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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 1420892, 11 pages
https://doi.org/10.1155/2017/1420892
Research Article

Effects of Novel Nitric Oxide-Releasing Molecules against Oxidative Stress on Retinal Pigmented Epithelial Cells

1Department of Drug Sciences, University of Catania, Catania, Italy
2Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania, Catania, Italy
3Inserm U955, Equipe 12, 94000 Créteil, France
4Université Paris Est, Faculté de Médecine, 94000 Créteil, France
5Center for Research in Ocular Pharmacology – CERFO, University of Catania, Catania, Italy

Correspondence should be addressed to Claudio Bucolo; ti.tcinu@olocub.oidualc

Received 29 June 2017; Accepted 27 August 2017; Published 12 October 2017

Academic Editor: Adrian Smedowski

Copyright © 2017 Valeria Pittalà et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Oxidative stress is a hallmark of retinal degenerations such as age-related macular degeneration and diabetic retinopathy. Enhancement of heme oxygenase-1 (HO-1) activity in the retina would exert beneficial effects by protecting cells from oxidative stress, therefore promoting cell survival. Because a crosstalk exists between nitric oxide (NO) and HO-1 in promotion of cell survival under oxidative stress, we designed novel NO-releasing molecules also capable to induce HO-1. Starting from curcumin and caffeic acid phenethyl ester (CAPE), two known HO-1 inducers, the molecules were chemically modified by acylation with 4-bromo-butanoyl chloride and 2-chloro-propanoyl chloride, respectively, and then treated in the dark with AgNO3 to obtain the nitrate derivatives VP10/12 and VP10/39. Human retinal pigment epithelial cells (ARPE-19) subjected to H2O2-mediated oxidative stress were treated with the described NO-releasing compounds. VP10/39 showed significant () antioxidant and protecting activity against oxidative damage, in comparison to VP10/12, which in turn showed at 100 μM concentration a slight but significant cell toxicity. Only VP10/39 significantly () induced HO-1 in ARPE-19, most likely through covalent bond formation at Cys151 of the Keap1-BTB domain, as revealed from molecular docking analysis. In conclusion, the present data indicate VP10/39 as a promising candidate to protect ARPE-19 cells against oxidative stress.