exposure. Single oral administration of NSP-116 before light exposure protected retinal function and ONL thinning after light exposure. Furthermore, the effect of NSP-116 on lipid peroxidation was evaluated using thiobarbituric acid reactive substance (TBARS) assay in porcine retina, and was found to decrease the production of TBARS. Electron spin resonance (ESR) measurements showed that NSP-116 exhibited radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide anion radical (∙O2(-)), and hydroxyl radical (∙OH). These findings suggest that NSP-116 has protective effects against light-induced photoreceptor degeneration in vitro and in vivo as a free radical scavenger, and it may be a novel therapeutic agent for retinal degenerative disorders, such as dry age-related macular degeneration (AMD).
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Izawa
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Odawara Research Center, Nippon Soda Co., Ltd, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Odawara Research Center, Nippon Soda Co., Ltd, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Moroe
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Japan. Electronic address: hidehara@gifu-pu.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D000814:Aniline Compounds / Q000008:administration & dosage*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D005452:Fluoresceins / Q000737:chemistry; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D007093:Imidazoles / Q000008:administration & dosage*; D008027:Light / Q000009:adverse effects; D051379:Mice; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000473:pathology; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013481:Superoxides / Q000378:metabolism
chemical_list: C110400:2',7'-dichlorodihydrofluorescein diacetate; C000625672:4-(4-acetylpiperazin-1-yl)-2-(1H-imidazol-1-yl)aniline; D000814:Aniline Compounds; D005452:Fluoresceins; D016166:Free Radical Scavengers; D007093:Imidazoles; D017382:Reactive Oxygen Species; D013481:Superoxides; D017665:Hydroxyl Radical
keywords: AMD; Free radical scavenger; Light, photoreceptor degeneration; NSP-116; Retina