Influence of Cisplatinum on Activated Oxygen Generations by Leukocytes

Abstract

We investigated the activated oxygen generations by leukocytes in the presence of cisplatinum, an antitumor agent, in order to elucidate the influence of cisplatinum on leukocytes function in vitro and in vivo
In the in vitro study, polymorphonuclear leukocytes (PMNs) and monocytes were prepared from a normal volunteer. After stimulation with phorbol myristate acetate (PMA) or opsonized zymosan, activated oxigen generations by PMNs or monocytes were measured by means of chemiluminescence method in the presence or absence of cisplatinum. The concentrations of cisplatinum were adjusted at 0.5, 5.0 and 50μg/ml, and the medium pH also varied at that time. Activated oxygen generations by PMNs and monocytes were reduced significantly in the platinum concentration dependent manner in the pH range from 6.0 to 6.5. On the other hand, in the pH range from 8.3 to 8.8, the activated oxigen generations were not affected by eisplatinum at all.
In the in vivo study, we administered 1.25mg of cisplatinum to male wistar rats intravenously, and prepared whole blood at 4, 12 and 24 hours after administration of cisplatinum. And activated oxigen generations by whole blood were measured in the same manner. The numbers of leukocytes were also counted at the same time. As compared to the control group without administration of cisplatinum, no significant difference was observed in the leukocytes counts at 12 and 24 hours after the administration. However, the activated oxigen generations by whole blood were reduced in the cisplatinum-administration group.
These results indicate that the bactericidal activities of leukocytes were immediately reduced before bone marrow suppression by cisplatinum, and the prevention of acidosis in the patients receiving cisplatinum might be important in order to keep the bactericidal activities of leukocytes.