Skip to main content
Log in

Decreased plasma superoxide scavenging activity in immunological disorders — carboxyethylgermanium sesquioxide (Ge-132) as a promoter of prednisolone

  • Published:
Biotherapy

Summary

We investigated so-called superoxide scavenging activity (SSA) of plasma in patients with several immunological disorders, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), polymyo-dermatomyositis (PM), progressive systemic sclerosis (PSS), myasthenia gravis (MG) and autoimmune thyroid disease (AT), using the electron paramagnetic resonance/spin trapping technique. Since carboxyethylgermanium sesquioxide, Ge-132, has been reported to modulate both the immune response and leukocyte functions, we have studiedin vivo effect of Ge-132 on plasma SSA and other laboratory parameters in these disorders. The plasma SSA was significantly lower in RA, SLE, PM and PSS, but not in MG and AT, as compared with that in healthy controls. An inverse correlation was observed between plasma SSA and parameters such as erythrocytes sedimentation rates, absolute number of leukocytes, C-reactive protein and serum globulin levels. Furthermore, plasma SSA was significantly decreased in rheumatoid factor-positive patients as compared to negative patients. No correlation was observed between plasma SSA and factors such as ages, sex of patients or the other laboratory parameters, such as serum albumin, triglyceride, cholesterol, hemoglobin and serum iron levels. Patients treated with prednisolone, especially ones with RA, showed an increase of plasma SSA. It appears that Ge-132 promotes prednisolone effects. Our results indicate that a decrease in plasma SSA is not disease specific, but inversely correlates with the severity and activity of inflammation. The methodology to measure plasma SSA presented in this work provides a helpful tool for determining the actual activity of the diseases as well asin vivo studies of antiinflammatory agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Barbior BM. Oxygen-dependent microbial killing by phagocytes. N Eng J Med 1978; 298: 659–68.

    Google Scholar 

  2. Rister M, Bauermeister K. Superoxide-dismutase and superoxide-radical release in juvenile rheumatoid arthritis. Klin Wschr 1982; 60: 561.

    PubMed  Google Scholar 

  3. Singu M, Todoroki T, Nobunaga M. Generation of superoxide by immunologically stimulated normal human neutrophils and possible modulation by intracellular and extracellular SOD, and rheumatoid factors. Inflammation 1987; 11: 143–51.

    PubMed  Google Scholar 

  4. Prónai L, Ichikawa Y, Ichimori K, Nakazawa H, Arimori S. Association of enhanced superoxide generation by neutrophils with low superoxide scavenging activity of the peripheral blood, joint fluid, and their leukocyte components in rheumatoid arthritis: effects of slow-acting anti-rheumatic drugs. Clin Exp Rheumatol 1990 (in press).

  5. Shingu M, Nobunaga T. Serum factors from patients with systemic lupus erythematosus enhancing superoxide generation by normal neutrophils. J Invest Dermatol 1983; 81: 212–6.

    PubMed  Google Scholar 

  6. Michelson AM. Oxygen radicals. Agents Act 1982; 11 (Suppl): 179–83.

    Google Scholar 

  7. Sawyer DW, Donowitz GR, Mandell GL. Polymor-phonuclear neutrophils: effective antimicrobial force. Rew Infect Dis 1989; 11: S1532–44.

    Google Scholar 

  8. Halliwell B, Gutteridge JMC. The antioxidants of human extracellular fluids. Arch Biochem Biophys 1990; 280: 1–8.

    PubMed  Google Scholar 

  9. Yoshikawa T, Miyagawa H, Tanigawa T, Naito Y, Takemura T Itani K, Sugino S, Kondo M. Determination of superoxide activity using electron spin resonance. In: Hayaishi O, Niki E, Kondo M, Yoshikawa T, eds. Medical biochemical and chemical aspects of free radicals. Amsterdam: Elsevier Sci Publ, 1989: 809–12.

    Google Scholar 

  10. Brutkiewicz RR, Suzuki F. Biological activities and antitumor mechanism of an immunopotentiating organogermanium compound, Ge-132 (Review). In Vivo 1987; 189–203.

  11. Prónai L, Arimori S. Protective effect of carboxyethylgermanium sesquioxide (Ge-132) on superoxide generation by60Co-irradiated leukocytes. Biotherapy 1991; 3: 273–9.

    PubMed  Google Scholar 

  12. The American Rheumatism Association 1987. Revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315–24.

    Google Scholar 

  13. Steinbrocker O, Traeger CH, Batterman RC. Therapeutic criteria in rheumatoid arthritis. JAMA 1949; 140: 659–62.

    Google Scholar 

  14. The revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271.

  15. Bohan et al. A computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine 1977; 56: 225–30.

    PubMed  Google Scholar 

  16. LeRoy EC. Scleroderma (systemic sclerosis). In: Kelley WB, Harris ED, Ruddy S, Sledge CB, eds. Textbook of rheumatology. Philadelphia: W.B. Saunders, 1985: 1183–2005.

    Google Scholar 

  17. Engel AG. Myasthemia gravis and myasthenic syndromes. Ann Neurol 1984; 16: 519–28.

    PubMed  Google Scholar 

  18. Braunwald E, Isselbacher KJ, Petersdorf RG, Wilson JD, Martin JB, Fauci AS. Harrison's principle of internal medicine. 11th ed. New York: McGraw-Hill, 1987: 1743–7.

    Google Scholar 

  19. Prónai L, Arimori S, Nakazawa H. Superoxide scavenging activity of BG-104 before and after sonication — determined by ESR spin trapping method. Biotherapy 1990; 2: 63–8.

    PubMed  Google Scholar 

  20. Lowry OH, Rosenbrough NJ, Farr AL, Ranadall BJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265–75.

    PubMed  Google Scholar 

  21. Umeki S, Sumi M, Niki Y, Soejima R. Concentrations of superoxide dismutase and superoxide anion in blood of patients with respiratory infections and compromised immune systems. Clin Chem 1987; 33: 2230–3.

    PubMed  Google Scholar 

  22. Nakamura K, Endo H, Kashiwazaki S. Serum oxidation activities and rheumatoid arthritis. Int J Tiss Reac 1987; 9: 307–16.

    Google Scholar 

  23. Arimori S, Watanabe K, Yoshida M, Nagao T. Effect of Ge-132 as immunomodulator. In: Yamamura Y, Kotani S, Azura I, Koda A, Shiba T, eds. Immunomodulation by microbial products and related synthetic compounds. Amsterdam: Elsevier Sci. Publ., 1981: 498–500.

    Google Scholar 

  24. Arimori S, Yoshida M, Ichimura K. Improved rheumatoid arthritis case with Ge-132 administration evaluated by clinically and immunologically using two colour flow cytometry. Jpn J Clin Immunol 1990; 13: 80–6, in Japanese.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Prónai, L., Arimori, S. Decreased plasma superoxide scavenging activity in immunological disorders — carboxyethylgermanium sesquioxide (Ge-132) as a promoter of prednisolone. Biotherapy 4, 1–8 (1992). https://doi.org/10.1007/BF02171703

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02171703

Key words

Navigation