Abstract
The hyperglycemia triggers several chronic diabetic complications mediated by increased oxidative stress that eventually causes diabetic nephropathy. The aim of this study was to examine if the sodium-glucose cotransporter (SGLT2) inhibition prevents the oxidative stress in the kidney of diabetic rats. Methods. The diabetic rat model was established by intraperitoneal injection of streptozotocin (50 mg/kg). The inhibition of SGLT2 was induced by daily subcutaneous administration of phlorizin (0.4 g/kg). Oxidative stress was assessed by catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities and by immunohistochemical analysis of 3-nitrotyrosine (3-NT). Results. Streptozotocin-induced diabetes caused hyperglycemia and lower body weight. The CAT activity decreased in cortex and medulla from diabetic rats; in contrast, the GPx activity increased. Furthermore the 3-NT staining of kidney from diabetic rats increased compared to control rats. The inhibition of SGLT2 decreased hyperglycemia. However, significant diuresis and glucosuria remain in diabetic rats. The phlorizin treatment restores the CAT and GPX activities and decreases 3-NT staining. Conclusion. The inhibition of SGLT2 by phlorizin prevents the hyperglycemia and oxidative stress in kidney of diabetic rats, suggesting a prooxidative mechanism related to SGLT2 activity.
Highlights
Diabetic nephropathy (DN) is a leading cause of end-stage renal failure, accounting for 35% to 40% of all new cases that require dialysis therapy worldwide
Animals were randomly divided into four groups: control (C), diabetic (D), diabetic treated with phlorizin (DP), and diabetic treated with insulin (DI)
Diabetes induction was followed by significant increases in renal oxidative stress evidenced by low CAT activity, whereas glutathione peroxidase (GPx) was increased; diabetic rats showed increase in nitrotyrosine levels in cortex and medulla
Summary
Diabetic nephropathy (DN) is a leading cause of end-stage renal failure, accounting for 35% to 40% of all new cases that require dialysis therapy worldwide. Several evidences suggest that the controlling of glucose in the renal proximal tubular could play a major role in the genesis of diabetic systemic complications [2, 3]. We have reported increased sodium glucose cotransporter (SGLT2) activity and expression in rats with diabetes and salt sensitivity [6, 7]. We showed that the increase in oxidative stress and SGLT2 expression was prevented by ursodeoxycholic acid treatment in diabetic rats [8]
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