Osteopontin and fatty acid binding protein (FABP), as biomarkers of cyclophosphamide nephrotoxicity, in an experimental model of cystitis in rats

ORIGINAL ARTICLE

Osteopontin and fatty acid binding protein (FABP), as biomarkers of cyclophosphamide nephrotoxicity, in an experimental model of cystitis in rats

Łukasz Dobrek 1 , Zbigniew Arent 2 , Klaudia Nalik-Iwaniak 2 , Kinga Fic 2

1. Andrzej Frycz Modrzewski Krakow University, Department of Pharmacology, Faculty of Medicine and Health Sciences,
2. Experimental and Innovative Medicine Centre, University Centre of Veterinary Medicine UJ-UR, University of Agriculture in Krakow,

Published: 2019-06-11
DOI: 10.5604/01.3001.0013.2414
GICID: 01.3001.0013.2414
Available language versions: en pl
Issue: Postepy Hig Med Dosw 2019; 73 : 282-293

 

Abstract

Aim: Cyclophosphamide (CP) is a cytostatic agent, which evokes numerous side effects, including well-known cystitis. Acrolein released during CP biotransformation exerts both urotoxic and nephrotoxic effects, therefore CP may cause renal dysfunction. The aim of the study was to assess kidney function in experimental models of acute and chronic cystitis. Material/Methods: The studies were carried out on 40 rats (4 groups; n = 10), in which acute (single dose of 150 mg/kg CP; group 2) or chronic (four doses of 75 mg/kg CP; group 4) cystitis was induced with appropriate control groups (group 1 and 3). Renal function was assessed with standard (diuresis, urea, creatinine) and new (fatty acid binding protein – FABP and osteopontin) laboratory parameters as well as histopathologically. Results: The histopathological assessment confirmed the presence of acute and chronic cystitis and did not reveal coexisting significant kidney disorders in groups 2 and 4. Group 2 retained urea and creatinine in the blood. Both groups 2 and 4 showed an increase in diurnal diuresis, and a decreased concentration of urea and creatinine was found in the urine, which was accompanied by significant proteinuria. The daily urinary excretion of small-molecule nitrogen compounds did not differ from the values found in the control groups. In addition, both groups 2 and 4 showed an increase in urinary concentration and excretion of FABP and osteopontin with urine. Conclusions: The experiment revealed the renal dysfunction in the course of cyclophosphamide-induced cystitis with the tubulopathy character, expressed by the increased production and release into the urine two markers reflecting acute kidney injury – FABP and osteopontin.

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