Hardie E M, Page R L, Hoopes P J
College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
J Appl Toxicol. 1992 Oct;12(5):369-75. doi: 10.1002/jat.2550120514.
The purpose of this study was to examine if ATP-MgCl2, an agent that protects against acute cisplatin toxicity in vitro, protected against cisplatin toxicity in vivo. Baseline renal function measurements were obtained on dogs (n = 12) and rats (n = 20) on day -1. Dogs were given 90 mg m-2 cisplatin (n = 5), 90 mg m-2 cisplatin and 50 mumol kg-1 ATP-MgCl2 (n = 5), or 90 mg m-2 cisplatin and 150 mumol kg-1 ATP-MgCl2 (n = 2), in a slow bolus i.v. injection on day 0. Rats were given 4 mg kg-1 cisplatin i.p. (n = 6) and 25 mumol kg ATP-MgCl2 (n = 8) i.v. or 4 mg kg-1 cisplatin i.p. and 25 mumol kg-1 ATP-MgCl2 (n = 6) i.v. on day 0. Renal function was assessed on a routine basis for 14 days. All dogs had significantly decreased creatinine clearance following cisplatin administration. There were no significant differences in renal function tests between groups of dogs. One dog given 50 mumol kg-1 ATP-MgCl2 and both dogs given 150 mumol kg-1 ATP-MgCl2 in addition to cisplatin developed acute anuric renal failure and were euthanatized prior to completion of the study. Rats given 4 mg kg-1 cisplatin and 25 mumol kg-1 ATP-MgCl2 had significantly increased blood urea nitrogen and serum creatinine after drug administration, compared to rats given cisplatin alone. The results indicated that ATP-MgCl2 worsened in vivo cisplatin renal toxicity in the dog and rat.
本研究的目的是检验ATP - MgCl₂（一种在体外可预防顺铂急性毒性的药物）在体内是否也能预防顺铂毒性。在第 -1天对犬（n = 12）和大鼠（n = 20）进行基线肾功能测量。在第0天，犬通过静脉缓慢推注分别给予90 mg m⁻²顺铂（n = 5）、90 mg m⁻²顺铂加50 μmol kg⁻¹ ATP - MgCl₂（n = 5）或90 mg m⁻²顺铂加150 μmol kg⁻¹ ATP - MgCl₂（n = 2）。大鼠在第0天腹腔注射4 mg kg⁻¹顺铂（n = 6）并静脉注射25 μmol kg ATP - MgCl₂（n = 8），或腹腔注射4 mg kg⁻¹顺铂并静脉注射25 μmol kg⁻¹ ATP - MgCl₂（n = 6）。连续14天定期评估肾功能。所有犬在给予顺铂后肌酐清除率均显著降低。各犬组之间的肾功能测试无显著差异。一只给予50 μmol kg⁻¹ ATP - MgCl₂以及两只给予150 μmol kg⁻¹ ATP - MgCl₂（均为顺铂加ATP - MgCl₂）的犬发生了急性无尿性肾衰竭，并在研究完成前实施了安乐死。与仅给予顺铂的大鼠相比，给予4 mg kg⁻¹顺铂和25 μmol kg⁻¹ ATP - MgCl₂的大鼠在给药后血尿素氮和血清肌酐显著升高。结果表明，ATP - MgCl₂使犬和大鼠体内顺铂的肾毒性恶化。
