1987 Fiscal Year Final Research Report Summary
Reduction of adverse effects of cisplatin by macrocyclic polyamines
| Project/Area Number |
61570761
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | Shinshu University School of Medicine |
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Principal Investigator |
OGAWA Akimi Professor of Urology, Shinshu University School of Medicine, 医学部, 教授 (10009954)
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| Co-Investigator(Kenkyū-buntansha) |
中本 富夫 信州大学, 医学部, 助手 (10135139)
全田 浩 信州大学, 医学部附属病院, 教授 (60135150)
ZENDA Hiroshi Professor, Department of Pharmacy, Shinshu University Hospital (60135150)
NAKAMOTO Tomio Assistant of Urology, Shinshu University School of Medicine (10135139)
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| Project Period (FY) |
1986 – 1987
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| Keywords | Macrocyclic polyamine / Cisplatin / 抗癌剤副作用 |
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| Research Abstract |
We studied in rats whether macrocyclic polyamines given simultaneously with cisplatin can reduce the toxicity of cisplatin. Five kinds of macrocyclic polyamines and a total of 263 rats were used.
1) 2,2,2-tetramine 4 HCL, cyclam, 2,2,2,2-pentamine and 2,3,2-tetramine were inappropriate for use, because when given in high doses they killed all rats owing to their own toxicity and when given in low doses they did not suppress the lethal effect of cisplatin.
2) Dioxocyclam alone was given in doses up to 228 mg/Kg (30-fold moles of 10 mg/Kg of cisplatin) and almost all rats survived. When 10 mg/Kg (lethal dosis) of cisplatin was given and followed by 3-fold moles of dioxocyclam, 24% of rats survived, by 6-fold moles 20% survived, by 10-fold moles 36% survived and by 30-fold moles 24% survived. Therefore, dioxocyclam seemed to reduce the lethal effect of cisplatin.
3) When cisplatin 10 mg/Kg was given and followed by 6-fold moles of dioxocyclam and sodium thiosulfate 200 mg/Kg, 45% of rats survived. When the dosis of dioxocyclam increased to 10-fold moles in the same experiment, 67% of rats survived. Addition of sodium thiosulfate seemed to enhance the anticisplatin effect of dioxocyclam.
4) Urinary excretion of platinum for the first 4 days did not differ significantly among rats given cisplatin alone, rats given cisplatin and dioxocyclam andrats given cisplatin, dioxocyclam and sodium thiosulfate. These results indicate that dioxocyclam with sodium thiosulfate can reduce the toxic effects of cisplatin.
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