Peroxynitrite decomposition catalyst, FP15, and poly(ADP-ribose) polymerase inhibitor, PJ34, inhibit leukocyte entrapment in the retinal microcirculation of diabetic rats

Current Eye Research
R SugawaraC Szabo

Abstract

Oxidative and nitrosative stress and activation of poly(ADP ribose) polymerase (PARP) play a role in the pathogenesis of diabetic complications. We evaluated the effectiveness of the peroxynitrite decomposition catalyst, FP15, and the PARP inhibitor, PJ34, in the treatment of leukocyte entrapment in the retinal microcirculation of diabetic rats. Diabetes was induced in rats by intraperitoneal injection of 60 mg/kg of streptozotocin. Rats were divided into four groups: controls; untreated diabetes; diabetes treated with FP15 (10 mg/kg oral gavage twice daily) and diabetes treated with PJ34 (10 mg/kg oral gavage twice daily). All experiments were performed 4 weeks after initiation of treatment. Leukocyte entrapment in the retinal microcirculation was quantitatively evaluated in vivo with acridine orange digital fluorography. The density of leukocytes trapped in the retinal microcirculation 30 minutes after dye injection was significantly greater in untreated diabetes (32.1 +/- 4.7 cells/mm2) than in controls (11.3 +/- 4.5 cells/mm2) (p < 0.05). Compared with untreated diabetes, the density of trapped leukocytes significantly decreased in diabetes treated with FP15 (14.5 +/- 5.1 cells/mm2) (p < 0.0001) and diabetes treated with PJ...Continue Reading

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Citations

Apr 27, 2013·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Mohd Imtiaz NawazMohammad Shamsul Ola
Mar 8, 2013·Future Medicinal Chemistry·Megha BarotAshim K Mitra
Dec 19, 2013·Mediators of Inflammation·Ghulam MohammadAhmed M Abu El-Asrar
Jan 13, 2015·Expert Opinion on Therapeutic Patents·Lauren M Slosky, Todd W Vanderah
Feb 13, 2009·British Journal of Pharmacology·Csaba Szabo
Aug 8, 2015·Biochimica Et Biophysica Acta·Renu A Kowluru, Manish Mishra
May 16, 2015·Progress in Retinal and Eye Research·Renu A KowluruBinit Kumar
Nov 6, 2010·Experimental Diabetes Research·Azza B El-RemessyR William Caldwell
Feb 2, 2013·Molecular Aspects of Medicine·Nicola J Curtin, Csaba Szabo
Jan 30, 2014·International Journal of Molecular Sciences·Andrew J PaynePeter Koulen
Aug 2, 2007·Nature Reviews. Drug Discovery·Csaba SzabóRafael Radi
Jul 26, 2008·Reviews in Endocrine & Metabolic Disorders·Sally A Madsen-Bouterse, Renu A Kowluru

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