title: Urinary excretion of neutrophil gelatinase-associated lipocalin in diabetic rats.
abstract: Recent studies suggest that tubular damage precedes glomerular damage in the progression of diabetic nephropathy. Therefore, we evaluated oxidative stress and urinary excretion of tubular proteins as markers of tubular dysfunction.
  
  
  METHODS
  Diabetes was induced in rats by streptozotocin administration (50 mg/kg). Oxidative stress was assessed by measuring the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD); additionally, expression levels of 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), and oxidized protein (OP) were quantified. Whole glomerular filtration rate (GFR) was measured. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin (uOPN), and N-acetyl-β-D-glucosaminidase (uNAG) was also determined.
  
  
  RESULTS
  Diabetic rats showed an increase in uNGAL excretion 7 days following induction of diabetes. Diuresis, proteinuria, albuminuria, creatinine clearance, and GFR were significantly increased by 30 days after induction. Furthermore, there was an increase in both CAT and SOD activity, in addition to 3-NT, 4-HNE, and OP expression levels. However, GPx activity was lower. Serum levels of NGAL and OPN, as well as excretion levels of uNGAL, uOPN, and uNAG, were increased in diabetics. Tubular damage was observed by 7 days after diabetes induction and was further aggravated by 30 days after induction.
  
  
  CONCLUSIONS
  The tubular dysfunction evidenced by urinary excretion of NGAL precedes oxidative stress during diabetes.
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, 14080 México City, DF, Mexico.
authors.forename: Abraham Said
authors.initials: AS
authors.lastname: Arellano-Buendía
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, 14080 México City, DF, Mexico.
authors.forename: Fernando Enrique
authors.initials: FE
authors.lastname: García-Arroyo
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, 14080 México City, DF, Mexico.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cristóbal-García
authors.affiliation: Histopathology Laboratory, Research Subdivision, School of Medicine, Universidad Panamericana, Donatello 43, 03910 México City, DF, Mexico.
authors.forename: María Lilia
authors.initials: ML
authors.lastname: Loredo-Mendoza
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, 14080 México City, DF, Mexico.
authors.forename: Edilia
authors.initials: E
authors.lastname: Tapia-Rodríguez
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, 14080 México City, DF, Mexico.
authors.forename: Laura Gabriela
authors.initials: LG
authors.lastname: Sánchez-Lozada
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, 14080 México City, DF, Mexico.
authors.forename: Horacio
authors.initials: H
authors.lastname: Osorio-Alonso
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine*; D000818:Animals; D015415:Biomarkers / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000652:urine*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000652:urine*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species