Sodium-glucose cotransporter inhibition prevents oxidative stress in the kidney of diabetic rats.

Abstract

UNLABELLED:

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.

• Authors: Horacio Osorio, Israel Coronel, Abraham Arellano, Ursino Pacheco, Rocío Bautista, Martha Franco, Bruno Escalante
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2012 Pg. 542042 ( 2012) ISSN: 1942-0994 [Electronic] United States
• PMID: 23227274 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Slc5a2 protein, rat
• Sodium-Glucose Transporter 2
• Sodium-Glucose Transporter 2 Inhibitors
• 3-nitrotyrosine
• Tyrosine
• Phlorhizin
• Catalase
• Glutathione Peroxidase
• Superoxide Dismutase

Topics

• Animals
• Catalase (metabolism)
• Diabetes Mellitus, Experimental (pathology, prevention & control)
• Glutathione Peroxidase (metabolism)
• Immunohistochemistry
• Kidney (drug effects, enzymology, pathology)
• Male
• Oxidative Stress (drug effects)
• Phlorhizin (pharmacology)
• Rats
• Rats, Wistar
• Sodium-Glucose Transporter 2 (metabolism)
• Sodium-Glucose Transporter 2 Inhibitors
• Superoxide Dismutase (metabolism)
• Tyrosine (analogs & derivatives, metabolism)