Dobrek Łukasz, Arent Zbigniew, Nalik-Iwaniak Klaudia, Fic Kinga, Kopańska Marta
Independent Researcher cooperating with Experimental and Innovative Medicine Centre, University Centre of Veterinary Medicine UJ-UR, University of Agriculture in Krakow, Krakow Poland.
Department of Human Physiology, Faculty of Medicine, University of Rzeszow, Rzeszow Poland.
Open Med (Wars). 2019 Jul 19;14:561-571. doi: 10.1515/med-2019-0063. eCollection 2019.
Ifosfamide (IF) is a cytostatic that exhibits adverse nephrotoxic properties. Clinically, IF-induced nephrotoxicity takes various forms, depending on applied dose and length of treatment.
The 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.
Rats 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.
Single 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.
Both OP and FABP may be useful laboratory markers of tubulopathy in the early stage of chronic nephrotoxicity of ifosfamide.
异环磷酰胺(IF)是一种具有肾毒性不良反应的细胞抑制剂。临床上,IF诱导的肾毒性有多种形式,这取决于应用剂量和治疗时长。
本研究旨在评估骨桥蛋白(OP)和脂肪酸结合蛋白(FABP)这两种蛋白,作为异环磷酰胺治疗大鼠肾功能的标志物。
分别研究了接受单次IF剂量(250mg/kg体重;第1组)或连续5天接受IF剂量治疗(50mg/kg体重;第3组)的大鼠,分别与对照组2和4进行比较。使用经典的(尿素、肌酐)和新的(FABP、OP)实验室参数以及组织病理学评估肾功能。
单次给予IF剂量导致显著的总蛋白尿,FABP和OP的尿浓度及24小时排泄量与相应对照组相当。在连续5次给予IF剂量治疗的大鼠中,FABP和OP的尿浓度及24小时排泄量均显著高于相应对照组。第1组和第3组出现膀胱炎,且未伴有明显的肾脏组织病理学损伤。
OP和FABP均可能是异环磷酰胺慢性肾毒性早期肾小管病变的有用实验室标志物。