PMID- 16698015
OWN - NLM
STAT- MEDLINE
DCOM- 20061106
LR  - 20220317
IS  - 0014-4835 (Print)
IS  - 0014-4835 (Linking)
VI  - 83
IP  - 3
DP  - 2006 Sep
TI  - Captopril suppresses inflammation in endotoxin-induced uveitis in rats.
PG  - 651-7
AB  - 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.
FAU - Ilieva, Iliyana
AU  - Ilieva I
AD  - Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate 
      School of Medicine, N15 W7 Kita-ku, Sapporo 060-8638, Japan. achibobo@yahoo.com
FAU - Ohgami, Kazuhiro
AU  - Ohgami K
FAU - Jin, Xue-Hai
AU  - Jin XH
FAU - Suzuki, Yukari
AU  - Suzuki Y
FAU - Shiratori, Kenji
AU  - Shiratori K
FAU - Yoshida, Kazuhiko
AU  - Yoshida K
FAU - Kase, Satoru
AU  - Kase S
FAU - Ohno, Shigeaki
AU  - Ohno S
LA  - eng
PT  - Journal Article
DEP - 20060512
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitrites)
RN  - 9G64RSX1XD (Captopril)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Aqueous Humor/chemistry
MH  - Captopril/*therapeutic use
MH  - Chemokine CCL2/analysis
MH  - Depression, Chemical
MH  - Dinoprostone/analysis
MH  - Immunohistochemistry/methods
MH  - Lipopolysaccharides
MH  - Male
MH  - Models, Animal
MH  - NF-kappa B/analysis
MH  - Nitrites/analysis
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Uvea/drug effects/*immunology/microbiology
MH  - Uveitis/*drug therapy/immunology/microbiology
EDAT- 2006/05/16 09:00
MHDA- 2006/11/07 09:00
CRDT- 2006/05/16 09:00
PHST- 2006/01/10 00:00 [received]
PHST- 2006/02/27 00:00 [revised]
PHST- 2006/03/05 00:00 [accepted]
PHST- 2006/05/16 09:00 [pubmed]
PHST- 2006/11/07 09:00 [medline]
PHST- 2006/05/16 09:00 [entrez]
AID - S0014-4835(06)00189-8 [pii]
AID - 10.1016/j.exer.2006.03.005 [doi]
PST - ppublish
SO  - Exp Eye Res. 2006 Sep;83(3):651-7. doi: 10.1016/j.exer.2006.03.005. Epub 2006 May 
      12.