Antioxidant treatment of experimental diabetic retinopathy in rats with nicanartine.
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; HbA1 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; HbA1 11.5 +/- 1.5%) and untreated, non-diabetic rats (n = 8; blood glucose 4.0 +/- 0.6 mmol/l; HbA1 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.
Hammes
H P
HP
III Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany.
Bartmann
A
A
Engel
L
L
Wülfroth
P
P
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004790:Enzyme Induction; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D051547:Heme Oxygenase-1; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*
D000975:Antioxidants; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D011725:Pyridines; C100546:nicanartine