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 o...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2000, Vol.23 (2), p.190-194
Main Authors: ABU-ZEID, M, HORI, H, NAGASAWA, H, UTO, Y, INAYAMA, S
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carcinoma, Ehrlich Tumor - metabolism
Female
Free Radical Scavengers - pharmacology
Glucosephosphate Dehydrogenase - metabolism
Glucosephosphate Dehydrogenase - radiation effects
Glutathione - metabolism
Glutathione Peroxidase - metabolism
Glutathione Peroxidase - radiation effects
Glutathione Reductase - metabolism
Glutathione Reductase - radiation effects
Hydroxamic Acids - pharmacology
Medical sciences
Mice
Nitroimidazoles - pharmacology
Oxidation-Reduction
Radiation therapy and radiosensitizing agent
Radiation-Sensitizing Agents - pharmacology
Treatment with physical agents
Treatment. General aspects
Tumors
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Summary: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.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.23.190