Skip to main content
Log in

Effects of supplementation with higher levels of manganese and magnesium on immune function

  • Article
  • Drug Development
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

The magnesium (Mg) and manganese (Mn) were evaluated for its effectiveness as an immunomodulator in rats. The treatments were as follows: Group 1, AIN-93M diet (0.05% Mg, 0.001% Mn); Group 2, high-dose Mg (0.1% Mg, 0.001% Mn); and Group 3, high dose Mn (0.05% Mg, 0.01% Mn) (n-12/group). After 12 weeks of supplementation, rats were sacrificed to assess the effect on a range of innate responses (tumoricidal activity, oxidative burst and nitric oxide) and the mitogen-stimulated lymphoproliferative response. Immune function was significantly affected in both the high dose Mg and the Mn group. Lymphocyte proliferative responses and NK cell activity were measured in pooled spleen from each group. The mitogen response of lymphocytes to LPS in the spleen was significantly reduced in high dose Mg-treated groups, whereas the response to ConA was not affected in both high dose minerals-treated groups. The reactive oxygen species level of macrophages was decreased in both groups. These effects were more pronounced in high dose Mg-treated group. Nitric oxide production was also decreased in high dose minerals-treated group. In addition, tumoricidal activities of splenic NK cell and peritoneal macrophage in mineral exposed rats were significantly increased. Moreover, percent death of macrophage was reduced in two groups receiving high dose mineral supplements. Taken together, the present data suggest that high dose trace min-erals exert a differential effect on the function of immune cells.

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

  • Adams, D. O. and Hamilton, T. A., The cell biology of macrophage activation.Annu. Rev. Immunol., 2, 283–318 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Arenzana-Seisdedos, F. and Virelizier J., Interferons as macrophage activating factors. II. Enhanced secretion of interleukin 1 by lipopolysaccharide-stimulated human moncytes.Eur. J. Immunol., 13, 437–440 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Bannister, J. V., Bannister, W. H., and Rotillo, G., Aspects of the structure, function, and applications of Superoxide dismutase.CRC Crit. Rev. Biochem., 22, 111–118 (1987)

    Article  PubMed  CAS  Google Scholar 

  • Chandra, R. K., Nutrition and the immune system: an introduction.Am. J. Clin. Nutr., 66, 460S-463S (1997).

    PubMed  CAS  Google Scholar 

  • Choriki, M., Freudenberg, M., Calanos, C., Poindron, P., and Bartholeyns, J., Antitumoral effects of lipopolisacchride, tumor necrosis factor, interferon and activated macrophages: synergism and tissue distribution.Anticancer Res., 9, 1185–1190 (1989).

    Google Scholar 

  • Dekker, J. P. and van Gorkum, H. J., Electron transfer in the water-oxidizing complex of photosystem II.J. Bioenerg. Biomembr., 19, 125–142 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Denlinger, L. C., Fisette, P. L., Garis, K. A., Kwon, G., Vazquez-Torres, A., Simon, A. D., Nguyen, B., Proctor, R. A., Bertics, P. J., and Corbett, J. A., Regulation of inducible nitric oxide synthase expression by macrophage purinoreceptors and calcium.J. Biol. Chem., 271, 337–42 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Durlach, J., Magnesium in Clinical Practice. Libbey, London, (1988).

    Google Scholar 

  • Frausto da Silva, J. J. R. and Williams, R. J. P., The Biological Chemistry of the Elements. Oxford, New York (1991).

    Google Scholar 

  • Galland, L., Magnesium and immune function: an overview.,Magnesium 7, 290–299 (1988).

    PubMed  CAS  Google Scholar 

  • Garrison, R. H. and Somer, E., Minerals. Keates, New Canaan, (1985).

    Google Scholar 

  • Ghosh, A. and Greenberg, M. E., Calcium signaling in neurons: Molecular mechanisms and cellular consequences.Science, 268, 239–247 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Gincel, D., Zaid, H., and Shoshan-Barmatz, V., Calcium binding and translocation by the voltage-dependent anion channel: a possible regulatory mechanism in mitochondrial function.Biochem. J., 358(Pt 1), 147–155 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Halestrap, A. P., McStay, G. P., and Clarke, S. J., The permeability transition pore complex: another view.Biochimie., 84(2–3), 153–166 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Hsu, A., Regulation of nuclear calcium uptake by inositol phosphates and external calcium.Biochem. Biophs. Res. Commun., 243, 653–656 (1998).

    Article  CAS  Google Scholar 

  • Keller, R., Keist, R., and Frei, K., Lymphokines and bacteria that induce tumoricidal activity, trigger a different secretory response in macrophages.Eur. J. Immunol., 20, 695–698 (1990).

    Article  PubMed  CAS  Google Scholar 

  • Leach, R. M., Role of manganese in the synthesis of mucopolysaccharides.Fed., Proc., 26, 118–120 (1969).

    Google Scholar 

  • Larsen, C. J., The BCL2 gene is the prototype of a gene family that controls programmed cell death (apoptosis).Annales Genet., 37, 121–134 (1994).

    CAS  Google Scholar 

  • Mazur, A., Maie, J. A., Rock, E., Gueux, E., Nowacki, W., and Rayssiguier, Y., Magnesium and the inflammatory response: Potential physiopathological implications.Arch. Biochem. Biophys., 458(1), 48–56 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Meiri, U. and Rahamimoff, R., Neuromuscular transmission: inhibition by manganese ions,Science, 176, 308–309 (1972)

    Article  PubMed  CAS  Google Scholar 

  • Mishra, O. P., Qayyum, I., and Delivoria-papadopoulos, M., Hypoxia-induced modification of the inositol triphosphate (IP3) receptor in neuronal nuclei of newborn piglets: The role of nitric oxide.J. Neurosci. Res., 74, 333–338 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Mosmann, T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.J. Immunol. Meth., 65, 55–63 (1983).

    Article  CAS  Google Scholar 

  • Nicotera, P. and Rossi, A. D., Nuclear Ca: Physiologic regulation and role in apoptosis.Mol. Cell. Biochem., 135, 89–98 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Rivadeneira, D. E., Grobmyer, S. R., Naama, H.A., Mackrell, P. J., Mestre, J. R., Stapleton, P. P., and Daly, J. M., Malnutrition-induced macrophage apoptosis.Surgery, 129, 617–625 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Pryor, W. A., Houk, K. N., Foote, C. S., Fukuto, J. M., Ignarro, L. J., Squadrito, G. L., and Davies, K. J., Free radical biology and medicine: it’s a gas, man!.Am. J. Physiol. Regul. Integr. Comp. Physiol., 291, R491–511 (2006).

    PubMed  CAS  Google Scholar 

  • Singh, R. K., Kooreman, K. M., Babbs, C. F., Fessier, J. F., and Salaris, S. C., Potential use of simple manganese salts as antioxidant drugs in horses.Am. J. Vet. Res., 53 (10), 1822–1829 (1992).

    PubMed  CAS  Google Scholar 

  • Soares, A. M., Oshima-Franco, Y., Vieira, C. A., Leite, G. B., Fletcher, J. E., Jiang, M. S., Cintra, A. C., Giglio, J. R., and Rodrigues-Simioni, L., Mn2+ ions reduce the enzymatic and pharmacological activities of bothropstoxin-l, a myotoxic Lys49 phospholipase A(2) homologue from Bothrops jararac- ussu snake venom.Int. J. Biochem. Cell. Biol., 34, 668–677 (2002)

    Article  PubMed  CAS  Google Scholar 

  • Son, E. H., Moon, E. Y., Rhee, D. K., and Pyo, S., Stimulation of various functions in murine peritoneal macrophages by high mannuronic acid-containing alginate (HMA) exposure in vivo.Int. Immunopharmacol., 1, 147–154 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Strijdom, H., Muller, C., and Lochner, A., Direct intracellular nitric oxide detection in isolated adult cardiomyocytes: flow cytometric analysis using the fluorescent probe, diaminofluorescein.J. Mol. Cell Cardiol., 37 (4), 897–902 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Stuehr, D. J., and Marietta, M.A., Synthesis of nitrite and nitrate in macrophage cell lines.Cancer. Res., 47, 5590–5594 (1987).

    PubMed  CAS  Google Scholar 

  • Trinchieri, G., Biology of natural killer cells.Adv. Immunol., 47, 187–376 (1989).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Suhkneung Pyo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Son, EW., Lee, SR., Choi, HS. et al. Effects of supplementation with higher levels of manganese and magnesium on immune function. Arch Pharm Res 30, 743–749 (2007). https://doi.org/10.1007/BF02977637

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02977637

Key words

Navigation