Comparison of Hypoxic Cell Radiosensitizers, KIN-804, KIN-844,KTN-806 and TX-1877, on Brain and Liver Metabolizing Capacities in Mice Bearing Ehrlich Ascites Carcinoma

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概要

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• The biochemical effects of the 2-nitroimidazole hypoxic cell radiosensitizers KIN-804, KIN-806, and their analogues KIN-844 and TX-1877 on brain acetylcholinesterase (AChE) and hepatic free radical scavenging systems, such as reduced glutathione (GSH) and glucose-6-phosphate dehydrogenase (G-6-PDH) levels, and hepatic antioxidants, such as superoxide dismutase (SOD) and catalase, were evaluated in Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. The assay of brain AChE revealed nonsignificant changes with all drugs examined. To evaluate the hepatic metabolic capacity, groups of mice were divided into control, EAC-inoculated, 10-Gy local gamma-irradiated, and KIN-804, KIN-844, KIN-806, or TX-1877 (50 mg/kg body weight, i.p.) groups, and gamma-irradiation was combined with each drug. EAC inoculation markedly suppressed GSH, G-6-PDH, SOD, and catalase levels. On the other hand, treatment with gamma-irradiation significantly enhanced them. The treatment of EAC-bearing mice with each drug alone in the absence of gamma-irradiation revealed that KIN-806 and its derivative TX-1877 showed antitumor activity through their significant recovery of GSH and SOD levels, respectively, in the EAC-bearing mice group. Similarly, the combined treatment of EAC-bearing mice with gamma-irradiation with each of the drugs tested showed that KIN-806 and TX-1877 significantly increased GSH and SOD, and to a lesser extent G-6-PDH and catalase levels. On the other hand, KIN-804 and KIN-844 had only a nonsignificant effect on all parameters examined. In conclusion, these data reveal that the administration of KIN-806 and TX-1877 with or without subsequent gamma-irradiation, resulted in significant recovery of GSH and SOD activities that were inhibited by EAC inoculation.

• 公益社団法人日本薬学会の論文
• 2002-05-01

著者

• 堀 均

  Division Of Bioinformatics Engineering Department Of Life System Institute Of Technology And Science

• 堀 均

  徳島大学 大学院ソシオテクノサイエンス研究部ライフシステム部門

• NAGASAWA Hideko

  Departmet of Biological Science and Technology, Faculty of Engineering, University of Tokushima

• UTO Yoshihiro

  Departmet of Biological Science and Technology, Faculty of Engineering, University of Tokushima

• HORI Hitoshi

  Departmet of Biological Science and Technology, Faculty of Engineering, University of Tokushima

• Hosoi Hiroshi

  Department Of Biological Science And Technology Faculty Of Engineering University Of Tokushima

• 堀 均

  徳島大学工学部

• 永沢 秀子

  岐阜薬科大学創薬化学大薬化学

• 永沢 秀子

  徳島大学工学部

• Hori Hitoshi

  Department Of Biological Science And Technology Faculty Of Engineering University Of Tokushima

• ABOU-BEDAIR Farid

  Department of Cancer Biology, National Cancer Institute, Cairo University

• ABU-ZEID Medhat

  Department of Cancer Biology, National Cancer Institute, Cairo University

• INAYAMA Seiichi

  Institute of Oriental Medical Sciences

• 稲山 誠一

  Institute Of Oriental Medical Sciences

• 稲山 誠一

  慶應義塾大学医学部薬化学研究所

• Uto Yoshihiro

  Department Of Biological Science And Technology Faculty Of Engineering University Of Tokushima

• Uto Yoshihiro

  Division Of Bioinformatics Engineering Department Of Life System Institute Of Technology And Science

• Abu‐zeid M

  Department Of Cancer Biology National Cancer Institute Cairo University

• Nagasawa H

  Department Of Biological Science And Technology Faculty Of Engineering University Of Tokushima

• Nagasawa Hideko

  Department Of Biological Science And Technology Faculty Of Engineering The University Of Tokushima

• Hori Hitoshi

  Department Of Biochemistry And Molecular Biology Nippon Medical School

• Abou-bedair Farid

  Department Of Cancer Biology National Cancer Institute Cairo University

• Uto Yoshihiro

  Department Of Biological Science And Technology Faculty Of Engineering The University Of Tokushima

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