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Jun Suzuki, Joan W. Miller, Lucia Sobrin, Demetrios G. Vavvas; Inhibitory Effect Of Aicar On Endotoxin-induced Uveitis In Rats. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2943.
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To investigate the anti-inflammatory effect of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), stimulator of AMP-activated protein kinase, in endotoxin-induced uveitis (EIU) in rats and to elucidate the underlying molecular mechanisms.
EIU was induced by subcutaneous injection of lipopolysaccharide (LPS) (200 υg) in Lewis rats. Treatment group received AICAR (50mg/kg, intraperioneally), 6 hours prior and at the same time as LPS injection. After 24 hours, clinical uveitis scores were measured and aqueous humor was analyzed for leukocytes/ml and protein concentration. Leukocyte adhesion in the retinal vasculature was also measured. In addition, protein levels in the aqueous humor and whole retina were determined by ELISA for C-C chemokine ligand (CCL)2/ monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-alfa and intercellular adhesion molecule (ICAM)-1.
EIU clinical severity was significantly reduced in AICAR treated animals (3.7 ± 0.7 vs 2.4 ± 0.6, p<0.01) as were inflammatory cell infiltration and protein concentration in aqueous humor (11.6 ± 14.7 vs 1.5 ± 1.6x105 cells/ml; 17.8 ± 10.4 vs 7.8 ± 6.7 mg/ml, respectively, p<0.05). Similarly, the number of leukocytes adherent to retinal vessels was reduced (1161.6 ± 243.6 vs 575.5 ± 248.5 cells/retina, p<0.001) and protein levels of TNF-alfa, CCL2/MCP-1 and ICAM-1 in aqueous humor and CCL2/MCP-1 and ICAM-1 levels in retina were suppressed with treatment with AICAR.
AICAR attenuates EIU progression by limiting infiltration of leukocytes and suppressing the production of inflammatory cytokines.
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