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ATP‐mgcl 2 increases cisplatin toxicity in the dog and rat
Author(s) -
Hardie Elizabeth M.,
Page Rodney L.,
Hoopes P. Jack
Publication year - 1992
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550120514
Subject(s) - cisplatin , toxicity , creatinine , chemistry , renal function , urea , blood urea nitrogen , bolus (digestion) , in vivo , pharmacology , endocrinology , medicine , biochemistry , chemotherapy , biology , microbiology and biotechnology
The purpose of this study was to examine if ATP‐MgCl 2 , 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 μmol kg −1 ATP‐MgCl 2 ( n = 5), or 90 mg m −2 cisplatin and 150 μmol kg −1 ATP‐MgCl 2 ( n = 2), in a slow bolus i.v. injection on day 0, Rats were given 4 mg kg −1 cispiatin i.p. ( n = 6) and 25 μmol kg ATP‐MgCl 2 ( n = 8) i.v. or 4 mg kg −1 cisplatin i.p. and 25 μmol kg −1 ATP‐MgCl 2 ( n = 6) i.v. on day 0. Renal function was assessed on a routine basis for 14 days. All dogs had significantly decreased creatinine ciearance following cisplatin administration. There were no significant differences in renal function tests between groups of dogs. One dog given 50 μmol kg −1 ATP‐MgCl 2 and both dogs given 150 μmol kg −1 ATP‐MgCl 2 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 μmol kg −1 ATP‐MgCl 2 had significantly increased blood urea nitrogen and serum creatinine after drug administration, compared to rats given cisplatin alone. The results indicated that ATP‐MgCl 2 worsened in vivo cisplatin renal toxicity in the dog and rat.