RESEARCH ARTICLE


The Effectiveness of N-acetylcysteine in Alleviating Kidney Dysfunction in Ifosfamide-treated Rats



Lukasz Dobrek1, *, Klaudia Nalik-Iwaniak2, Zbigniew Arent2
1 Department of Clinical Pharmacology, Wroclaw Medical University, Wroclaw, Poland
2 Experimental and Innovative Medicine Centre, University Centre of Veterinary Medicine, University of Agriculture, Krakow, Poland


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Creative Commons License
© 2020 Dobrek et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at Department of Clinical Pharmacology Wroclaw Medical University Borowska Str. 211A, 50-556 Wroclaw, Poland; Tel: 00 48 71 7840595; Fax: 00 48 71 7840602; E-mail: xlukaszx@onet.eu


Abstract

Background:

Renal damage and dysfunction are possible complications of pharmacotherapy with ifosfamide (IF), which also manifests urotoxic properties. A routine drug used to reduce the risk of IF-induced cystitis is mesna. Compounds with effect expected to be similar to mesna include N-acetylcysteine (NAC).

Objective:

The objective of the paper was histopathological verification of the uroprotective effect of NAC and assessment of whether this effect is accompanied by a potential nephroprotective effect.

Methods:

The experiment was conducted on 3 groups: 1 – control, sham-treated rats, 2 – animals treated with 5 times the IF dose administered i.p. (50 mg/kg b.w.) and 3 – rats treated with 5 times the IF dose administered i.p. + NAC administered p.o. (200 mg/kg b.w.). The renal function was evaluated analysing classical and new protein parameters (cystatin C - CysC, kidney injury molecule-1 – KIM-1 and nephrin - NPH) in blood and urine. Furthermore, histopathological analysis of bladders and kidneys was carried out.

Results:

Treatment with IF resulted in the development of cystitis, with no significant histopathological disturbances in the kidneys, and caused an increase in concentration and 24-hour excretion of CysC, KIM-1 NPH in the urine. Additional NAC administration caused a reduction of the said biochemical disturbances as well as improvement of the histopathological image of the urinary bladders.

Conclusion:

The IF therapy caused cystitis and kidney dysfunction of functional tubulopathy and early glomerulopathy character. Additional administration of NAC entailed improvement in the urinary bladder morphology and renal function. NAC is, thus, a compound exerting both uro- and nephroprotective effects.

Keywords: Cystatin c, Ifosfamide, N-acetylcysteine, Nephrin, Kidney Injury molecule-1, Rats.