Effect of thalidomide and rosiglitazone on the prevention of diabetic retinopathy in streptozotocin-induced diabetic rats.
OBJECTIVE
Our aim was to compare the therapeutic effect of thalidomide and rosiglitazone on the prevention of diabetic retinopathy in streptozotocin-induced diabetic rats.


METHODS
Male Holtzman rats of 6 to 8 weeks of age and weighing 170+/-30 g were randomly divided into four groups: control ( n=13), untreated diabetic ( n=17) and diabetic rats treated with thalidomide (200 mg kg(-1) day(-1)) ( n=8) or rosiglitazone (1 mg kg(-1) day(-1)) ( n=22) for 3 months. Diabetes was induced by streptozotocin with the rats having a body weight of 70 mg/kg. After treatment, vascular endothelial growth factor (VEGF) concentrations in ocular fluid were compared between the different groups, and retinal capillary basement membrane thickness was measured by electron microscopy.


RESULTS
Higher VEGF concentrations in ocular fluid and thicker basement membranes were observed in untreated diabetic rats compared to the control rats. Similar VEGF concentrations and basement membrane thickness were observed for the thalidomide-treated group compared with the control group, whereas no difference in these parameters was observed between the rosiglitazone-treated rats and the control or untreated diabetic rats.


CONCLUSIONS
Our findings confirm the association between VEGF concentrations and diabetic retinopathy as suggested by other investigators. Thalidomide, but not rosiglitazone, was associated with the inhibition of basement membrane thickening and the blockade of the increase of VEGF in ocular fluid, thus representing a potential therapeutic drug for the prevention of diabetic retinopathy.
Bosco
A A
AA
Endocrine Center Research of Santa Casa, Belo Horizonte and Laboratory of Medical Investigation (LIM 25), Hospital das Clinicas University of São Paulo, São Paulo, Brazil. a.bosco@terra.com.br
Lerario
A C
AC
Santos
R F
RF
Wajchenberg
B L
BL
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology* / Q000517:prevention & control*; D003930:Diabetic Retinopathy / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology; D000077154:Rosiglitazone; D013792:Thalidomide / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D042461:Vascular Endothelial Growth Factor A; D000077154:Rosiglitazone; D013792:Thalidomide