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] pyrazin-3-one (MCLA) -dependent chemiluminescence method and the specific electron spin resonance/spin trapping method, respectively. In addition, thein vitro protective effect of Ge-132 on the leukocytes irradiated with60Co was studied.
The incubation with Ge-132 resulted in an increase in basal O2 − release of intact leukocytes, but had no effect on OZ generation from leukocytes stimulated with phorbol myristate acetate (PMA). Irradiation with60Co decreased the Oz generation from leukocytes in a dose-dependent manner. Ge-132 had no effect on basal O2 − release from60Co-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 −1 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 by60Co-irradiated leukocytes, 3) in higher concentrations, Ge-132 may have a membrane stabilizing effect.
Similar content being viewed by others
References
Tsusui M, Kakimoto N, Axtell DD, Oikawa H, Asai K. Crystal structure of carboxyethylgermanium sesquioxide. J Am Chem Soc 1976; 98: 8287–9.
Suzuki F, Brutkiewicz RR, Pollard RB. Importance of T-cell and macrophages in the antitumor activity of carboxyethylgermanium sesquioxide (Ge-132). Anticancer Research 1985; 5: 479–84.
Suzuki F, Brutkiewicz RR, Pollard RB. Ability of sera from mice treated with Ge-132, an organic germanium compound, to inhibit experimental murine ascites tumors. Br J Cancer 1985; 52: 757–63.
Brutkiewicz RR, Suzuki F. Bilogical activities and antitumor mechanism of an immunopotentiating organogermanium compound, Ge-132 (Review).In Vivo 1987; 1: 189–204.
Munakata T, Arai S, Kuwano K, Furukawa M, Tomita Y. Induction of interferon production by natural killer cells by organo-germanium compound, Ge-132. J Interferon Res 1987; 7: 69–76.
Fukuhara M, Oda K, Hara M, Nakata Y, Takahashi I, Kimura I. The effect of Ge-132 on the chemiluminescence of neutrophils (compared with HLBI). Report of the 9th Germanium Symposium, Tokyo: Asai Germanium Co, 1983: 15–21. (In Japanese)
Nishida A, Kimura H, Nakano M. High Sensitive and specific method for estimating the ability of human granulocytes and monocytes to generate O2 −: chemiluminescence probe with 2-methyl-6[p-methoxyphenyl]3,7-dihydroimidazo[1,2-a]pyrazin-3-one. In: Hayaishi O, Niki E, Kondo M, Yoshikawa T, eds. Medical, biochemical and chemical aspects of free radicals. Amsterdam: Elsevier Science Publishers, 1989: 877–81.
Prónai L, Arimori S, Nakazawa H. Superoxide scavenging activity of BG-104 before and after sonification — determined by ESR spin trapping method. Biotherapy 1990; 2: 63–8.
West MA. Role of cytokines in leukocyte activation: phagocytic cells. In: Kleinzeller A, ed. Current topics in membrane and transport. San Diego: Academic Press, 1990: 537–70.
Nakamura K, Endo H, Kashiwazaki S. Serum oxidative activities and rheumatoid arthritis. Int J Tiss Reac 1987; 9: 307–16.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Prónai, L., Arimori, S. Protective effect of carboxyethylgermanium sesquioxide (Ge-132) on superoxide generation by60Co-irradiated leukocytes. Biotherapy 3, 273–279 (1991). https://doi.org/10.1007/BF02171692
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02171692