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Effects of Phenobarbital and Endotoxin on the Lethality and Metabolism of 6-Mercaptopurine in Male BALB/c Mice¹

Department of Internal Medicine, Shiga Center for Adult Diseases, 328 Moriyama, Moriyama, Shiga, 524 Japan [T. H.], and The First Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, Kyoto, 606 Japan [T. N., H. U.]

In male BALB/c mice, a combination of individually nonlethal doses of 6-mercaptopurine and endotoxin was significantly lethal. In contrast, mice treated with phenobarbital were resistant to this lethal effect. The high levels of thioinosinic acid in mice that were treated with endotoxin contrasted significantly with the levels in phenobarbital-treated mice. On the other hand, the concentration of hypoxanthine was increased by the administration of phenobarbital and decreased by the administration of endotoxin. The sleeping time and levels of pentobarbital hydoxylase found in endotoxin-treated mice were consistent with the lethality and levels of thioinosinic acid. After mice were treated with endotoxin, their sleeping time was prolonged, which agrees with the course of the stimulatory effects of 6-mercaptopurine anabolism. However, there were no significant differences in hypoxanthine-guanine phosphoribosyltransferase. Furthermore, contrary to expectation, there were significant increases in xanthine oxidase after treatment with endotoxin. Thus, the metabolism of 6-mercaptopurine might be modified by hepatic microsomal enzyme activity.

¹ Supported in part by a grant-in-aid for Scientific Research from the Ministry of Education and the Ministry of Health and Welfare of Japan.

Received 1/ 6/77. Accepted 5/11/77.