| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1987: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
Cisplatin is one of effective antitumor agents. However, its clinical use has been limited, since it induces nephrotoxicity and ototoxicity. Dopamine has the effect of construction of normal vessels, but dose not construct tumor vessels. In this study, we evaluated that simultaneous administration of cisplatin and dopamine might reduce cisplatin-induced nephrotoxicity and enhance the antitumor effect of cisplatin.
ID_<50> of cisplatin in mice was 15mg/kg. When 15mg/kg of cisplatin was administered in mice with 100mg/kg of ibopamine, an analogue of dopamine, mice survived longer than cisplatin alone. Blood level of cisplatin was higher in administrstion of 15mg/kg of cisplatin and 300mg/kg of ibopamine than that of cisplatin alone. In contrast, concentration of cisplatin in kidneys was lower in administration of cisplatin and ibopamine than that of cisplatin alone. These results suggested that simultaneous administration of cisplatin and ibopamine could reduce cisplatin-induced nephrotoxicity and enhance the antitumor effect of cisplatin in mice.
Children with stage IV neuroblastoma showed various level of urine dopamine. These children were divided into two groups, such as high dopamine group and low dopamine group. No differences were estimated in these two groups on the effect and nephrotoxicity of cisplatin. One child with stage IV neuroblastoma, who had normal level of urine dopamine, was administered with cisplatin and dopamine simultaneously. She complained of palpitation and headache due to dopamine, and nephrotoxicity was detected after administration of cisplatin. These results suggested that dopamine could not enhance the effect of cisplatin and could not reduce cisplatin-induced nephrotoxicity in children.
In summary, simultaneous administration of cisplatin and ibopamine reduced cisplatin-induced nephrotoxicity in mice. However, dopamine could not reduce cisplatin-induced toxicity in children.
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