Captopril suppresses inflammation in endotoxin-induced uveitis in rats.
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-alpha (TNF-alpha), 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-kappaB) 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 1mg/kg, 10mg/kg or 100mg/kg captopril were injected intravenously. 24h 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-alpha, 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-kappaB was performed. Captopril treatment significantly decreased the inflammatory cells infiltration, the level of protein, concentrations of TNF-alpha, PGE2, NO and MCP-1 in the aqueous humor. The number of activated NF-kappaB-positive cells was lower in ICB of the rats treated with captopril 3h after the LPS injection. The present results indicate that captopril suppresses the inflammation in EIU by inhibiting the NF-kappaB-dependent pathway and the subsequent production of pro-inflammatory mediators.
Ilieva
Iliyana
I
Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, N15 W7 Kita-ku, Sapporo 060-8638, Japan. achibobo@yahoo.com
Ohgami
Kazuhiro
K
Jin
Xue-Hai
XH
Suzuki
Yukari
Y
Shiratori
Kenji
K
Yoshida
Kazuhiko
K
Kase
Satoru
S
Ohno
Shigeaki
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001082:Aqueous Humor / Q000737:chemistry; D002216:Captopril / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000032:analysis; D003864:Depression, Chemical; D015232:Dinoprostone / Q000032:analysis; D007150:Immunohistochemistry / Q000379:methods; D008070:Lipopolysaccharides; D008297:Male; D023421:Models, Animal; D016328:NF-kappa B / Q000032:analysis; D009573:Nitrites / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D014602:Uvea / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology
D000893:Anti-Inflammatory Agents; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D002216:Captopril; D015232:Dinoprostone