Abstract
Abstract: :
Purpose: To determine an anti-inflammatory role of atorvastatin on a standardizad model of eye inflammation, endotoxin-induced uveitis (EIU) in hypercholesterolemic rabbits (HChR). Methods: New Zealand White rabbits (3,5-4 kg) were fed with 0.5% cholesterol for 8 weeks. Atorvaststin (Park-Davis) was given to HChR (HChAR) and control rabbits (CAR) during the last 4 weeks of the diet as 2,5 or 5 mg/Kg/day. A control group was aslo included (CR). At the end of the treament, rabbits were injected intravitreal with 62,5 ng E.coli endotoxin 055:B5. Slit-lamp observations and aqueuos humor (AH) was harvested after 24 h. The levels of nitric oxide (NO) were measured by Griess' colorimetric assay, total proteins (TP), Prostaglandi-E2 by Elisa, and IL-6 activity by B9 bioassay. Cholesterol levels were determined by colorimetric assay. Atherosclerotic lesions were determined in iris and thoracic aortas. Results: The slit-lamp observation showed an improved of the iris inflammatory process of those groups of rabbits treated with atorvastatin for 4 weeks, although the cell inflitration was still strong in all groups of rabbits. The AH meansSE NO levels in EIU HChR (24.84.4 µM,n=5) were significantly reduced (p≷0.002) by atorvastatin (2,5 mg/kg/day) compared with HChAR (11.31.4 µM,n=6), which levels were not stastisticaly different from CR (8.31.5 µM,n=6). No difference were observed in IL-6, TP and PG-E2 levels between groups. When 5 mg/kg/day of atorvastatin was used, NO levels were not significantly reduced (p<0.123) in HChR (173.0480.3 µM,n=5) compared to HChAR (63.4171.5 µM,n=6), but were significantly compared to CR (8.2 1.6µM,n=6) (p≷0.002) or to CAR (3.160.5µM,n=4) (p≷0.007). No differences were observed for this dose in relation to PG-E2 and TP between experimental groups. The percentage of lesioned area in 2,5 mg/kg/day group was 57.8% (n=3) in HChR compared to 0% (n=3) in CR, 17.9% (n=3) HChAR and 0% (n=3) CAR. The percentage of iris lesioned area was 62.28% in HChR compared to 0% in CR, 36,12% HChAR and 0% (n=3) CAR. Conclusion: This data indicate that the reduction in NO levels induced by atorvastatin can produce a softer inflammatory process in iris tissue induced by endotoxin but not leukocyte migration. Longer treatments should be use in order to verify a role in leukocyte migration into the eye during atherosclerosis/hypercholesterolemia conditions after EIU.
Keywords: 612 uveitis-clinical/animal model • 458 lipids • 491 nitric oxide