Mercurius solubilis: actions on macrophages
Received26 January 2010
revised22 January 2011
accepted11 May 2011
30 December 2017 (online)
Background: Macrophages play central roles in homeostasis as well as host defence in innate and acquired immunity, auto-immunity and immunopathology. Our research group has demonstrated the effects of highly diluted toxic substances in macrophages.
Aim: To investigate if highly diluted Mercurius solubilis (Merc sol), can activate or modulate macrophage functions.
Methods: We evaluated the effects of Merc sol in the 6, 12, 30 and 200 centesimal high dilutions (CH) potencies on mice peritoneal macrophages (in vitro and in vivo). Merc sol was added to mice’s drinking water for 7 days (in vivo treatment) and animals were euthanised and cells were collected. In vitro treatment was performed on macrophages and bone-marrow cell cultures.
Results: Macrophages showed activated morphology, both when Merc sol was added directly to the cell culture and to drinking water. The in vitro experiments showed enhanced morphological activation, increased interferon (IFN)γ release in the supernatant at lower dilutions and interleukin (IL)-4 production at higher dilutions. Increase in nitric oxide and decrease in superoxide (O2 −) and hydrogen peroxide (H2O2) were also observed. In vivo treatment caused a decrease in O2 − and increase in H2O2 production by macrophages.
Discussion: Taken together, the results allow us to conclude that highly diluted Merc sol modulates reactive oxygen species (ROS), reactive nitrogen species (RNS) and cytokine secretion, which are central mediators of the immune system, wound healing and body homeostasis.
- 1 Gordon S. The role of the macrophage in immune regulation. Res Immunol 1998; 149: 685-688.
- 2 Forman H.J., Torres M. Redox signaling in macrophages. Mol Aspects Med 2001; 22: 189-216.
- 3 Tegnér J., Nilsson R., Bajic V.B., Björkegren J., Ravasi T. Systems biology of innate immunity. Cell Immunol 2006; 244 (02) 105-109.
- 4 Bowdish D.M.E., Loffredo M.S., Mukhopadhyay S., Mantovani A., Gordon S. Macrophage receptors implicated in the "adaptive" form of innate immunity. Microbes Infect 2007; 9: 10.1016/j.micinf.2007.09.002.
- 5 Piemonte M.R., Buchi D.F. Analysis of IL-2, IFNγ and TNF-α production, α5β1 integrins and actin filaments distribution in intraperitoneal mouse macrophages treated with homeopathic medicament. J Submicrosc Cytol Pathol 2002; 3: 255-263.
- 6 Lopes L., Godoy L.M.F., Oliveira C.C., Gabardo J., Schadeck R.J.G., Buchi D.F. Phagocytosis, endosomal/lisosomal system and other cellular aspects of macrophage activation by Canova medication. Mícron 2006; 37: 277-287.
- 7 Oliveira C.C., Oliveira S.M., Godoy L.M.F., Gabardo J., Buchi D.F. Canova, a Brazilian medical formulation, alters oxidative metabolism of mice macrophages. J Infect 2006; 52: 420-432.
- 8 Oliveira C.C., Oliveira S.M., Goes V.M., Probst C.M., Krieger M.A., Buchi D.F. Gene expression profiling of macrophages following mice treatment with an immunomodulator medication. J Cell Biochem 2008; 104: 1364-1377.
- 9 Abud A.R., Cesar B., Cavazzani L.M., Oliveira C.C., Gabardo J., Buchi D.F. Activation of bone marrow cells treated with Canova in vitro. Cell Biol Int 2006; 30: 808-816.
- 10 Cesar B., Abud A.R., Oliveira C.C. et al. Activation of mononuclear bone marrow cells treated in vitro with a complex homeopathic medication. Micron 2008; 39 (04) 461-470.
- 11 Cesar B., Abud A.R., de Oliveira C.C. et al. Treatment with at homeopathic complex medication modulates mononuclear bone marrow cell differentiation. eCAM 2011; 2011: 212459.
- 12 Guimarães F.S.F., Abud A.P.R., Oliveira S.M. et al. Stimulation of lymphocyte anti-melanoma activity by co-cultured macrophages activated by complex homeopathic medication. BMC Cancer 2009; 9: 293 http://www.biomedcentral.com/1471-2407/9/293.
- 13 Aronson J.K. Mercury and Mercurial Salt. Meyler’s Side Effects of Drugs. The International Encyclopedia of Adverse Drug Reactions and Interactions. 5th edn 2006. Elsevier; 2260-2266.
- 14 Ribeiro Filho A. Novo Repertório de Sintomas Homeopáticos. São Paulo: Robe 1996: 1201.
- 15 Buchi D.F., de Souza W. Internalization of surface components during ingestion of Saccharomyces cerevisiae by macrophage. J Submicrosc Cytol Pathol 1992; 24 (01) 135-141.
- 16 Green L.C., Wagner D.A., Glogowski J., Skipper P.L., Wishnok J.S. Analysis of nitrate, nitrite, and (15N)-nitrate in biological fluids. Anal Biochem 1982; 126: 131-138.
- 17 Johnston R.B., Godzik C.A., Cohn Z.A. Increased superoxide anion production by immunologically activated and chemically elicited macrophages. J Exp Med 1978; 148: 115-127.
- 18 Pick E., Mizel D. Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J Immunol Methods 1981; 46: 211-226.
- 19 Segal A.W., Abo A. The biochemical basis of the NADPH oxidase of phagocytes. TIBS 1993; 18: 43-47.
- 20 Yoshimura A., Hanada T. Regulation of cytokine signaling and inflammation. Cytokine Growth Factor Rev 2002; 13: 413-421.
- 21 Mosmann T.R., Coffman R.L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989; 7: 145-173.
- 22 Kim S.H., Johnson V.J., Sharma R.P. Mercury inhibits nitric oxide production but activates proinflammatory cytokine expression in murine macrophage: differential modulation of NF-κB and p38 MAPK signaling pathways. Nitric Oxide 2002; 7: 67-74.
- 23 Johansson U., Sander B., Hultman P. Effects of the murine genotype on T cell activation and cytokine production in murine mercury-induced autoimmunity. J Autoimmun 1997; 10: 347-355.
- 24 Cristea A., Nicula S., Dare V. Pharmacodynamic effects of very high dilutions of Belladonna on the isolated rat duodenum. In: Bastide M. (ed). Signals Images. 1997. Dordrecht: Kluwer Academic Publishers; 161-170.
- 25 Pedalino C.M.V., Perazzo F.F., Carvalho J.C.T., Martinho K.S., Massoco C., Bonamim L.V. Effect of Atropa belladonna and Echinacea angustifolia in homeopathic dilution on experimental peritonitis. Homeopathy 2004; 93: 193-198.
- 26 Bruckdorf R. The basics about nitric oxide. Mol Aspects Med 2005; 26: 3-31.
- 27 Coleman J.W. Nitric oxide in immunity and inflammation. Int Immunopharmacol 2001; 1: 1397-1406.
- 28 Nathan C., Shiloh M.U. Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. PNAS 2000; 97 (16) 8841-8848.
- 29 Zhou Y., Lin G., Murtaugh M.P. Interleukin-4 suppresses the expression of macrophage NADPH oxidase heavy chain subunit (gp91-phox). Biochimica et Biophysica Acta 1995; 1265: 40-48.
- 30 Cross A.R., Segal A.W. The NADPH oxidase of professional phagocytes-prototype of the NOX electron transport chain systems. Biochimica et Biophysica Acta 2004; 1657: 1-22.
- 31 Brown D.I., Griendling K.K. Nox proteins in signal transduction. Free Radic Biol Med 2009; 47: 1239-1253 10.1016/j.freeradbiomed.2009.07.023.
- 32 Veal E.A., Day A.M., Morgan B.A. Hydrogen peroxide sensing and signaling. Mol Cell 2007; 26: 1-14.