N-acetylcysteine ameliorates contrast‑induced kidney injury in rats with unilateral hydronephrosis

Xia,Qiang; Liu,Chunxiao; Zheng,Xia

doi:10.3892/mmr.2017.8122

N-acetylcysteine ameliorates contrast‑induced kidney injury in rats with unilateral hydronephrosis

Authors:
- Qiang Xia
- Chunxiao Liu
- Xia Zheng
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Affiliations: Department of Urology, Wuxi Ninth People's Hospital, Wuxi, Jiangsu 214062, P.R. China, Department of Urology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510280, P.R. China, Department of Comparative Medicine, Guangdong Medical Laboratory Animal Center, Foshan, Guangdong 528248, P.R. China
Published online on: November 21, 2017 https://doi.org/10.3892/mmr.2017.8122
Pages: 2203-2210
Copyright: © Xia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the protective effects of N‑acetylcysteine (NAC) on contrast‑induced acute kidney injury in rats with unilateral hyronephrosis. Eighty‑two male Sprague Dawley rats were randomized to undergo sham operation (n=14) or unilateral ureteral obstruction (UUO) (n=68). After 3 weeks, the UUO animals were randomized to three groups: NAC gastric perfusion, UUO+iohexol+NAC (n=24); normal saline perfusion, UUO+iohexol (n=24); and controls, UUO (n=20). After 3 days, UUO+iohexol+NAC and UUO+iohexol rats were injected with iohexol. One day after contrast, half of the rats were sacrificed to assess the pathological changes to the kidneys, serum creatinine, serum neutrophil gelatinase‑associated lipocalin (NGAL), renal cell apoptosis rate and expression of apoptosis regulators Bcl‑2/Bax. The remaining rats underwent obstruction relief and were analyzed 3 weeks later. Compared with the controls, serum NGAL levels were high in UUO+iohexol rats 1 day following injection and 3 weeks after obstruction relief, but UUO+iohexol+NAC rats exhibited lower serum NGAL levels compared with UUO+iohexol rats (all P<0.05). Following modeling, UUO+iohexol rats exhibited a significantly higher apoptosis rate of renal tubular cells, higher expression of Bax mRNA, and lower ratio of Bcl‑2/Bax (all P<0.05). Three weeks after obstruction relief, UUO+iohexol+NAC rats exhibited a lower apoptosis rate, lower Bax mRNA expression, higher expression of Bcl‑2 mRNA and higher ratio of Bcl‑2/Bax (all P<0.05) compared with day 1 following drug administration. The prophylactic use of NAC reduced the apoptotic rate of renal tubular cells following contrast exposition, which was accompanied by changes in the expression of Bcl‑2/Bax mRNA.

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1	Kumar V, Fausto N and Abbas AK: Robbins and Cotran Pathologic Basis of Disease. 7th. Elsevier Saunders; Philadelphia: 2005
2	Chevalier RL: Pathophysiology of obstructive nephropathy in the newborn. Semin Nephrol. 18:585–593. 1998.PubMed/NCBI
3	Rudnick MR, Goldfarb S and Tumlin J: Contrast-induced nephropathy: Is the picture any clearer? Clin J Am Soc Nephrol. 3:261–262. 2008. View Article : Google Scholar : PubMed/NCBI
4	Berg KJ: Nephrotoxicity related to contrast media. Scand J Urol Nephrol. 34:317–322. 2000. View Article : Google Scholar : PubMed/NCBI
5	Pattharanitima P and Tasanarong A: Pharmacological strategies to prevent contrast-induced acute kidney injury. Biomed Res Int. 2014:2369302014. View Article : Google Scholar : PubMed/NCBI
6	Gurm HS, Smith DE, Berwanger O, Share D, Schreiber T, Moscucci M and Nallamothu BK; BMC2 (Blue Cross Blue Shield of Michigan Cardiovascular Consortium), : Contemporary use and effectiveness of N-acetylcysteine in preventing contrast-induced nephropathy among patients undergoing percutaneous coronary intervention. JACC Cardiovasc Interv. 5:98–104. 2012. View Article : Google Scholar : PubMed/NCBI
7	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
8	Persson PB, Hansell P and Liss P: Pathophysiology of contrast medium-induced nephropathy. Kidney Int. 68:14–22. 2005. View Article : Google Scholar : PubMed/NCBI
9	Brezis M and Rosen S: Hypoxia of the renal medulla-its implications for disease. N Engl J Med. 332:647–655. 1995. View Article : Google Scholar : PubMed/NCBI
10	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
11	Romano G, Briguori C, Quintavalle C, Zanca C, Rivera NV, Colombo A and Condorelli G: Contrast agents and renal cell apoptosis. Eur Heart J. 29:2569–2576. 2008. View Article : Google Scholar : PubMed/NCBI
12	Kelly AM, Dwamena B, Cronin P, Bernstein SJ and Carlos RC: Meta-analysis: Effectiveness of drugs for preventing contrast-induced nephropathy. Ann Intern Med. 148:284–294. 2008. View Article : Google Scholar : PubMed/NCBI
13	Sunay M, Karakan T, Aydin A, Koca G, Borcek P and Öğüş E: Do montelukast sodium and N-acetylcysteine have a nephroprotective effect on unilateral ureteral obstruction? A placebo controlled trial in a rat model. J Urol. 194:1132–1137. 2015. View Article : Google Scholar : PubMed/NCBI
14	Inda-Filho AJ, Caixeta A, Manggini M and Schor N: Do intravenous N-acetylcysteine and sodium bicarbonate prevent high osmolal contrast-induced acute kidney injury? A randomized controlled trial. PLoS One. 9:e1076022014. View Article : Google Scholar : PubMed/NCBI
15	Rehman T, Fought J and Solomon R: N-acetylcysteine effect on serum creatinine and cystatin C levels in CKD patients. Clin J Am Soc Nephrol. 3:1610–1614. 2008. View Article : Google Scholar : PubMed/NCBI
16	Chaabane W, Praddaude F, Buleon M, Jaafar A, Vallet M, Rischmann P, Galarreta CI, Chevalier RL and Tack I: Renal functional decline and glomerulotubular injury are arrested but not restored by release of unilateral ureteral obstruction (UUO). Am J Physiol Renal Physiol. 304:F432–F439. 2013. View Article : Google Scholar : PubMed/NCBI
17	Efrati S, Berman S, Ilgiyeav I, Siman-Tov Y, Averbukh Z and Weissgarten J: Differential effects of N-acetylcysteine, theophylline or bicarbonate on contrast-induced rat renal vasoconstriction. Am J Nephrol. 29:181–191. 2009. View Article : Google Scholar : PubMed/NCBI
18	Shen Y, Miao NJ, Xu JL, Gan XX, Xu D, Zhou L, Xue H, Zhang W and Lu LM: N-acetylcysteine alleviates angiotensin II-mediated renal fibrosis in mouse obstructed kidneys. Acta Pharmacol Sin. 37:637–644. 2016. View Article : Google Scholar : PubMed/NCBI
19	Liapis H, Yu H and Steinhardt GF: Cell proliferation, apoptosis, Bcl-2 and Bax expression in obstructed opossum early metanephroi. J Urol. 164:511–517. 2000. View Article : Google Scholar : PubMed/NCBI
20	Skott M, Nørregaard R, Sorensen HB, Kwon TH, Frøkiaer J and Nielsen S: Pre-existing renal failure worsens the outcome after intestinal ischaemia and reperfusion in rats. Nephrol Dial Transplant. 25:3509–3517. 2010. View Article : Google Scholar : PubMed/NCBI
21	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
22	Devrim E, Cetin M, Namuslu M, Ergüder IB, Cetin R and Durak I: Oxidant stress due to non ionic low osmolar contrast medium in rat kidney. Indian J Med Res. 130:433–436. 2009.PubMed/NCBI
23	Nicholson T and Downes M: Contrast nephrotoxicity and iso-osmolar contrast agents: Implications of NEPHRIC. Clin Radiol. 58:659–660. 2003. View Article : Google Scholar : PubMed/NCBI
24	Yeh CH, Chiang HS, Lai TY and Chien CT: Unilateral ureteral obstruction evokes renal tubular apoptosis via the enhanced oxidative stress and endoplasmic reticulum stress in the rat. Neurourol Urodyn. 30:472–479. 2011. View Article : Google Scholar : PubMed/NCBI
25	Weisbord SD and Palevsky PM: Prevention of contrast-induced nephropathy with volume expansion. Clin J Am Soc Nephrol. 3:273–280. 2008. View Article : Google Scholar : PubMed/NCBI
26	Baliga R, Ueda N, Walker PD and Shah SV: Oxidant mechanisms in toxic acute renal failure. Am J Kidney Dis. 29:465–477. 1997. View Article : Google Scholar : PubMed/NCBI
27	Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D and Zidek W: Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 343:180–184. 2000. View Article : Google Scholar : PubMed/NCBI
28	Shyu KG, Cheng JJ and Kuan P: Acetylcysteine protects against acute renal damage in patients with abnormal renal function undergoing a coronary procedure. J Am Coll Cardiol. 40:1383–1388. 2002. View Article : Google Scholar : PubMed/NCBI
29	Kay J, Chow WH, Chan TM, Lo SK, Kwok OH, Yip A, Fan K, Lee CH and Lam WF: Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: A randomized controlled trial. JAMA. 289:553–558. 2003. View Article : Google Scholar : PubMed/NCBI
30	Li H, Chen J, Xiong C, Wei H, Yin C and Ruan J: Apoptosis induction by the total flavonoids from arachniodes exilis in HepG2 cells through reactive oxygen species-mediated mitochondrial dysfunction involving MAPK activation. Evid Based Complement Alternat Med. 2014:9069412014. View Article : Google Scholar : PubMed/NCBI
31	Yuan Y, Wang Y, Hu FF, Jiang CY, Zhang YJ, Yang JL, Zhao SW, Gu JH, Liu XZ, Bian JC and Liu ZP: Cadmium activates reactive oxygen species-dependent AKT/mTOR and mitochondrial apoptotic pathways in neuronal cells. Biomed Environ Sci. 29:117–126. 2016.PubMed/NCBI
32	Gao H, Li LY, Zhang M and Zhang Q: Inactivated Sendai virus induces apoptosis mediated by reactive oxygen species in murine melanoma cells. Biomed Environ Sci. 29:877–884. 2016.PubMed/NCBI
33	Jiang H, Zhao PJ, Su D, Feng J and Ma SL: Paris saponin I induces apoptosis via increasing the Bax/Bcl-2 ratio and caspase-3 expression in gefitinib-resistant non-small cell lung cancer in vitro and in vivo. Mol Med Rep. 9:2265–2272. 2014.PubMed/NCBI