Urinary Excretion of Neutrophil Gelatinase-associated Lipocalin in Diabetic Rats

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2014 Sep 23

PMID 25243053

Citations 11

Authors

Abraham Said Arellano-Buendia

Fernando Enrique Garcia-Arroyo

Magdalena Cristobal-Garcia

Maria Lilia Loredo-Mendoza

Edilia Tapia-Rodriguez

Laura Gabriela Sanchez-Lozada

Horacio Osorio-Alonso

Affiliations

Soon will be listed here.

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-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.

Citing Articles

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References

Bangstad H, Osterby R, Dahl-Jorgensen K, Berg K, Hartmann A, Hanssen K . Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy. Diabetologia. 1994; 37(5):483-90. DOI: 10.1007/s001250050136. View

Lorenzen J, Shah R, Biser A, Staicu S, Niranjan T, Garcia A . The role of osteopontin in the development of albuminuria. J Am Soc Nephrol. 2008; 19(5):884-90. PMC: 2386721. DOI: 10.1681/ASN.2007040486. View

Assal H, Tawfeek S, Rasheed E, El-Lebedy D, Thabet E . Serum cystatin C and tubular urinary enzymes as biomarkers of renal dysfunction in type 2 diabetes mellitus. Clin Med Insights Endocrinol Diabetes. 2013; 6:7-13. PMC: 3738377. DOI: 10.4137/CMED.S12633. View

Bohle A, Wehrmann M, Bogenschutz O, Batz C, Muller C, Muller G . The pathogenesis of chronic renal failure in diabetic nephropathy. Investigation of 488 cases of diabetic glomerulosclerosis. Pathol Res Pract. 1991; 187(2-3):251-9. DOI: 10.1016/s0344-0338(11)80780-6. View

Osorio H, Coronel I, Arellano A, Pacheco U, Bautista R, Franco M . Sodium-glucose cotransporter inhibition prevents oxidative stress in the kidney of diabetic rats. Oxid Med Cell Longev. 2012; 2012:542042. PMC: 3512343. DOI: 10.1155/2012/542042. View

Mishra J, Dent C, Tarabishi R, Mitsnefes M, Ma Q, Kelly C . Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005; 365(9466):1231-8. DOI: 10.1016/S0140-6736(05)74811-X. View

Rouse R, Stewart S, Thompson K, Zhang J . Kidney injury biomarkers in hypertensive, diabetic, and nephropathy rat models treated with contrast media. Toxicol Pathol. 2012; 41(4):662-80. DOI: 10.1177/0192623312464122. View

Osorio H, Bautista R, Rios A, Franco M, Santamaria J, Escalante B . Effect of treatment with losartan on salt sensitivity and SGLT2 expression in hypertensive diabetic rats. Diabetes Res Clin Pract. 2009; 86(3):e46-9. DOI: 10.1016/j.diabres.2009.09.006. View

Erdelmeier I, Yadan J, Chaudiere J . Reactions of N-methyl-2-phenylindole with malondialdehyde and 4-hydroxyalkenals. Mechanistic aspects of the colorimetric assay of lipid peroxidation. Chem Res Toxicol. 1998; 11(10):1184-94. DOI: 10.1021/tx970180z. View

10.

Mohammadi-Karakani A, Asgharzadeh-Haghighi S, Ghazi-Khansari M, Hosseini R . Determination of urinary enzymes as a marker of early renal damage in diabetic patients. J Clin Lab Anal. 2007; 21(6):413-7. PMC: 6649252. DOI: 10.1002/jcla.20212. View

11.

von Eynatten M, Baumann M, Heemann U, Zdunek D, Hess G, Nawroth P . Urinary L-FABP and anaemia: distinct roles of urinary markers in type 2 diabetes. Eur J Clin Invest. 2009; 40(2):95-102. DOI: 10.1111/j.1365-2362.2009.02220.x. View

12.

Mitsnefes M, Kathman T, Mishra J, Kartal J, Khoury P, Nickolas T . Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in children with chronic kidney disease. Pediatr Nephrol. 2006; 22(1):101-8. DOI: 10.1007/s00467-006-0244-x. View

13.

Fischer J, Tschope C, Reinecke A, Giachelli C, Unger T . Upregulation of osteopontin expression in renal cortex of streptozotocin-induced diabetic rats is mediated by bradykinin. Diabetes. 1998; 47(9):1512-8. DOI: 10.2337/diabetes.47.9.1512. View

14.

Uslu S, Efe B, Alatas O, Kebapci N, Colak O, Demirustu C . Serum cystatin C and urinary enzymes as screening markers of renal dysfunction in diabetic patients. J Nephrol. 2005; 18(5):559-67. View

15.

Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P . Neutrophil gelatinase-associated lipocalin: a novel early urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol. 2004; 24(3):307-15. DOI: 10.1159/000078452. View

16.

Wellwood J, Price R, Ellis B, THOMPSON A . A note on the practical aspects of the assay of N-acetyl-beta-glucosaminidase in human urine. Clin Chim Acta. 1976; 69(1):85-91. DOI: 10.1016/0009-8981(76)90475-7. View

17.

Levine R, Garland D, Oliver C, Amici A, Climent I, Lenz A . Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 1990; 186:464-78. DOI: 10.1016/0076-6879(90)86141-h. View

18.

Damman K, Van Veldhuisen D, Navis G, Vaidya V, Smilde T, Westenbrink B . Tubular damage in chronic systolic heart failure is associated with reduced survival independent of glomerular filtration rate. Heart. 2010; 96(16):1297-302. PMC: 3480323. DOI: 10.1136/hrt.2010.194878. View

19.

Skrha J, Perusicova J, Stolba P, Stibor V, Pav J . Comparison of N-acetyl-beta-glucosaminidase and albuminuria with clinical finding of microangiopathy in type I diabetes mellitus. Clin Chim Acta. 1987; 166(2-3):135-41. DOI: 10.1016/0009-8981(87)90415-3. View

20.

Fu W, Xiong S, Fang Y, Wen S, Chen M, Deng R . Urinary tubular biomarkers in short-term type 2 diabetes mellitus patients: a cross-sectional study. Endocrine. 2011; 41(1):82-8. DOI: 10.1007/s12020-011-9509-7. View