title: Sodium-glucose cotransporter inhibition prevents oxidative stress in the kidney of diabetic rats.
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.
  
  
  CONCLUSIONS
  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.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, 14080 Mexico City, DF, Mexico. horace_33@yahoo.com.mx
authors.forename: Horacio
authors.initials: H
authors.lastname: Osorio
authors.forename: Israel
authors.initials: I
authors.lastname: Coronel
authors.forename: Abraham
authors.initials: A
authors.lastname: Arellano
authors.forename: Ursino
authors.initials: U
authors.lastname: Pacheco
authors.forename: Rocío
authors.initials: R
authors.lastname: Bautista
authors.forename: Martha
authors.initials: M
authors.lastname: Franco
authors.forename: Bruno
authors.initials: B
authors.lastname: Escalante
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology* / Q000517:prevention & control*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C490300:Slc5a2 protein, rat; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C002744:3-nitrotyrosine; D014443:Tyrosine; D010695:Phlorhizin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase