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

• 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
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.23.190

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.