Expression of neutrophil gelatinase‑associated lipocalin in low osmolar contrast‑induced nephropathy in rats and the effect of N‑acetylcysteine

Li,Wen‑Hua; Wang,Lin; He,Hai‑Yan; Chen,Jing; Yu,Ya‑Ren

doi:10.3892/etm.2016.3779

Expression of neutrophil gelatinase‑associated lipocalin in low osmolar contrast‑induced nephropathy in rats and the effect of N‑acetylcysteine

Authors:
- Wen‑Hua Li
- Lin Wang
- Hai‑Yan He
- Jing Chen
- Ya‑Ren Yu
View Affiliations

Affiliations: Department of Cardiology, Institute of Cardiovascular Diseases Research, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China
Published online on: October 4, 2016 https://doi.org/10.3892/etm.2016.3779
Pages: 3175-3180
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Serum creatinine (Scr), which is a conventional indicator of contrast‑induced nephropathy (CIN), is unable to reflect the damage of kidney promptly. The present study aimed to investigate the value of neutrophil gelatinase‑associated lipocalin (NGAL) in kidney and serum of CIN rats to observe whether NGAL can be used as a superior indicator of CIN. Furthermore, N‑acetylcysteine (NAC) was used to assess its effect on CIN. A total of 120 adult male Sprague Dawley rats were randomly divided into four groups (n=30/group): CIN rats (CIN), normal rats treated with NAC (NAC), CIN rats treated with NAC (NAC+CIN) and the control group (CON). Serum Scr and NGAL values were measured at 2, 12, 24, 48 and 72 h following the procedure. Immunohistochemistry and western blot analysis were used to detect NGAL within the kidney tissue. Hematoxylin and eosin staining were used to access the renal injury score. Oxidative stress within the kidney was analyzed via malondialdehyde (MDA) and superoxide dismutase (SOD). The level of NGAL in the serum and tissue of the CIN group increased significantly 2 h after the procedure (P<0.05). However, the Scr value did not exhibit a significantly change until 48 h later. Based on the renal injury scores, NAC reduced the kidney damage caused by the contrast. NAC treatment was associated with a decrease in SOD levels and an increase in MDA. These findings suggested that NGAL was a superior indicator of CIN than Scr, as NGAL was able to detect kidney damage much earlier. Furthermore, NAC treatment inhibited oxidative stress, thus protecting against CIN.

View Figures

View References

1	Nash K, Hafeez A and Hou S: Hospital-acquired renal insuffciency. Am J Kidney Dis. 39:930–936. 2002. View Article : Google Scholar : PubMed/NCBI
2	Bonventre JV, Vaidya VS, Schmouder R, Feig P and Dieterle F: Next-generation biomarkers for detecting kidney toxicity. Nature Biotechnol. 28:436–440. 2010. View Article : Google Scholar
3	Patsaoura A, Tatsi E, Margeli A, Kanavaki I, Delaporta P, Kyriakopoulou D, Kouraklis-Symeonidis A, Kattamis A and Papassotiriou I: Plasma neutrophil gelatinase-associated lipocalin levels are markedly increased in patients with non-transfusion-dependent thalassemia: Lack of association with markers of erythropoiesis, iron metabolism and renal function. Clin Biochem. 47:1060–1064. 2014. View Article : Google Scholar : PubMed/NCBI
4	Finn WF: The clinical and renal consequences of contrast-induced nephropathy. Nephrol Dial Transplant. 21:i2–i10. 2006. View Article : Google Scholar : PubMed/NCBI
5	Tepel M, Aspelin P and Lameire N: Contrast-induced nephropathy: A clinical and evidence-based approach. Circulation. 113:1799–1806. 2006. View Article : Google Scholar : PubMed/NCBI
6	Mehran R and Nikolsky E: Contrast-induced nephropathy: Definition, epidemiology, and patients at risk. Kidney Int Suppl. S11–S15. 2006. View Article : Google Scholar : PubMed/NCBI
7	Goldenberg I and Matetzky S: Nephropathy induced by contrast media: Pathogenesis, risk factors and preventive strategies. CMAJ. 172:1461–1471. 2005. View Article : Google Scholar : PubMed/NCBI
8	Briguori C, Tavano D and Colombo A: Contrast agent-associated nephrotoxicity. Prog Cardiovasc Dis. 45:493–503. 2003. View Article : Google Scholar : PubMed/NCBI
9	Toprak O and Cirit M: Risk factors for contrast-induced nephropathy. Kidney Blood Press Res. 29:84–93. 2006. View Article : Google Scholar : PubMed/NCBI
10	Katzberg RW: Urography into the 21st century: New contrast media, renal handling, imaging characteristics, and nephrotoxicity. Radiology. 204:297–312. 1997. View Article : Google Scholar : PubMed/NCBI
11	Tumlin J, Stacul F, Adam A, Becker CR, Davidson C, Lameire N and McCullough PA: CIN Consensus Working Panel: Pathophysiology of contrast-induced nephropathy. Am J Cardiol. 98:14K–20K. 2006. View Article : Google Scholar : PubMed/NCBI
12	Perrin T, Descombes E and Cook S: Contrast-induced nephropathy in invasive cardiology. Swiss Med Wkly. 142:w136082012.PubMed/NCBI
13	Yokomaku Y, Sugimoto T, Kume S, Araki S, Isshiki K, Chin-Kanasaki M, Sakaguchi M, Nitta N, Haneda M, Koya D, et al: Asialoerythropoietin prevents contrast-induced nephropathy. J Am Soc Nephrol. 19:321–328. 2008. View Article : Google Scholar : PubMed/NCBI
14	James MT, Ghali WA, Tonelli M, Faris P, Knudtson ML, Pannu N, Klarenbach SW, Manns BJ and Hemmelgarn BR: Acute kidney injury following coronary angiography is associated with a long-term decline in kidney function. Kidney Int. 78:803–809. 2010. View Article : Google Scholar : PubMed/NCBI
15	James MT, Ghali WA, Knudtson ML, Ravani P, Tonelli M, Faris P, Pannu N, Manns BJ, Klarenbach SW, Hemmelgarn BR, et al: Associations between acute kidney injury and cardiovascular and renal outcomes after coronary angiography. Circulation. 123:409–416. 2011. View Article : Google Scholar : PubMed/NCBI
16	Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2:1–138. 2012.
17	Bellomo R, Kellum JA and Ronco C: Defining acute renal failure: Physiological principles. Intensive Care Med. 30:33–37. 2004. View Article : Google Scholar : PubMed/NCBI
18	Cowland JB and Borregaard N: Molecular characterization and pattern of tissue expression of the gene for NGAL from humans. Genomics. 45:17–23. 1997. View Article : Google Scholar : PubMed/NCBI
19	Mishra J, Mor IK, Ma Q, Kelly C, Yang J, Mitsnefes M, Barasch J and Devarajan P: Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol. 15:3073–3082. 2004. View Article : Google Scholar : PubMed/NCBI
20	Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, Syed H, Ali S, Barasch J and Devarajan P: Urine NGAL predicts severity of acute kidney injury after cardiac surgery: A prospective study. Clin J Am Soc Nephrol. 3:665–673. 2008. View Article : Google Scholar : PubMed/NCBI
21	Navaneethan SD, Singh S, Appasamy S, Wing RE and Sehgal AR: Sodium bicarbonate therapy for prevention of contrast-induced nephropathy: A systematic review and meta-analysis. Am J Kidney Dis. 53:617–627. 2009. View Article : Google Scholar : PubMed/NCBI
22	Recio-Mayoral A, Chaparro M, Prado B, Cózar R, Méndez I, Banerjee D, Kaski JC, Cubero J and Cruz JM: The reno-protective effect of hydration with sodium bicarbonate plus N-acetylcysteine in patients undergoing emergency percutaneous coronary intervention: The RENO study. J Am Coll Cardiol. 49:1283–1288. 2007. View Article : Google Scholar : PubMed/NCBI
23	Reinecke H, Fobker M, Wellmann J, Becke B, Fleiter J, Heitmeyer C, Breithardt G, Hense HW and Schaefer RM: A randomized controlled trial comparing hydration therapy to additional hemodialysis or N-acetylcysteine for the prevention of contrast medium-induced nephropathy: The Dialysis-versus-Diuresis (DVD) Trial. Clin Res Cardiol. 96:130–139. 2007. View Article : Google Scholar : PubMed/NCBI
24	Toprak O, Cirit M, Tanrisev M, Yazici C, Canoz O, Sipahioglu M, Uzum A, Ersoy R and Sozmen EY: Preventive effect of nebivolol on contrast-induced nephropathy in rats. Nephrol Dial Transplant. 23:853–859. 2008. View Article : Google Scholar : PubMed/NCBI
25	Goodman A, Olszanecki R, Yang LM, Quan S, Li M, Omura S, Stec DE and Abraham NG: Heme oxygenase-1 protects against radiocontrast-induced acute kidney injury by regulating anti-apoptotic proteins. Kidney Int. 72:945–953. 2007. View Article : Google Scholar : PubMed/NCBI
26	Katholi RE, Woods WT Jr, Taylor GJ, Deitrick CL, Womack KA, Katholi CR and McCann WP: Oxygen free radicals and contrast nephropathy. Am J Kidney Dis. 32:64–671. 1998. View Article : Google Scholar : PubMed/NCBI
27	Heyman SN, Rosen S, Khamaisi M, Idée JM and Rosenberger C: Reactive oxygen species and the pathogenesis of radiocontrast-induced nephropathy. Invest Radiol. 45:188–195. 2010. View Article : Google Scholar : PubMed/NCBI