<b><i>Introduction</i></b>: Urotoxicity is a characteristic attribute of cy-clophosphamide and ifosfamide. Acetylcysteine is perceived as a uroprotective and possible nephroprotective compound. The purpose of the study was to assess the effect of acetylcysteine treatment on the morphology of the kidneys and the urinary bladder, and renal function in rats with cystitis induced by cyclophosphamide or ifosfamide. <b><i>Methods</i></b>: Cystitis was induced in rats belonging to groups 2 and 3, as well as 4 and 5, by five administrations of cyclophosphamide (75 mg/kg) or ifosfamide (80 mg/kg) respectively. Additionally, groups 3 and 5 received acetylcysteine (200 mg/kg). Group 1 was “sham treated” as a control. Upon conclusion of the experiment, the animals were euthanized and their kidneys and urinary bladders were collected for histopathological analysis. The assessment of renal function was based on classic nitrogen blood parameters (urea, creatinine, and uric acid), as well as proteinuria and cystatin C (CysC) and kidney injury molecule-1 (KIM-1) urinary concentrations, and their 24-hour elimination with urine. <b><i>Results</i></b>: Reduction of blood urea nitrogen and uric acid, and urinary pH with a significant increase of CysC and KIM-1 urinary concentrations, and their 24-hour elimination with urine were observed in groups 2 and 4. The acetylcysteine treatment did not cause a significant change of blood parameters, but significantly decreased 24-hour elimination of CysC and KIM-1 with urine, and accounted for alleviation of the histopathological abnormalities of urinary bladders, with no significant effects on the structure of the kidneys. <b><i>Conclusions</i></b>: Acetylcysteine used in the experimental model of cyclophosphamide- and ifosfamide-induced cystitis had a uroprotective effect and also reduced renal dysfunction, which suggests its potential use as a nephroprotective compound in cyclophosphamide/ifosfamide therapy.

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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.

AbstractIntroductionIfosfamide (IF) is a cytostatic that exhibits adverse nephrotoxic properties. Clinically, IF-induced nephrotoxicity takes various forms, depending on applied dose and length of treatment.ObjectivesThe aim of the study was to evaluate the two proteins: osteopontin (OP) and fatty acid binding protein (FABP), as markers of kidney function in rats treated with ifosfamide.Material and MethodsRats receiving a single IF dose (250 mg/kg b.w.; group 1) or treated with five consecutive IF doses administrated on following days (50mg/kg b.w.; group 3), compared with control groups 2 and 4, respectively, were studied. Kidney function was assessed using classical (urea, creatinine) and novel (FABP, OP) laboratory parameters and by histopathology.ResultsSingle IF dose administration resulted in significant total proteinuria with urinary concentrations and 24-hour excretions of both FABP and OP comparable to the appropriate control. In rats treated with five consecutive IF doses, the urinary concentrations and 24-hour excretion of both FABP and OP were significantly higher compared to the appropriate control. The development of cystitis was revealed in groups 1 and 3, which was not accompanied by significant histopathological kidney damage.ConclusionsBoth OP and FABP may be useful laboratory markers of tubulopathy in the early stage of chronic nephrotoxicity of ifosfamide.

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.