Dobrek Lukasz, Nalik-Iwaniak Klaudia, Fic Kinga, Arent Zbigniew
Department of Clinical Pharmacology, Wroclaw Medical University, Wroclaw, Poland.
Experimental and Innovative Medicine Centre, University Centre of Veterinary Medicine UJ-UR, University of Agriculture in Krakow, Krakow, Poland.
Curr Urol. 2020 Oct;14(3):150-162. doi: 10.1159/000499245. Epub 2020 Oct 13.
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.
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.
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.
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.
尿路毒性是环磷酰胺和异环磷酰胺的一个典型特性。乙酰半胱氨酸被视为一种具有尿路保护作用且可能具有肾保护作用的化合物。本研究的目的是评估乙酰半胱氨酸治疗对环磷酰胺或异环磷酰胺诱导膀胱炎的大鼠肾脏和膀胱形态以及肾功能的影响。
分别通过五次给予环磷酰胺（75毫克/千克）或异环磷酰胺（80毫克/千克），诱导第2组和第3组以及第4组和第5组的大鼠患膀胱炎。此外，第3组和第5组接受乙酰半胱氨酸（200毫克/千克）治疗。第1组作为对照进行“假处理”。实验结束后，对动物实施安乐死，并收集其肾脏和膀胱用于组织病理学分析。肾功能评估基于经典的血液氮参数（尿素、肌酐和尿酸），以及蛋白尿、胱抑素C（CysC）和肾损伤分子-1（KIM-1）的尿浓度，及其24小时尿排泄量。
在第2组和第4组中观察到血尿素氮和尿酸降低、尿pH值降低，同时CysC和KIM-1的尿浓度显著升高，及其24小时尿排泄量增加。乙酰半胱氨酸治疗未引起血液参数的显著变化，但显著降低了CysC和KIM-1的24小时尿排泄量，并减轻了膀胱的组织病理学异常，对肾脏结构无显著影响。
在环磷酰胺和异环磷酰胺诱导膀胱炎的实验模型中使用的乙酰半胱氨酸具有尿路保护作用，还减轻了肾功能障碍，这表明其在环磷酰胺/异环磷酰胺治疗中作为肾保护化合物具有潜在用途。
