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Intensive Care Medicine
Published in: Intensive Care Medicine 1/2011

01-01-2011 | Experimental

Could nephrotoxicity due to colistin be ameliorated with the use of N-acetylcysteine?

Authors: Ezgi Ozyilmaz, Fatma Ayerden Ebinc, Ulver Derici, Ozlem Gulbahar, Guleser Goktas, Cigdem Elmas, I. Kivilcim Oguzulgen, Sukru Sindel

Published in: Intensive Care Medicine | Issue 1/2011

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Abstract

Purpose

The protective effect of N-acetylcysteine (NAC) on nephrotoxicity due to contrast nephropathy and reperfusion-induced ischemia has been reported in experimental models. However, its efficacy on colistin-induced nephrotoxicity has not been elucidated yet. The primary aim of this study was to evaluate the nephrotoxic effect of colistin and to investigate the possible protective effect of NAC on colistin-induced nephrotoxicity. The secondary aim was to research the systemic effects of nephrotoxicity-induced oxidative stress on the lung.

Methods

Eighteen female Sprague-Dawley rats were randomly assigned and were given (a) 1 ml/kg sterile saline, (b) 300,000 IU/kg/day colistin, and (c) 300,000 IU/kg/day colistin and 150 mg/kg NAC for six consecutive days.

Results

Plasma blood urea nitrogen (BUN), creatinine, urinary creatinine, urinary protein, plasma TNF-alpha levels, renal tissue superoxide dismutase (SOD) and malondialdehyde (MDA) activity and immunocytochemical findings were evaluated. Colistin exerted nephrotoxicity and achieved a significant increase in plasma BUN and creatinine levels and renal tissue SOD levels. NAC exhibited no significant effect on biochemical parameters but reduced renal tissue SOD level and reversed immunocytochemical staining of inducible nitric oxide synthase (i-NOS) and neurotrophin-3. Increased oxidative stress in the lung tissue of the rats treated with colistin has also been documented. Additionally, NAC significantly reduced the immunostaining of endothelial NOS (e-NOS) and i-NOS in the lung tissue.

Conclusions

Colistin-induced renal toxicity may be attributable to oxidative damage. The combined treatment of colistin plus NAC seems to have a beneficial role in restoration of the oxidant injury which may be related to its antioxidant effect.
Appendix
Available only for authorised users
Literature
1.
Michalopoulos AS, Falagas ME (2008) Colistin and polymyxin B in critical care. Crit Care Clin 24:377–391CrossRefPubMed
2.
Michalopoulos AS, Tsiodras S, Rellos K, Menzelopoulos S, Falagas ME (2005) Colistin treatment in patients with ICU-acquired infections caused by multidrug resistant gram negative bacteria: the renaissance of an old antibiotic. Clin Microbiol Infect 11:115–121CrossRefPubMed
3.
Zavacki AP, Goldani LZ, Li J, Nation RL (2007) Polymyxin B for the treatment of multidrug resistant pathogens: a critical review. J Antimicrob Chemother 60:1206–1215CrossRef
4.
Falagas ME, Kasiakou SK (2005) Colistin: the revival of polymyxins for the management of multidrug resistant gram negative bacterial infections. Clin Infect Dis 40:1333–1341CrossRefPubMed
5.
Aitio ML (2005) N-acetylcysteine—passé-partout or much ado about nothing? Br J Clin Pharmacol 61:5–15CrossRef
6.
Petronilho F, Constantino L, de Souza B, Reinke A, Martins MR, Fraga CM, Ritter C, Dal-Pizzol F (2009) Efficacy of the combination of N-acetylcysteine and desferrioxamine in the prevention and treatment of gentamicin-induced acute renal failure in male Wistar rats. Nephrol Dial Transplant 24:2077–2082CrossRefPubMed
7.
Bagshaw SM, McAlister FA, Manns BJ, Ghali WA (2006) Acetylcysteine in the prevention of contrast induced nephropathy: a case study of the pitfalls in the evaluation of evidence. Arch Intern Med 166:161–166CrossRefPubMed
8.
McCarty KS Jr, Miller RS (1985) Estrogen receptor analysis. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med 109:716–721PubMed
9.
Markou N, Apostolakos H, Koumoudiou C, Athanasiou M, Koutsoukou A, Alamanos I, Gregorakos L (2003) Intravenous colistin in the treatment of sepsis from multidrug resistant gram negative bacilli in critically ill patients. Crit Care 7:R78–R83CrossRefPubMed
10.
Falagas ME, Kasiakou SK (2006) Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Crit Care 10:R27CrossRefPubMed
11.
Reed MD, Stern RC, O’Riordan MA, Blumer JL (2001) The pharmacokinetics of colistin in patients with cystic fibrosis. J Clin Pharmacol 41:645–654CrossRefPubMed
12.
Falagas ME, Rizos M, Bliziotis IA, Rellos K, Kasiakou SK, Michalopoulos A (2005) Toxicity after prolonged (more than four weeks) administration of intravenous colistin. BMC Infect Dis 5:1CrossRefPubMed
13.
Dekhuijzen PNR (2004) Antioxidant properties of N-acetylcysteine: their relevance in relation to chronic obstructive pulmonary disease. Eur Respir J 23:629–636CrossRefPubMed
14.
Senoglu N, Yuzbasioglu MF, Aral M, Ezberci M, Kurutas EB, Bulbuloglu E, Ezberci F, Oksuz H, Ciragil P (2008) Protective effects of N-acetylcysteine and beta-glucan pretreatment on oxidative stress in cecal ligation and puncture model of sepsis. J Invest Surg 21:237–243CrossRefPubMed
15.
Erturk E, Cekic B, Geze S, Kosucu M, Coskun I, Eroglu A, Ulusoy H, Mentese A, Karahan C, Kerimoglu S (2009) Comparison of the effect of propofol and N-acetyl cysteine in preventing ischaemia-reperfusion injury. Eur J Anaesthesiol 26:279–284CrossRefPubMed
16.
Ali BH, Al Salam S, Al-Husseini I, Nemmar A (2009) Comparative protective effect of N-acetyl cysteine and tetramethylpyrazine in rats with gentamicin nephrotoxicity. J Appl Toxicol 29:302–308CrossRefPubMed
17.
Luo J, Tsuji T, Yasuda H, Sun Y, Fujigaki Y, Hishida A (2008) The molecular mechanisms of the attenuation of cisplatin-induced acute renal failure by N-acetylcysteine in rats. Nephrol Dial Transplant 23:2198–2205CrossRefPubMed
18.
Ghaznavi R, Kadkhodaee M (2007) Comparative effects of selective and non-selective nitric oxide synthase inhibition in gentamicin-induced rat nephrotoxicity. Arch Toxicol 81:453–457CrossRefPubMed
Metadata
Title
Could nephrotoxicity due to colistin be ameliorated with the use of N-acetylcysteine?
Authors
Ezgi Ozyilmaz
Fatma Ayerden Ebinc
Ulver Derici
Ozlem Gulbahar
Guleser Goktas
Cigdem Elmas
I. Kivilcim Oguzulgen
Sukru Sindel
Publication date
01-01-2011
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 1/2011
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-010-2038-7

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