Skip to main content
Log in

Differences in the effects of the antirheumatic drugs, bucillamine andd-penicillamine, on mitogen-induced proliferation of mouse spleen cells

  • Inflammation and Immunomodulation
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

The effect of bucillamine [N-(2-mercapto-2-methylpropionyl)-l-cysteine] a new antirheumatic drug, on the concanavalin A (Con A)-induced proliferation of mouse spleen cells was compared with the effect ofd-penicillamine (d-pen). Bucillamine inhibited the Con A-induced incorporation of thymidine (TdR) into mouse spleen cells in a dose-dependent fashion. At the concentration of 10−4 M, bucillamine inhibited the incorporation by approximately 80%. The inhibitory effect of bucillamine was not enhanced by the addition of copper. In contrast,d-pen showed the same degree of inhibition only in the presence of copper. (4R)-7,7-Dimethyl-6-oxo-tetrahydro-3H-1,2,5-dithiazepine-4-carboxylic acid (SA981), an intramolecular disulfide derivative of bucillamine, also showed the same degree of inhibition as bucillamine in the absence and presence of copper, whereasd-penicillamine disulfide did not show the inhibitory effect even in the presence of copper. The inhibitory effects of bucillamine and SA981 were not abolished significantly by the addition of catalase which restored the inhibition byd-pen plus copper. The mechanism of inhibition byd-pen plus copper is believed to involve the production of hydrogen peroxide resulting from the oxidation ofd-pen. The results in this study, however, indicated that the inhibitory effect of bucillamine is not due to the production of hydrogen peroxide.

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. C. Abe,Clinical evaluation of immunomodulators. Int. J. Immunother.1, 7–10 (1985).

    Google Scholar 

  2. S. Kashiwazaki and Y. Shiokawa,Bucillamine: A new immunomodulator. Int. J. Immunother.3, 1–6 (1987).

    Google Scholar 

  3. H. Fujimura, Y. Hiramatsu, Y. Tamura, M. Yanagihara, A. Koda, H. Nagai, K. Uda, T. Iso and H. Yamauchi,Pharmacological studies of new sulfyhdryl compounds 2-mercapto-2-methyl-propanoyl-L-cysteine. Folia Pharmacol. Japon.76, 117–129 (1980).

    Google Scholar 

  4. S. Kosaka, K. Itoh and K. Kumagai,An in-vitro study of SA-96 (DE-019), an immunomodulator, and its application in the treatment of rheumatoid arthritis.Tohoku J. Med. 96, 13–21 (1983).

    Google Scholar 

  5. M. Hayashi, C. Abe, H. Yamauchi, T. Iso and Y. Shiokawa,Effects of SA96 on self-defence system in Balb/c mice. Int. J. Immunother.1, 219–225 (1985).

    Google Scholar 

  6. M. Hayashi, C. Abe, R. T. Nozawa, T. Yokota, T. Iso and Y. Shiokawa,Effects of immunomodulators on candidacidal activity of normal peritoneal cells in BALB/c mice. Int. J. Immunopharmac.8, 299–304 (1986).

    Article  Google Scholar 

  7. H. Yamauchi, K. Morikawa, M. Kuwano, M. Hikida, K. Fujimura, M. Horiuchi, O. Uemura and T. Iso,Pharmacological studies of N-(2-mercapto-2-methylpropionyl)-L-cysteine (SA96). Folia Pharmacol. Japon.86, 25–33 (1985).

    Google Scholar 

  8. K. Ishikawa and M. Sakaguchi,SA96 (N-(2-mercapto-2-methylpropanoyl)-L-cysteine) in rheumatoid arthritis. Scand. J. Rheumatol.15, 85–90 (1986).

    PubMed  Google Scholar 

  9. H. V. Aposhian,Biochemical and pharmacological properties of the metal-binding agent penicillamine. Fed. Proc.20, 185–190 (1961).

    Google Scholar 

  10. J. M. Walshe,Penicillamine, a new oral therapy for Wilson's disease. Am. J. Med.21, 487–495 (1956).

    Article  PubMed  Google Scholar 

  11. G. Starkebaum and R. K. Root,D-Penicillamine: Analysis of the mechanism of copper-catalyzed hydrogen peroxide generation. J. Immunol.134, 3371–3378 (1985).

    PubMed  Google Scholar 

  12. P. E. Lipsky and M. Ziff,The effect of D-Penicillamine on mitogen-induced human lymphocyte proliferation: Synergistic inhibition oby D-Penicillamine and copper salts. J. Immunol.120, 1006–1013 (1978).

    PubMed  Google Scholar 

  13. P. E. Lipsky and M. Ziff,Inhibition of human helper T cell function in vitro by D-Penicillamine and CuSO 4. J. Clin. Invest.65, 1069–1076 (1980).

    PubMed  Google Scholar 

  14. P. E. Lipsky,Immunosuppression by d-Penicillamine in vitro. J. Clin. Invest.73, 53–65 (1984).

    PubMed  Google Scholar 

  15. Y. Takagi, M. Shikita, T. Terasima and S. Akaboshi,Specificity of radioprotective and cytotoxic effects of cysteamine in HeLa S 3 cells: Generation of peroxide as the mechanism of paradoxical toxicity. Radiat. Res.60, 292–301 (1974).

    PubMed  Google Scholar 

  16. H. P. Misra,Generation of superoxide free radical during the autooxidation of thiols. J. Biol. Chem.249, 2151–2155 (1973).

    Google Scholar 

  17. S. Sugawara, M. Ishigami and T. Kageyama,Phase I study of N-(2-mercapto-2-methylpropionyl)-l-cysteine (SA96). (I) Single administration study. Rinsyo Yakuri16 611–620 (1985).

    Google Scholar 

  18. S. Sugawara, M. Ishigami and T. Kageyama,Phase I study of N-(2-mercapto-2-methylpropionyl)-l-cysteine (SA96). (II) Continuous 6-day administration study. Rinsyo Yakuri16, 621–630 (1985).

    Google Scholar 

  19. N. Morikawa, J. Matsumoto, H. Kito and T. Iso,Metabolic fate of N-(2-mercapto-2-methylpropionyl)-L-cysteine (SA96) (II). Absorption, distribution, metabolism and excretion during repeated administrations to male rats. Iyakuhin Kenkyu16, 808–817 (1985).

    Google Scholar 

  20. V. A. Ruiz-Torres, Zur Pharmakokinetik und zum Stoffwechsel vonD- andL-Penicillamin. II. Mitteilung: Verteilung vonD- andL-Penicillamin-14C im Organismus der Ratte nach peroraler Verabfolgung. Arzneim.-Forsch.24, 1043–1046 (1974).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mita, S., Matsunaga, K. Differences in the effects of the antirheumatic drugs, bucillamine andd-penicillamine, on mitogen-induced proliferation of mouse spleen cells. Agents and Actions 30, 363–368 (1990). https://doi.org/10.1007/BF01966300

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01966300

Keywords

Navigation