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Mediators of Inflammation
Volume 2014, Article ID 857958, 9 pages
Research Article

Inhibition of Ocular Aldose Reductase by a New Benzofuroxane Derivative Ameliorates Rat Endotoxic Uveitis

1Department of Experimental Medicine, Section of Pharmacology “L. Donatelli”, Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy
2Department of Clinical, Public and Preventive Medicine, Second University of Naples, Via Armanni 5, 80138 Naples, Italy
3Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy
4DiSTABiF, Second University of Naples, Via Vivaldi 43, 81100 Caserta, Italy
5Department of Pharmacy, University of Naples “Federico II”, Via Montesano 49, 80131 Naples, Italy
6Multidisciplinary Department of Medical, Surgical and Dental Specialities, Second University of Naples, Via Pansini 5, 80131 Naples, Italy

Received 29 July 2014; Revised 15 October 2014; Accepted 21 October 2014; Published 11 November 2014

Academic Editor: Fumio Tsuji

Copyright © 2014 C. Di Filippo 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.


The study investigated the effects of the aldose reductase (AR) inhibitor benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy) benzofuroxane (herein referred to as BF-5m) on the biochemical and tissue alterations induced by endotoxic uveitis in rats. BF-5m has been administered directly into the vitreous, in order to assess the expression and levels of (i) inflammatory markers such as the ocular ubiquitin-proteasome system, NF-κB, TNF-α, and MCP-1; (ii) prooxidant and antioxidant markers such as nitrotyrosine, manganese superoxide dismutase (MnSOD), and glutathione peroxidase (GPX); (iii) apoptotic/antiapoptotic factors caspases and Bcl-xl; (iv) markers of endothelial progenitor cells (EPCs) recruitment such as CD34 and CD117. 5 μL of BF-5m (0.01; 0.05; and 0.1 μM) into the right eye decreased in a dose-dependent manner the LPS-induced inflammation of the eye, reporting a clinical score 1. It reduced the ocular levels of ubiquitin, 20S and 26S proteasome subunits, NF-κB subunits, TNF-α, MCP-1, and nitrotyrosine. BF-5m ameliorated LPS-induced decrease in levels of MnSOD and GPX. Antiapoptotic effects were seen from BF-5m by monitoring the expression of Bcl-xl, an antiapoptotic protein. Similarly, BF-5m increased recruitment of the EPCs within the eye, as evidenced by CD34 and CD117 antibodies.