Comparison of hypoxic cell radiosensitizers, KIN-804, KIN-844, KIN-806 and TX-1877, on brain and liver metabolizing capacities in mice bearing Ehrlich ascites carcinoma.

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.
AuthorsFarid Ahmed Abou-Bedair, Hitoshi Hori, Hideko Nagasawa, Yoshihiro Uto, Medhat Abu-Zeid, Seiichi Inayama
JournalBiological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 25 Issue 5 Pg. 591-6 (May 2002) ISSN: 0918-6158 [Print] Japan
PMID12033498 (Publication Type: Journal Article)
Chemical References
  • 2-nitroimidazole acetamide
  • Free Radical Scavengers
  • Hydroxamic Acids
  • KIN 806
  • KIN 844
  • Nitroimidazoles
  • Radiation-Sensitizing Agents
  • 2-nitroimidazole-1-methylacetohydroxamate
  • Glucosephosphate Dehydrogenase
  • Catalase
  • Superoxide Dismutase
  • Acetylcholinesterase
  • Glutathione
  • Acetylcholinesterase (metabolism)
  • Animals
  • Brain Chemistry (drug effects)
  • Carcinoma, Ehrlich Tumor (metabolism)
  • Catalase (metabolism)
  • Cell Hypoxia (drug effects)
  • Female
  • Free Radical Scavengers (metabolism)
  • Glucosephosphate Dehydrogenase (metabolism)
  • Glutathione (metabolism)
  • Hydroxamic Acids (pharmacology)
  • Liver (drug effects, metabolism)
  • Mice
  • Nitroimidazoles (pharmacology)
  • Radiation-Sensitizing Agents (pharmacology)
  • Superoxide Dismutase (metabolism)
  • Whole-Body Irradiation

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