Captopril suppresses inflammation in endotoxin-induced uveitis in rats
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概要
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Captopril is an inhibitor of angiotensin-converting enzyme (ACE) that is largely used in the treatment of cardiovascular diseases. Several previous studies have demonstrated that captopril exhibits a wide variety of biological activities, including an anti-inflammatory action, on which we focused our attention. The aim of the present study was to investigate the efficacy of captopril on endotoxin induced uveitis (EIU) in rats. We investigated its effect upon cellular infiltration and protein leakage, as well as on the concentration of tumor necrosis factor-α (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1) in the anterior chamber. In addition, we checked its effect on activation of nuclear factor kappa B (NF-κB) in iris and ciliary body (ICB) cells in vivo. EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). One hour after the LPS inoculation, either 1 mg/kg, 10 mg/kg or 100 mg/kg captopril were injected intravenously. 24 h later, the aqueous humor was collected from both eyes, and the number of infiltrating cells and protein concentration in the aqueous humor were determined. Levels of TNF-α, PGE2, NO and MCP-1 were determined by enzyme-linked immunosorbent assay. On some eyes, after enucleation, immunohistochemical staining with a monoclonal antibody against activated NF-κB was performed. Captopril treatment significantly decreased the inflammatory cells infiltration, the level of protein, concentrations of TNF-α, PGE2, NO and MCP-1 in the aqueous humor. The number of activated NF-κB-positive cells was lower in ICB of the rats treated with captopril 3 h after the LPS injection. The present results indicate that captopril suppresses the inflammation in EIU by inhibiting the NF-κB-dependent pathway and the subsequent production of pro-inflammatory mediators.
- Elsevier B.V.の論文
著者
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Ohno Shigeaki
北海道大学 大学院医学研究科感覚器病学講座眼科学分野
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Kase Satoru
Department Of Ophthalmology Hokkaido University Graduate School Of Medicine
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Ohno Shigeaki
Department Of Ocular Inflammation And Immunology Hokkaido University Graduate School Of Medicine
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Ohno Shigeaki
Department Of Ophthalmology And Visual Sciences Hokkaido University Graduate School Of Medicine
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Ohno S
Department Of Ocular Inflammation And Immunology Hokkaido University Graduate School Of Medicine
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Kase Satoru
Department Of Ophthalmology And Visual Sciences Hokkaido University Graduate School Of Medicine
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