Antioxidant treatment of experimental diabetic retinopathy in rats with nicanartine

被引:67
作者
Hammes, HP [1 ]
Bartmann, A [1 ]
Engel, L [1 ]
Wulfroth, P [1 ]
机构
[1] MERZ & CO,DEPT PHARMACOL,FRANKFURT,GERMANY
关键词
oxidant stress; nicanartine; diabetic retinopathy; rat; experimental;
D O I
10.1007/s001250050726
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In order to study the contribution of oxidant stress to the pathogenesis of experimental diabetic retinopathy, male streptozotocin diabetic Lewis rats were treated with the antioxidant and lipid-lowering compound nicanartine (80 mg/kg; n = 8, blood glucose level 16.7 +/- 3.9 mmol/l; HbA(1) 11.8 +/- 1.6 %) by oral supplementation for 6 months and compared with untreated diabetic (n = 6; blood glucose 18.1 +/- 1.4 mmol/l; HbA(1) 11.5 +/- 1.5 %) and untreated, nondiabetic rats (n = 8; blood glucose 4.0 +/- 0.6 mmol/l; HbA(1) 4.8 +/- 0.9 %). Diabetic retinopathy was evaluated by computer-assisted quantitative morphometry including measurement of autofluorescent advanced glycated end-products and immunohistochemistry for heme oxygenase I. Antioxidant treatment did not inhibit the 3.1-fold increase of retinal advanced glycation end products, while the expression of heme oxygenase I in both vascular and glial structures was markedly reduced. Chronic hyperglycaemia led to a 37.3 % increase in endothelial cells (p < 0.001 vs normal controls) and a 26.6 % reduction in pericyte numbers (p < 0.001 vs controls). Both abnormalities were significantly ameliorated by nicanartine (p < 0.001 vs diabetic controls). No effect was observed on the formation of acellular capillaries or microaneurysms. These data indicate that antioxidant therapy with nicanartine is of limited benefit in diabetic retinopathy, at least in the rodent model of streptozotocin-induced diabetes.
引用
收藏
页码:629 / 634
页数:6
相关论文
共 42 条
[11]  
Hammes HP, 1996, DIABETOLOGIA, V39, P251
[12]   AMINOGUANIDINE TREATMENT INHIBITS THE DEVELOPMENT OF EXPERIMENTAL DIABETIC-RETINOPATHY [J].
HAMMES, HP ;
MARTIN, S ;
FEDERLIN, K ;
GEISEN, K ;
BROWNLEE, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (24) :11555-11558
[13]  
HAMMES HP, 1996, DIABETES STOFFWECHSE, V5, pA136
[14]   LDL-INDUCED CYTOTOXICITY AND ITS INHIBITION BY HDL IN HUMAN VASCULAR SMOOTH-MUSCLE AND ENDOTHELIAL-CELLS IN CULTURE [J].
HESSLER, JR ;
ROBERTSON, AL ;
CHISOLM, GM .
ATHEROSCLEROSIS, 1979, 32 (03) :213-229
[15]   CATALYSIS OF LIPID-PEROXIDATION BY GLUCOSE AND GLYCOSYLATED COLLAGEN [J].
HICKS, M ;
DELBRIDGE, L ;
YUE, DK ;
REEVE, TS .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 151 (02) :649-655
[16]  
JIANG YZ, 1996, DIABETES MELLITUS, P719
[17]  
KADOR PF, 1985, ANNU REV PHARMACOL, V25, P691, DOI 10.1146/annurev.pa.25.040185.003355
[18]  
Kern T. S., 1996, Investigative Ophthalmology and Visual Science, V37, pS970
[19]   Abnormalities of retinal metabolism in diabetes or experimental galactosemia .3. Effects of antioxidants [J].
Kowluru, RA ;
Kern, TS ;
Engerman, RL ;
Armstrong, D .
DIABETES, 1996, 45 (09) :1233-1237
[20]   INDUCTION OF HEME OXYGENASE-1 IN THE RETINA BY INTENSE VISIBLE-LIGHT - SUPPRESSION BY THE ANTIOXIDANT DIMETHYLTHIOUREA [J].
KUTTY, RK ;
KUTTY, G ;
WIGGERT, B ;
CHADER, GJ ;
DARROW, RM ;
ORGANISCIAK, DT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (04) :1177-1181