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

R. Sugawara, Taiichi Hikichi, N. Kitaya, F. Mori, T. Nagaoka, A. Yoshida, Csaba Szabo

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Purpose. 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. Methods. Diabetes was induced in rats by intraperitoneal injection of 60mg/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. Results. 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 PJ34 (24.1 ± 4.2 cells/mm2) (p < 0.05). Conclusions. Treatment with FP15 and PJ34 decreased enhanced leukocyte entrapment in the retinal microcirculation during the early diabetic period. The current study suggests a role for peroxynitrite production and for PARP activation in the pathogenesis of retinal microvascular leukostasis in early diabetes.

Original languageEnglish (US)
Pages (from-to)11-16
Number of pages6
JournalCurrent Eye Research
Volume29
Issue number1
DOIs
StatePublished - Jul 2004
Externally publishedYes

Fingerprint

Peroxynitrous Acid
Microcirculation
Leukocytes
Poly(ADP-ribose) Polymerases
Photofluorography
Leukostasis
Acridine Orange
Diabetes Complications
Streptozocin
Intraperitoneal Injections
Oxidative Stress
Coloring Agents
Therapeutics
Poly(ADP-ribose) Polymerase Inhibitors
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
Control Groups
Injections

Keywords

  • Diabetic retinopathy
  • Leukocyte entrapment
  • Peroxynitrite decomposition catalyst
  • Poly(ADP ribose) polymerase inhibitor

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Peroxynitrite decomposition catalyst, FP15, and poly(ADP-ribose) polymerase inhibitor, PJ34, inhibit leukocyte entrapment in the retinal microcirculation of diabetic rats. / Sugawara, R.; Hikichi, Taiichi; Kitaya, N.; Mori, F.; Nagaoka, T.; Yoshida, A.; Szabo, Csaba.

In: Current Eye Research, Vol. 29, No. 1, 07.2004, p. 11-16.

Research output: Contribution to journalArticle

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title = "Peroxynitrite decomposition catalyst, FP15, and poly(ADP-ribose) polymerase inhibitor, PJ34, inhibit leukocyte entrapment in the retinal microcirculation of diabetic rats",
abstract = "Purpose. 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. Methods. Diabetes was induced in rats by intraperitoneal injection of 60mg/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. Results. 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 PJ34 (24.1 ± 4.2 cells/mm2) (p < 0.05). Conclusions. Treatment with FP15 and PJ34 decreased enhanced leukocyte entrapment in the retinal microcirculation during the early diabetic period. The current study suggests a role for peroxynitrite production and for PARP activation in the pathogenesis of retinal microvascular leukostasis in early diabetes.",
keywords = "Diabetic retinopathy, Leukocyte entrapment, Peroxynitrite decomposition catalyst, Poly(ADP ribose) polymerase inhibitor",
author = "R. Sugawara and Taiichi Hikichi and N. Kitaya and F. Mori and T. Nagaoka and A. Yoshida and Csaba Szabo",
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T1 - Peroxynitrite decomposition catalyst, FP15, and poly(ADP-ribose) polymerase inhibitor, PJ34, inhibit leukocyte entrapment in the retinal microcirculation of diabetic rats

AU - Sugawara, R.

AU - Hikichi, Taiichi

AU - Kitaya, N.

AU - Mori, F.

AU - Nagaoka, T.

AU - Yoshida, A.

AU - Szabo, Csaba

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N2 - Purpose. 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. Methods. Diabetes was induced in rats by intraperitoneal injection of 60mg/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. Results. 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 PJ34 (24.1 ± 4.2 cells/mm2) (p < 0.05). Conclusions. Treatment with FP15 and PJ34 decreased enhanced leukocyte entrapment in the retinal microcirculation during the early diabetic period. The current study suggests a role for peroxynitrite production and for PARP activation in the pathogenesis of retinal microvascular leukostasis in early diabetes.

AB - Purpose. 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. Methods. Diabetes was induced in rats by intraperitoneal injection of 60mg/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. Results. 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 PJ34 (24.1 ± 4.2 cells/mm2) (p < 0.05). Conclusions. Treatment with FP15 and PJ34 decreased enhanced leukocyte entrapment in the retinal microcirculation during the early diabetic period. The current study suggests a role for peroxynitrite production and for PARP activation in the pathogenesis of retinal microvascular leukostasis in early diabetes.

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KW - Poly(ADP ribose) polymerase inhibitor

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