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The influence of oxazaphosphorine agents on kidney function in rats
Łukasz Dobrek1, Beata Skowron1, Agnieszka Baranowska1
1Department of Pathophysiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.
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 75mg/kg b.w. of CP), and group 3 (treated with 60mg/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.
Insights
Cyclophosphamide (CP) and ifosfamide (IF) chemotherapy can harm kidneys. CP caused more kidney dysfunction and potential acute kidney injury in rats, while IF caused less severe effects, with neither drug showing kidney damage histologically.
Area of Science:
- Nephrology
- Toxicology
- Pharmacology
Background:
- Cytostatic oxazaphosphorines like cyclophosphamide (CP) and ifosfamide (IF) are associated with kidney damage.
- The clinical presentation and severity of kidney damage vary based on the drug, dose, and administration route.
Purpose of the Study:
- To assess the impact of CP and IF on kidney histology and function in rats.
- To compare the nephrotoxic effects of CP and IF following intraperitoneal administration.
Main Methods:
- Thirty rats were divided into control, CP-treated (75mg/kg), and IF-treated (60mg/kg) groups.
- Kidney function was evaluated by measuring urine and plasma parameters, including neutrophil gelatinase-associated lipocalin-1 (NGAL-1).
- Histopathological examination of kidneys was performed.
Main Results:
- CP-treated rats exhibited polyuria, decreased urine pH, reduced urinary excretion of electrolytes and urea, and increased NGAL-1 excretion.
- CP treatment also led to decreased plasma uric acid concentration.
- IF-treated rats showed decreased urine pH but generally normal urinary excretion, with reduced uric acid excretion and no histopathological abnormalities.
Conclusions:
- CP induced more significant kidney dysfunction, with indicators suggesting prerenal acute kidney injury.
- Disturbances in uric acid excretion and plasma levels in CP-treated rats may indicate increased oxidative stress and the kidney's compensatory antioxidant mechanisms.
- Neither CP nor IF caused observable histopathological kidney damage in the study.
- CP appears to be more nephrotoxic than IF at the tested doses.
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