ABSTRACT
UNLABELLED: 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-ß-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. CONCLUSION: The tubular dysfunction evidenced by urinary excretion of NGAL precedes oxidative stress during diabetes.
Subject(s)
Acute-Phase Proteins/urine , Diabetes Mellitus, Experimental/urine , Diabetic Nephropathies/urine , Lipocalins/urine , Proto-Oncogene Proteins/urine , Animals , Biomarkers/urine , Diabetes Mellitus, Experimental/pathology , Diabetic Nephropathies/pathology , Lipocalin-2 , Male , Oxidative Stress/physiology , Rats , Rats, Wistar , Reactive Oxygen Species/metabolismABSTRACT
La persistencia de la hipertensión renovascular después de extirpar el riñón estenótico se atribuye a alteraciones del riñon contralateral (RC). Para identificar posibles mecanismos pertubadores de hipertensión se estudió la función de nefronas individuales en RC. Sesenta días después de aplicar el clip en arteria renal se extirpó el riñon estenótico en ratas y 120 días después se estudiaron con micropunción. Se midió filtración glomerular por nefroma (Fg), presión glomerular, permeabilidad glomerular (Kf), resistencia aferente (RA) y la respuesta de Fg a cambios de flujo tubular distal (FTD). La HTA se asoció a la elvación de RA, la filtración no varó a pesar de la maypor presión glomerular (PG), indicando disminución de permeabilidad glomerular. Esto disminuyó la respuesta de Fg al FTD. Estos cambios son capaces de generar hipertensión o contribuir a perpetuarla; pueden ser producidos por cambios estructurales en el capilar glomerular o por generación local de angiotensina
