Urinary excretion of neutrophil gelatinase-associated lipocalin in diabetic rats.

Abraham Said Arellano-Buendía,Magdalena Cristóbal-García,Horacio Osorio-Alonso,Edilia Tapia-Rodríguez,María Lilia Loredo-Mendoza,Laura Gabriela Sánchez-Lozada,Fernando Enrique García-Arroyo

doi:10.1155/2014/961326

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. Conclusion. The tubular dysfunction evidenced by urinary excretion of NGAL precedes oxidative stress during diabetes.

Highlights

Diabetic nephropathy (DN) is the primary cause of end stage renal disease (ESRD), described as a worldwide medical catastrophe
There were no significant differences between experimental groups in proteinuria, albuminuria, serum creatinine, urinary creatinine, or creatinine clearance
Diabetic nephropathy has traditionally been considered as a glomerular disease; it is widely accepted that the rate of deterioration in renal function correlates best with the degree of tubulointerstitial damage [19]

Summary

Introduction

Diabetic nephropathy (DN) is the primary cause of end stage renal disease (ESRD), described as a worldwide medical catastrophe. Persistent hyperglycemia through glucose autoxidation and defective antioxidant defenses causes increased production of reactive oxygen species (ROS) [3, 4]. This excessive ROS production and subsequent oxidative damage have been suggested as common outcomes of diabetes, which culminates in DN [4]. The impairment of renal function in DN patients has long been diagnosed using biochemistry tools, including measurement of serum creatinine (SCr) and blood urea nitrogen (BUN). These are not reliable markers of early loss of renal function, delaying therapeutic interventions in order to stop or slow progression of renal damage. Microalbuminuria has recently emerged as a sensitive marker of early renal damage; this measurement lacks the sensitivity to detect the earliest changes in renal function

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