The influence of oxazaphosphorine agents on kidney function in rats

Background and objective: The application of cytostatic oxazaphosphorines such as cyclophosphamide (CP) and ifosfamide (IF) is associated with the risk of kidney damage that, depending on the type of drug, dose and route of administration, adopts a different clinical entity and severity. The aim of...

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Main Authors: Łukasz Dobrek, Beata Skowron, Agnieszka Baranowska, Klaudia Płoszaj, Dorota Bądziul, Piotr Thor
Format: Article
Language:English
Published: MDPI AG 2017-07-01
Series:Medicina
Subjects:
Online Access:https://www.mdpi.com/1010-660X/53/3/179
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author Łukasz Dobrek
Beata Skowron
Agnieszka Baranowska
Klaudia Płoszaj
Dorota Bądziul
Piotr Thor
author_facet Łukasz Dobrek
Beata Skowron
Agnieszka Baranowska
Klaudia Płoszaj
Dorota Bądziul
Piotr Thor
author_sort Łukasz Dobrek
collection DOAJ
description Background and objective: The application of cytostatic oxazaphosphorines such as cyclophosphamide (CP) and ifosfamide (IF) is associated with the risk of kidney damage that, depending on the type of drug, dose and route of administration, adopts a different clinical entity and severity. The aim of our study was to assess the influence of CP and IF on the kidney histology and function in rats intraperitoneally treated with four doses of either CP or IF. Materials and methods: A total of 30 rats were divided into three groups (10 in each group): group 1 (control), sham treated with saline solution, group 2 (treated with 75 mg/kg b.w. of CP), and group 3 (treated with 60 mg/kg b.w. of IF). After the treatment rats were sacrificed, blood was collected and nephrectomy and cystectomy were performed. Qualitative and quantitative parameters (including neutrophil gelatinase-associated lipocalin-1, NGAL-1) of kidney function were assayed in urine and plasma. Results: CP-treated rats were characterized by a significant polyuria, decreased urine pH and by decreased daily urinary excretion of sodium, potassium, urea and uric acid accompanied by increased NGAL-1 excretion. A significant decrease of the plasma uric acid concentration was also observed. IF-treated animals were also characterized by decreased urine pH but with normal daily urinary excretion of assessed substances (except for reduced uric acid excretion). Both CP and IF treated rats did not show any histopathological abnormalities in their kidneys. Conclusions: CP caused more advanced kidney dysfunction and some indices suggested the development of prerenal acute kidney injury. In the CP-treated group some particularly marked urinary and plasma uric acid disturbances suggested compensation of increased oxidative stress as uric acid is considered to exert also antioxidant properties.
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spelling doaj.art-5df88e48e5c44af4acb813554a9f43402023-09-02T01:48:45ZengMDPI AGMedicina1010-660X2017-07-0153317918910.1016/j.medici.2017.05.004j.medici.2017.05.004The influence of oxazaphosphorine agents on kidney function in ratsŁukasz Dobrek0Beata Skowron1Agnieszka Baranowska2Klaudia Płoszaj3Dorota Bądziul4Piotr Thor5Department of Pathophysiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, PolandDepartment of Pathophysiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, PolandDepartment of Pathophysiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, PolandMedical analytics graduate student, Jagiellonian University Medical College, Krakow, PolandDepartment of Human Physiology and Pathophysiology, Faculty of Medicine, University of Rzeszów, Rzeszow, PolandDepartment of Pathophysiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, PolandBackground and objective: The application of cytostatic oxazaphosphorines such as cyclophosphamide (CP) and ifosfamide (IF) is associated with the risk of kidney damage that, depending on the type of drug, dose and route of administration, adopts a different clinical entity and severity. The aim of our study was to assess the influence of CP and IF on the kidney histology and function in rats intraperitoneally treated with four doses of either CP or IF. Materials and methods: A total of 30 rats were divided into three groups (10 in each group): group 1 (control), sham treated with saline solution, group 2 (treated with 75 mg/kg b.w. of CP), and group 3 (treated with 60 mg/kg b.w. of IF). After the treatment rats were sacrificed, blood was collected and nephrectomy and cystectomy were performed. Qualitative and quantitative parameters (including neutrophil gelatinase-associated lipocalin-1, NGAL-1) of kidney function were assayed in urine and plasma. Results: CP-treated rats were characterized by a significant polyuria, decreased urine pH and by decreased daily urinary excretion of sodium, potassium, urea and uric acid accompanied by increased NGAL-1 excretion. A significant decrease of the plasma uric acid concentration was also observed. IF-treated animals were also characterized by decreased urine pH but with normal daily urinary excretion of assessed substances (except for reduced uric acid excretion). Both CP and IF treated rats did not show any histopathological abnormalities in their kidneys. Conclusions: CP caused more advanced kidney dysfunction and some indices suggested the development of prerenal acute kidney injury. In the CP-treated group some particularly marked urinary and plasma uric acid disturbances suggested compensation of increased oxidative stress as uric acid is considered to exert also antioxidant properties.https://www.mdpi.com/1010-660X/53/3/179CyclophosphamideIfosfamideKidneyNephrotoxicityRats
spellingShingle Łukasz Dobrek
Beata Skowron
Agnieszka Baranowska
Klaudia Płoszaj
Dorota Bądziul
Piotr Thor
The influence of oxazaphosphorine agents on kidney function in rats
Medicina
Cyclophosphamide
Ifosfamide
Kidney
Nephrotoxicity
Rats
title The influence of oxazaphosphorine agents on kidney function in rats
title_full The influence of oxazaphosphorine agents on kidney function in rats
title_fullStr The influence of oxazaphosphorine agents on kidney function in rats
title_full_unstemmed The influence of oxazaphosphorine agents on kidney function in rats
title_short The influence of oxazaphosphorine agents on kidney function in rats
title_sort influence of oxazaphosphorine agents on kidney function in rats
topic Cyclophosphamide
Ifosfamide
Kidney
Nephrotoxicity
Rats
url https://www.mdpi.com/1010-660X/53/3/179
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