Reduction of cisplatinum-induced renal toxicity in mice by tetrahydroindazolonecarboxylic acid (HIDA) [corrected].
The ability of tetrahydroindazolone carboxylic acid (HIDA) to reduce the toxicity of cis-diamminedichloroplatinum (cis-DDP) in CDF1 mice was investigated. Toxicity was assessed both in terms of mouse lethality occurring within 14 days after treatment and kidney damage estimated by measurement of plasma urea. The levels of plasma urea were found to increase from day 2 after intraperitoneal (i.p.) injection of cis-DDP, reaching a peak at day 5. This increase was also cis-DDP-dose dependent. An i.p. injection of HIDA reduced kidney damage only when given 2.5 h prior to cis-DDP and at HIDA doses of 100 mg/kg or larger. The protection ratio for this reduction was 1.10. HIDA also decreased mouse lethality from cis-DDP, resulting in a PR of 1.41. This protective effect of HIDA on cis-DDP toxicity may eventually have a clinical application.
Radacic
M
M
Department of Experimental Clinical Oncology, Danish Cancer Society, Aarhus.
Overgaard
J
J
Skaric
D
D
Skaric
V
V
Horsman
M
M
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007191:Indazoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D014508:Urea / Q000097:blood
D007191:Indazoles; C051797:4,5,6,7-tetrahydro-3-oxo-2H-indazole-5,5-dicarboxylic acid; D014508:Urea; D002945:Cisplatin