[Dose effects on vital parameters of guinea pig by continuous administration of cisplatin]

A wide used anti-neoplasmic agent, cisplatin (CDDP), injures normal organs dose-dependently by its toxicity. The mechanisms of organ injuries have been studied to prevent and rescue patient conditions. We analyzed the relation between CDDP doses and onset of organ injuries to clarify the mechanism of CDDP toxicity. The onset doses to cause organ injuries were calculated using weekly collected vital parameters of 18 male guinea pigs which were injected CDDP (2 mg/kg/day, 5 times/week) intraperitonealy until the death of animals. Correlations between the values of vital parameters and CDDP doses and applicative survival curve method were used to estimate the onset doses. Abnormal changes in iron metabolism and auditory organ were first noted at 10.2 mg/body and 10.8 mg/body of CDDP, respectively. The change in the salivary glands were noted at 15 mg/body. Renal injury started at 19.5 mg/body, and damages to the bone marrow started between 19.7 mg/body to 33.6 mg/body of CDDP. The minimal dose of liver dysfunction was 21.3 mg/body. It is concluded from these results that 1) the onset of organ injury depends on the dose of CDDP, and 2) the order of such injuries was iron metabolism, auditory organ, the salivary glands, kidney, the bone marrow, and the liver in guinea pigs, 3) Other organ injuries might be detected to clarify hearing levels during chemotherapy because those were noted following auditory damage except iron metabolism.