Studies of methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804) 1: effect on free radical scavenging system in mice bearing Ehrlich ascites carcinoma.

Methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804) is a 2-nitroimidazole derivative containing a hydroxamate side chain designed to enhance the radiosensitization response of hypoxic cells. The possible sensitization of tumor tissue by KIN-804 can be evaluated through investigation of the levels of the free radical scavengers; namely, glutathione (GSH) and its complex enzyme system including glutathione reductase (GR) and glutathione peroxidase (GSH-Px), as well as glucose-6-phosphate dehydrogenase (G-6-PD). Female albino mice were inoculated with Ehrlich carcinoma in the thigh. Administration of KIN-804 (i.p. 80 mg/kg body weight) was carried out 20 min before localized irradiation of 10 Gy. The data revealed that KIN-804 administration, followed or not by gamma irradiation, resulted in a significant decrease in GSH content in tumor tissues associated with inhibition in GR and G-6-PD activities. Blood GSH-Px was enhanced in tumor inoculated mice and the administration of KIN-804 returned it to the normal value. These changes were more noticeable in tumor bearing mice exposed to both KIN-804 and irradiation.
AuthorsM Abu-Zeid, H Hori, H Nagasawa, Y Uto, S Inayama
JournalBiological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 23 Issue 2 Pg. 190-4 (Feb 2000) ISSN: 0918-6158 [Print] JAPAN
PMID10706382 (Publication Type: Journal Article)
Chemical References
  • Free Radical Scavengers
  • Hydroxamic Acids
  • Nitroimidazoles
  • Radiation-Sensitizing Agents
  • 2-nitroimidazole-1-methylacetohydroxamate
  • Glucosephosphate Dehydrogenase
  • Glutathione Peroxidase
  • Glutathione Reductase
  • Glutathione
  • Animals
  • Carcinoma, Ehrlich Tumor (metabolism)
  • Female
  • Free Radical Scavengers (pharmacology)
  • Glucosephosphate Dehydrogenase (metabolism, radiation effects)
  • Glutathione (metabolism)
  • Glutathione Peroxidase (metabolism, radiation effects)
  • Glutathione Reductase (metabolism, radiation effects)
  • Hydroxamic Acids (pharmacology)
  • Mice
  • Nitroimidazoles (pharmacology)
  • Oxidation-Reduction
  • Radiation-Sensitizing Agents (pharmacology)

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