Publications by authors named "Hiroko Moroe"

4 Publications

  • Page 1 of 1

Protective effects of NSP-116, a novel imidazolyl aniline derivative, against light-induced retinal damage in vitro and in vivo.

Free Radic Biol Med 2016 07 2;96:304-12. Epub 2016 May 2.

Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Japan. Electronic address:

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).
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http://dx.doi.org/10.1016/j.freeradbiomed.2016.03.036DOI Listing
July 2016

Comparison of endothelial function in the carotid artery between normal and short-term hypercholesterolemic rabbits.

Comp Biochem Physiol C Toxicol Pharmacol 2006 Oct 3;144(2):197-203. Epub 2006 Sep 3.

Second Department of Physiology, School of Medicine, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo, 142-8555, Japan.

The present study was undertaken to investigate and compare the vascular function in carotid arteries isolated from normal short-term hypercholesterolemic rabbits. Rabbits were fed normal or 0.5% cholesterol chow for 5 weeks. The tension of isolated carotid artery rings was measured isometrically. Serum lipid levels were measured and morphometric analysis was performed. And content of nitrate/nitrite in the carotid artery was also determined. In the carotid artery precontracted by phenylephrine, the cholesterol chow diet administered for 5 weeks decreased acetylcholine-induced relaxation at only middle concentrations, though it significantly increased the content of nitrate/nitrite, the sum of stable nitric oxide metabolites, in the carotid artery. Cholesterol chow for 5 weeks had no influence on sodium nitroprusside-induced relaxation in the carotid artery. The N(G)-nitro-L-arginine- and indomethacin-resistant endothelium-dependent relaxation induced by acetylcholine was significantly decreased in rabbits receiving the cholesterol chow as compared to rabbits receiving the control diet. The resistant part of acetylcholine-induced relaxation was significantly inhibited when the carotid artery was treated with glibenclamide, a selective inhibitor of ATP-sensitive K(+) channels, 4-aminopyridine, an inhibitor of voltage-dependent K(+) channels, or charybdotoxin, an inhibitor of large and intermediate conductance Ca(2+)-activated K(+) channels, and it was significantly inhibited by tetraethylammonium, a non-selective inhibitor of Ca(2+)-activated K(+) channels and N,N-di-ethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525a), a nonselective cytochrome P-450 monooxygenase (CYP) inhibitor, or ketoconazole, a selective CYP3A inhibitor in only normal rabbits. These results suggest that short-term hypercholesterolemia decreased EDHF-induced relaxation mediated through K(+) channels in rabbit carotid artery and that it may be due partially to the inhibition of CYP3A system in the carotid artery at an early stage of hypercholesterolemia.
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http://dx.doi.org/10.1016/j.cbpc.2006.08.011DOI Listing
October 2006

Hypothyroidism changes adrenoceptor- and muscarinic receptor-mediated blood pressure responses.

Eur J Pharmacol 2005 Jan 23;507(1-3):311-6. Epub 2004 Nov 23.

Second Department of Physiology, School of Medicine, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8555, Japan.

Hypothyroidism was induced by the administration of 0.03% methimazole to drinking water for 1, 2 or 6 weeks to study whether there is a change in adrenoceptor- and muscarinic receptor-mediated blood pressure responses in hypothyroid rats. After 1, 2 and 6 weeks of treatment, the pressor response to norepinephrine was progressively suppressed, and after 6 weeks a significant suppression was observed as compared to control. The depressor response induced by isoprenaline, acetylcholine or sodium nitroprusside was not significantly different between control and hypothyroid rats at any time. The pressor response induced by N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide (NO) synthase, was significantly reduced in hypothyroid rats after 1, 2 or 6 weeks of treatment, and the magnitude of the reduction was almost the same for three groups. These results indicated that hypothyroidism causes a time-dependent decrease in pressor responses mediated by alpha-adrenoceptors, but a time-independent decrease in those induced by L-NOARG, and suggest that a progressive decrease in alpha-adrenoceptor-mediated pressor responses occurs in hypothyroidism; however, the decrease in basal NO production and/or release in the peripheral vasculature already occurs in hypothyroid rats at an early stage of the disease.
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http://dx.doi.org/10.1016/j.ejphar.2004.11.002DOI Listing
January 2005

Characterization of endothelium-dependent relaxation and modulation by treatment with pioglitazone in the hypercholesterolemic rabbit renal artery.

Eur J Pharmacol 2004 Aug;497(3):317-25

Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

The present study was undertaken to investigate vascular function in hypercholesterolemic rabbits and also to characterize the effects of pioglitazone on it. Rabbits were fed normal, 0.5% cholesterol chow, or 0.5% cholesterol chow plus 300 ppm pioglitazone for 5 or 10 weeks. The tension of isolated renal artery rings was measured isometrically, and morphometric analysis was performed. The cholesterol chow diet administered for 5 weeks did not affect acetylcholine-induced relaxation in the renal artery but that for 10 weeks decreased it. The N(G)-nitro-L-arginine (L-NOARG)- and indomethacin-resistant endothelium-dependent relaxation induced by acetylcholine in the renal artery was enhanced in rabbits receiving the cholesterol chow for 5 or 10 weeks, as compared to rabbits receiving the control diet, and the percentage of plaque area formation was increased in the renal artery by the cholesterol chow for 10 weeks. Pioglitazone normalized them without lowering serum lipid levels. The resistant parts of acetylcholine-induced relaxation was significantly inhibited when the renal artery was treated with charybdotoxin, an inhibitor of large and intermediate conductance Ca(2+)-activated K(+) channels, or N,N-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525a), a cytochrome P-450 monooxygenase inhibitor. Results indicate that hypercholesterolemia enhances endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in the rabbit renal artery and pioglitazon normalizes it without lowering serum lipid levels, and suggest that the maintenance of endothelial function by pioglitazon is related to the mechanisms for its anti-atheromatous activity.
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http://dx.doi.org/10.1016/j.ejphar.2004.06.062DOI Listing
August 2004
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