Protective Effect of Several Metals Against cis-Diamminedichloroplatinum Toxicity to Mouse Survival and Kidney

Cho, Yong Hyun; Yoon, Moon Soo

Abstract

cis-Diamminedichloroplatinum(Cisplatin ; CDDP) intoxication has been known to be prevented by decrease of toxicity using pretreatment with small doses of some metals. In this study, 12 weeks of age, weighing approximately 30 gram male mature I.C.R. mice were used to investigate protective mechanism of combined treatment or pretreatment with small doses of metals(Cu, Se, Zn) against CDDP intoxication, and in the group treated with metals : 1. Survival effects against lethal dose of CDDP were observed and 2. The effects on the renal toxicity with administrating one third of lethal CDDP dose were observed by different preventive effect among each pretreated metals with blood chemistry, kidney weight and histopathologic finding, and we obtained the results as follows : 1. 15 days survival rates after administration of lethal CDDP dose were significantly increased in the group selenium combined treatment and in the copper combined treatment group compared to the group without combined treatment of metal. 2. At the day after administration of one third of lethal CDDP dose, BUN levels were significantly increased in the group without pretreatment and in the zinc pretreatment group compared to control group, but they were not increased in cases of pretreatment with selenium or copper, and serum creatinine levels were not significantly changed in the all experimental groups compared to control group. 3. At 5th day after administration of one third of lethal CDDP dose, relative kidney weights(kidney weight/body weight) were significantly increased in the group without pretreatment and in the zinc pretreatment group compared to control group, but they were not significantly increased in the pretreated group with selenium or copper. 4. At 5th day after administration of one third of lethal CDDP dose, renal histopathologic findings showed vacuolar changes and focal necrosis of proximal tubular cells at the corticomedullary junction in the group without pretreatment and in the zinc pretreatment group, but only swelling of those area in the selenium or copper pretreated group. 5 At 15th day after administration of one third of lethal CDDP dose, BUN levels, serum creatinine levels and relative kidney weights(kidney weight/body weight) were not significantly different between the all pretreated group and control group, and histopathologic findings also did not reveal any differences between the heavy metal pretreated group and control group.