Protective effect of carboxyethylgermanium sesquioxide (Ge-132) on superoxide generation by 60Co-irradiated leukocytes.

Abstract

The carboxyethylgermanium sesquioxide, Ge-132, is an organogermanium compound which has been shown to modulate leukocyte functions. In this study, we examined the effect of Ge-132 on the generation of superoxide radicals (O2-) either from leukocytes or in cell-free system, employing the highly sensitive 2-methyl-6-[p-methoxy-phenyl]-3,7-dihydroimidazo[1,2-alpha]pyra zin-3-one (MCLA)-dependent chemiluminescence method and the specific electron spin resonance/spin trapping method, respectively. In addition, the in vitro protective effect of Ge-132 on the leukocytes irradiated with 60Co was studied. The incubation with Ge-132 resulted in an increase in basal O2- release of intact leukocytes, but had no effect on O2- generation from leukocytes stimulated with phorbol myristate acetate (PMA). Irradiation with 60Co decreased the O2- generation from leukocytes in a dose-dependent manner. Ge-132 had no effect on basal O2- release from 60Co-irradiated leukocytes, but it prevented the decrease in PMA-stimulated O2- generation by irradiated leukocytes. Ge-132 itself had no superoxide scavenging activity in cell-free system. On the other hand, higher concentrations of Ge-132 had decreasing effects on both basal O2- release and PMA-stimulated O2- generation from leukocytes, but they did not affect leukocyte viability. Above results indicate that 1) Ge-132 can stimulate the basal O2- release from leukocytes, 2) Ge-132 can prevent the decrease of O2- generation by 60Co-irradiated leukocytes, 3) in higher concentrations, Ge-132 may have a membrane stabilizing effect.