Mizushima Y, Sassa K, Hamazaki T, Fujishita T, Oosaki R, Kobayashi M
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Br J Cancer. 1998 Oct;78(8):1030-4. doi: 10.1038/bjc.1998.623.
When cyclophosphamide (CY) (100-120 mg kg(-1)) was administered intravenously (i.v.) to normal F-344 rats, oliguria occurred over the 5-day observation period. Conversely, in rats bearing matrix metalloproteinase-9 (MMP-9) producing 13762NF mammary adenocarcinoma (MTLn3 clone), polyuria occurred chiefly during the first 24 h after CY treatment. In parallel with urine volume, a decrease in the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) was observed during the first 5 days after CY treatment in normal rats, but it increased in MTLn3-bearing rats. No elevation in blood urea nitrogen (BUN) or serum creatinine (Cr) values was observed for either group. Both urine volume and urinary excretion of NAG after CY treatment were lower in rats bearing the MTC clone (lower production of MMP-9) than for those bearing the MTLn3 clone. In the case of treatment with cisplatin (CDDP, 4-6 mg kg(-1)), urine volume, urinary NAG excretion and BUN and serum Cr values all increased in normal rats and were all found to be higher in MTLn3-bearing rats than in normal rats. The diuretic response to these drugs in tumour-bearing (TB) rats may be associated with MMP-9 produced by the tumour cells. This report suggests that the nephrotoxicity due to anti-cancer drugs may change when the drugs are used for the treatment of patients bearing a MMP-9-producing tumour.
当向正常的F-344大鼠静脉注射（i.v.）环磷酰胺（CY）（100 - 120 mg kg⁻¹）时，在5天的观察期内出现少尿。相反，在携带产生基质金属蛋白酶-9（MMP-9）的13762NF乳腺腺癌（MTLn3克隆）的大鼠中，多尿主要发生在CY治疗后的最初24小时内。与尿量平行，在正常大鼠中，CY治疗后的前5天观察到N-乙酰-β-D-氨基葡萄糖苷酶（NAG）的尿排泄量减少，但在携带MTLn3的大鼠中其增加。两组的血尿素氮（BUN）或血清肌酐（Cr）值均未升高。携带MTC克隆（MMP-9产生量较低）的大鼠在CY治疗后的尿量和NAG尿排泄量均低于携带MTLn3克隆的大鼠。在用顺铂（CDDP，4 - 6 mg kg⁻¹）治疗的情况下，正常大鼠的尿量、尿NAG排泄量以及BUN和血清Cr值均增加，并且发现携带MTLn3的大鼠中的这些值均高于正常大鼠。荷瘤（TB）大鼠对这些药物的利尿反应可能与肿瘤细胞产生的MMP-9有关。本报告表明，当抗癌药物用于治疗携带产生MMP-9肿瘤的患者时，其肾毒性可能会发生变化。
