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Zinc monoglycerolate: A slow-release source of zinc with anti-arthritic activity in rats

  • Inflammation and Immunomodulation
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Abstract

Zinc repletion by parental administration of zinc monoglycerolate (ZMG) or certain other lipophilic zinc complexes, suppressed the development of adjuvant-induced polyarthritis in rats.

While ZMG was effective when given parenterally over various limited time schedules (immunosuppressant, therapeutic, singledose), it was not effective given orally. The complex showed no acute anti-inflammatory activity in the carrageenan paw oedema assay and little gastric-intestinal or other organ toxicity. When injected s.c. it caused very much less local irritation than most zinc salts.

Being lubrous, ZMG could be applied as the dry powder for rubbing into the skin and by this route was found to have anti-arthritic activity.65Zn was shown to be absorbed and excreted in the faeces (biliary exretion) after applying65Zn-ZMG dermally to shaved dorsal skin of rats.

ZMG showed consistent anti-arthritic activity in rats under conditions in which 2 gold drugs (aurothiomalate, Auranofin) exhibited variable effects, depending on the strain of rat. The role of zinc and its availability in chronic inflammation are discussed on the basis of these studies.

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References

  1. W. Schmollack, L. T. Phuoc and H. Bekemeier,The influence of phenylbutazone on the zinc level in serum and paw tissue of rats with adjuvant arthritis. Agents and Actions Supp.10, 83–97 (1982).

    PubMed  Google Scholar 

  2. R. Milanino, A. Cassini, A. Conforti, L. Franco, M. Marella, U. Moretti and G. P. Velo,Copper and zinc status during acute inflammation. Agents and Actions19, 215–223 (1984).

    Google Scholar 

  3. J. Neve, J. Fontaine, A. Peretz and J. P. Famaey,Changes in zinc, copper and selenium status during adjuvant-induced arthritis in rats. Agents and Actions25, 146–155 (1988).

    PubMed  Google Scholar 

  4. S. P. Pandey, S. K. Bhattacharya and S. Sundar,Zinc in rheumatoid arthritis. Ind. J. Med. Res.81, 618–620 (1985).

    Google Scholar 

  5. J. J. Oppenheim, K. Matsushima, T. Yoshimura, E. J. Leonard and R. Neta,Relationship between interleukin-1, tumor necrosis factor and a neutrophil attracting peptide. Agents and Actions26, 134–140 (1989).

    PubMed  Google Scholar 

  6. T. Fukushima, Y. Lijima and F. Kosaka;Endotoxin-induced zinc accumulation by liver cells is mediated by metallothionein synthesis. Biochem. Biophys. Res. comm.152, 874–878 (1988).

    PubMed  Google Scholar 

  7. W. A. Briggs, M. M. Pedersen, S. K. Mahajan, D. H. Sillix, A. S. Prasad and F. D. McDonald,Lymphocyte and granulocyte function in zinc-treated and zinc deficient hemodialysis patients, Kidney Intl.21, 827–839 (1982).

    Google Scholar 

  8. A. Prasad,Effect of trace metal imbalance in human diseases. Acta Pharmacol. Toxicol.59, Suppl. 7, 94–103 (1986).

    Google Scholar 

  9. Y. Huo, J. Ekholm and D. J. Hanahan,A preferential inhibition by Zn (II) on PAF- and thrombin-induced serotonin secretion from washed rabbit platelets. Arch. Biochem. Biophys.260, 841–846 (1988).

    PubMed  Google Scholar 

  10. R. L. Willson,Vitamin, selenium, zinc and copper interactions in free-radical protection against ill-placed iron. Proc. Nutr. Soc.46, 27–34 (1987).

    PubMed  Google Scholar 

  11. J. Yatuyanagi, K. Iwai and T. Ogiso,Suppressive effects of zinc on some functions of neutrophils. Studies with carrageenan-induced inflammation in rats. Chem. Pharm. Bull.35, 699–704 (1987).

    PubMed  Google Scholar 

  12. P. J. Fraker, M. E. Gershwin, R. A. Good and A. Prasad,Interrelationships between zinc and immune function. Fed. Proc.45, 1474–1479 (1986).

    PubMed  Google Scholar 

  13. C. L. Reardon and D. D. Lucas,Heavy-metal mitogenesis: Zn (II) and Hg (II) induce cellular cytotoxicity and interfer-on protections in murine T lymphocytes. Immunobiol.175, 455–449 (1987).

    Google Scholar 

  14. M. W. Whitehouse, R. M. Taylor, I. R. Garrett and B. Vernon-Roberts,Zinc monoglycerolate: anti-arthritic slowly released source of zinc. 2nd World Conf. Inflammation (Monte Carlo), A219 (1986).

  15. M. W. Whitehouse, R. M. Taylor, D. P. Fairlie, I. R. Garrett and B. Vernon-Roberts,Zinc monoglycerolate: a slow release source of therapeutic zinc. Clin. Exp Pharmacol. Physiol. Suppl.11, 117 (1987).

    Google Scholar 

  16. E. W. Radoslovich, M. Raupach, P. G. Slade and R. M. Taylor,Crystalline cobalt, zinc, manganese and iron alkoxides of glycerol. Austr. J. Chem.23, 1963–1971 (1970).

    Google Scholar 

  17. M. W. Whitehouse,Rat polyarthritis: induction with adjuvants constituted with mycobacteria (and oils) from the environment, J. Rheumatol.9, 494–501 (1982).

    PubMed  Google Scholar 

  18. Y-H. Chang, C. M. Pearson and C. Abe,Adjuvant polyarthritis IV. Induction by synthetic adjuvant. Immunologic, histopathological and other studies. Arthritis Rheum.23, 62–71 (1980).

    PubMed  Google Scholar 

  19. K. D. Rainsford and M. W. Whitehouse,Anti-ulcer activity of zinc monoglycerolate (Glyzinc ®):a slow-release zinc formulation. Clin. Exp. Physiol. Pharmacol.12 (Suppl.) 119 (1988).

    Google Scholar 

  20. D. P. Fairlie, M. W. Whitehouse and R. M. Taylor,Zinc monoglycerolate — a slow-release source of zinc and glycerol. Solubilization by bioconstituent ligands (submitted for publication).

  21. P. A. Simkin,Oral zinc sulphate in rheumatoid arthritis. Lancetii, 539–542 (1976).

    Google Scholar 

  22. M. A. Cimmino, A. Mazzucotelli, G. Rovetta, G. Bianchi and M. Cutolo,The controversy over zinc sulphate efficacy in rheumatoid and psoriatic arthritis. Scand. J. Rheumatol.13, 191–192 (1984).

    PubMed  Google Scholar 

  23. K. Svenson, R. Hallgren, E. Johansson and U. Lindh,Abnormal calcium, magnesium and zinc stores in peripheral blood cells from patients with inflammatory connective tissue disease. Acta Pharmac. Toxicol.59, Suppl. 7, 386–391 (1986).

    Google Scholar 

  24. K. L. G. Svenson, R. Hallgren, E. Johansson and U. Lindh,Reduced zinc in peripheral blood cells from patients with inflammatory connective tissue diseases. Inflammation9, 189–199 (1985).

    PubMed  Google Scholar 

  25. R. Hallgren, N. Feltelius and U. Lindh,Redistribution of minerals and trace elements in chronic inflammation — a study on isolated blood cells from patients with ankylosing spondylitis. J. Rheumatol.14, 548–553 (1987).

    PubMed  Google Scholar 

  26. C. A. Pasternak,A novel form of host defence: membrane protection by Ca 2+ and Zn2+. Bioscience Rep7, 81–91 (1987).

    Google Scholar 

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Author notes

  1. K. D. Rainsford

    Present address: Faculty of Health Sciences, McMaster University, L8N3Z5, Hamilton, Ontario, Canada

Authors and Affiliations

  1. Department of Pathology, University of Adelaide, G.P.O. Box 498, 5001, South Australia

    M. W. Whitehouse & B. Vernon-Roberts

  2. Department of Pharmacology, University of Cambridge, CB2 2QD, UK

    K. D. Rainsford

  3. Divisions of Soils, CSIRO, 5064, Urrbrae, South Australia

    R. M. Taylor

Authors
  1. M. W. Whitehouse
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  2. K. D. Rainsford
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  3. R. M. Taylor
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  4. B. Vernon-Roberts
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Whitehouse, M.W., Rainsford, K.D., Taylor, R.M. et al. Zinc monoglycerolate: A slow-release source of zinc with anti-arthritic activity in rats. Agents and Actions 31, 47–58 (1990). https://doi.org/10.1007/BF02003221

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  • DOI: https://doi.org/10.1007/BF02003221

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