BACKGROUND: Angiogenic factors such as vascular endothelial growth factor (VEGF), erythropoietin, and angiopoietin play important roles in the pathophysiology of diabetic retinopathy. Increased amounts of reactive oxygen species (ROS) are also known to associated with diabetic retinopathy and VEGF expression. This study evaluated the effect of a simvastatin on ROS generation and the changes in various angiogenic factors in the retinas of diabetic rats. METHODS: The rats were divided into normal, diabetes mellitus (DM), and simvastatin-treated groups (each group, n = 10). Diabetes was induced by intraperitoneal injection of streptozotocin into 20 Sprague-Dawley rats. After diabetic induction, simvastatin (5mg/kg) was administered orally to ten rats. The expression levels of VEGF, erythropoietin, angiopoietin 1 and 2, and NADPH oxidase were examined in rat retinas by RT-PCR and Western blot. Superoxide formation was examined by dihydroethidium (DHE) staining. RESULTS: DHE analysis revealed increased superoxide formation in the retinas of the diabetic group, which was decreased in the group treated with simvastatin. Western blot analysis showed that NADPH oxidase levels were decreased in the diabetic group and remained normal in the simvastatin-treated group. Simvastatin treatment blocked hyperglycemia-induced increases in VEGF, angiopoietin 2 and erythropoietin levels, as demonstrated by RT-PCR and Western blot analysis. CONCLUSIONS: Simvastatin treatment led to suppression of superoxide formation and decreased expression of VEGF, angiopoietin 2 and erythropoietin in diabetic rat retinas.
BACKGROUND: Angiogenic factors such as vascular endothelial growth factor (VEGF), erythropoietin, and angiopoietin play important roles in the pathophysiology of diabetic retinopathy. Increased amounts of reactive oxygen species (ROS) are also known to associated with diabetic retinopathy and VEGF expression. This study evaluated the effect of a simvastatin on ROS generation and the changes in various angiogenic factors in the retinas of diabeticrats. METHODS: The rats were divided into normal, diabetes mellitus (DM), and simvastatin-treated groups (each group, n = 10). Diabetes was induced by intraperitoneal injection of streptozotocin into 20 Sprague-Dawley rats. After diabetic induction, simvastatin (5mg/kg) was administered orally to ten rats. The expression levels of VEGF, erythropoietin, angiopoietin 1 and 2, and NADPH oxidase were examined in rat retinas by RT-PCR and Western blot. Superoxide formation was examined by dihydroethidium (DHE) staining. RESULTS:DHE analysis revealed increased superoxide formation in the retinas of the diabetic group, which was decreased in the group treated with simvastatin. Western blot analysis showed that NADPH oxidase levels were decreased in the diabetic group and remained normal in the simvastatin-treated group. Simvastatin treatment blocked hyperglycemia-induced increases in VEGF, angiopoietin 2 and erythropoietin levels, as demonstrated by RT-PCR and Western blot analysis. CONCLUSIONS:Simvastatin treatment led to suppression of superoxide formation and decreased expression of VEGF, angiopoietin 2 and erythropoietin in diabeticrat retinas.
Authors: Mohamed Al-Shabrawey; Manuela Bartoli; Azza B El-Remessy; Daniel H Platt; Sue Matragoon; M Ali Behzadian; Robert W Caldwell; Ruth B Caldwell Journal: Am J Pathol Date: 2005-08 Impact factor: 4.307
Authors: Rania Harfouche; Nelly Abdel Malak; Ralf P Brandes; Aly Karsan; Kaikobad Irani; Sabah N A Hussain Journal: FASEB J Date: 2005-07-27 Impact factor: 5.191
Authors: Ruth B Caldwell; Manuela Bartoli; M Ali Behzadian; Azza E B El-Remessy; Mohamed Al-Shabrawey; Daniel H Platt; Gregory I Liou; R William Caldwell Journal: Curr Drug Targets Date: 2005-06 Impact factor: 3.465
Authors: Randa S Eshaq; Megan N Watts; Patsy R Carter; Wendy Leskova; Tak Yee Aw; Jonathan Steven Alexander; Norman R Harris Journal: Pathophysiology Date: 2021-03-02