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.