RESEARCH ARTICLE
Aldose Reductase Inhibitor Fidarestat Prevents Diabetic Ocular Complications in Spontaneously Diabetic Torii Rats
Akihiro Kakehashi*, 1, Mikiko Takezawa1, Fumihiko Toyoda1, Nozomi Kinoshita1, Chiho Kambara1, Hiroko Yamagami1, Noriaki Kato2, San-e Ishikawa3, Masanobu Kawakami3, Yasunori Kanazawa4
Article Information
Identifiers and Pagination:
Year: 2011Volume: 4
First Page: 101
Last Page: 107
Publisher Id: TODIAJ-4-101
DOI: 10.2174/1876524601104010101
Article History:
Received Date: 16/04/2010Revision Received Date: 20/08/2010
Acceptance Date: 16/01/2011
Electronic publication date: 28/3/2011
Collection year: 2011
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
We evaluated the effect of an aldose reductase inhibitor, fidarestat, on diabetic retinopathy (DR) and cataract in spontaneously diabetic Torii (SDT) rats. Four rat groups were included: untreated, low- and high-dose (8 and 32 mg/kg/day) fidarestat-treated SDT rats, and nondiabetic control Sprague-Dawley rats. DR and cataract were evaluated and retinal and lens sorbitol, reduced glutathione (GSH), ocular fluid vascular endothelial growth factor (VEGF), and urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) was measured. The incidence rates of DR and cataract were significantly lower in the low- and high-dose fidarestat groups vs the untreated group (p<0.001/p<0.001). Retinal and lens sorbitol levels were lower in the control (1.1±0.1/3.1±0.2 nmol/mg protein) (p<0.05/p<0.01) and low- (2.7±1.1/30.0±3.3 nmol/mg protein) (p<0.01/p<0.01) and high-dose groups (0.7±0.2/5.9±0.6 nmol/mg protein) (p<0.001/p<0.001) vs the untreated group (23.2±4.7/123.9±29.6 nmol/mg protein). Retinal and lens GSH levels were higher in the nondiabetic control (52.2±5.8/29.0±2.7 mol/mg protein) (p<0.01/p<0.001) and the low- (46.8±8.2/24.7±2.8 mol/mg protein) (not significant (NS)/p<0.001) and high-dose groups (63.3±14.6/26.9±3.6 mol/mg protein) (p<0.05/p<0.001) vs the untreated group (30.3±2.0/1.6±0.4 mol/mg protein). VEGF levels were lower in the nondiabetic control (40.4±10.0 pg/ml) (p<0.01) and low- (65.3±4.5 pg/ml) (p<0.05) and high-dose groups (47.7±10 pg/ml) (p<0.001) vs the untreated group (324.7±76.4 pg/ml). 8-OHdG levels were lower in the nondiabetic control (0.73±0.11 ng/mg creatinine) (p<0.01) and low- (4.57±0.42 ng/mg creatinine) (NS) and high-dose groups (3.58±0.70 ng/mg creatinine) (NS) vs the untreated group (6.04±1.28 ng/ml). Fidarestat inhibited activation of the polyol pathway, reduced oxidative stress and VEGF, and prevented DR and cataract in SDT rats.