title: Inhibition of ocular aldose reductase by a new benzofuroxane derivative ameliorates rat endotoxic uveitis.
abstract: 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.
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Di Filippo
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors.forename: M V
authors.initials: MV
authors.lastname: Zippo
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Maisto
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Trotta
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Siniscalco
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Ferraro
authors.affiliation: Department of Clinical, Public and Preventive Medicine, Second University of Naples, Via Armanni 5, 80138 Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ferraraccio
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: La Motta
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sartini
authors.affiliation: DiSTABiF, Second University of Naples, Via Vivaldi 43, 81100 Caserta, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cosconati
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via Montesano 49, 80131 Naples, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Novellino
authors.affiliation: Multidisciplinary Department of Medical, Surgical and Dental Specialities, Second University of Naples, Via Pansini 5, 80131 Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Gesualdo
authors.affiliation: Multidisciplinary Department of Medical, Surgical and Dental Specialities, Second University of Naples, Via Pansini 5, 80131 Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Simonelli
authors.affiliation: Multidisciplinary Department of Medical, Surgical and Dental Specialities, Second University of Naples, Via Pansini 5, 80131 Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Amico
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005123:Eye / Q000201:enzymology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D014605:Uveitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C000599765:5(6)-(benzo(d)thiazol-2- ylmethoxy)benzofuroxane; D000975:Antioxidants; D001572:Benzofurans; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D025801:Ubiquitin; C002744:3-nitrotyrosine; D014443:Tyrosine; D000449:Aldehyde Reductase; D046988:Proteasome Endopeptidase Complex