Calcium dobesilate attenuates vascular injury and the progression of diabetic retinopathy in streptozotocin-induced diabetic rats.
BACKGROUND
Diabetic retinopathy (DR) is a highly specific vascular complication of type 1 and type 2 diabetes mellitus. Calcium dobesilate (DOBE) has been tested in the treatment of diabetic retinopathy showing a slowdown of the progression of the disease after long-term oral treatment. The aim of this study was to determine the effects of DOBE on vascular and diabetic retinopathy in streptozotocin (STZ) diabetic rats.


METHODS
Diabetes was induced in wistar rats by the administration of STZ (60 mg/kg, i.p.). Rats were divided into three groups (n = 30). Group 0 (GO): nondiabetic rats. Group 1 (G1): 14 months of insulin treatment after diabetes development. Group 2 (G2): 14 months of insulin treatment after diabetes development plus DOBE (500 mg/kg/day). At the end of the treatment, vascular reactivity was tested. The study of the vascularization of the retina was performed on wholemounts of trypsin retinal digest preparations and retinal sections.


RESULTS
Relaxation induced by acetylcholine decreased in the aorta arteries from diabetic rats but it was restored to control values in the DOBE-treated group (71.8 +/- 4.5%, 53.3 +/- 0.5%, 67.4 +/- 4.6% in group 0, 1 and 2 respectively). DOBE treatment also restored noradrenaline (1.08 +/- 0.05 g, 1.70 +/- 0.08 g, 1.13 +/- 0.05 g in group 0, 1 and 2 respectively) and caffeine-induced contractions. Diabetic state did not cause any alteration in mesenteric arteries. The analysis of the retinal digests showed vascular tortuosity, acellular capillaries, focal accumulations of capillaries and reduction of the number of pericytes in G1. The vascular changes observed in G2 seem to be intermediate between the control and the diabetic rats.


CONCLUSIONS
We showed that long-term treatment with DOBE attenuated the progression of diabetic retinopathy and the alterations in vascular reactivity in streptozotocin-induced diabetic rats.
Padilla
Eugenia
E
Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
Ganado
Patricia
P
Sanz
Mercedes
M
Zeini
Miriam
M
Ruiz
Emilio
E
Triviño
Alberto
A
Ramírez
Ana I
AI
Salazar
Juan J
JJ
Ramírez
Jose M
JM
Rojas
Blanca
B
Hoz
Rosa de
Rd
Tejerina
Teresa
T
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002123:Calcium Dobesilate / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D018450:Disease Progression; D006490:Hemostatics / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects / Q000293:injuries* / Q000473:pathology
D001786:Blood Glucose; D006490:Hemostatics; D002123:Calcium Dobesilate