ADVERSE EFFECTS OF METALS ON THE GUT FLORA

  • Volatile derivatives from metals such as mercury, arsenic, bismuth, tellurium ect... can exert their toxic effects on human health not only by direct interaction with host cells but also by disturbing the physiological gut microflora.

Meyer J, Michalke K, Kouril T, Hensel R. Votalisations of metals and metalloids: an inherent feature of methanoarchea ? Syst Applied Microbiol. 2008, June; 31(2):81-7. Epub 2008 April 18.

  • Oral lead exposure induces dysbacteriosis in rats: For the first time it was shown that oral lead exposure causes drastic changes in the gut microbial community. Proportional to the lead dose received, the relative number of lactose-negative E.coli cells increased dramatically (up to 1,000-fold) in comparison to the other microbial groups during 2 wk of exposure. Considering the number of microbes in the intestine, such a shift in intestinal microflora (dysbacteriosis) is very significant. Adhesion studies showed certain stimulating effects of lead on E. coli attachment to rat intestinal epithelium as compared to Lactobacillus attachment. This study may provide important clues for understanding the pathological effects of metal dietary toxins in human beings.

Sadykov R,Digel I,Artmann AT,Porst D,Linder P,Kayser P,Artmann G,Savitskaya I,Zhubanova A. Oral Lead Exposure Induces Dysbacteriosis in Rats. J Occup Health.2009;51(1):64-73. Epub 2008 Dec 19

  • "...cinnabar* induced disturbance in energy metabolism, amino acid metabolism and gut microflora environment as well as slight injury in liver and kidney, which might indirectly result from cinnabar* induced oxidative stress."

Wei L, Liao P, Wu H, Li X, Pei F, Li W, Wu Y. Toxicological effects of cinnabar in rats by NMR-based metabolic profiling of urine and serum. Toxicol Appl Pharmacol. 2008 Mar 15;227(3):417-29. Epub 2007 Nov 28.

* Cinnabar is the ore of mercury.

  • Mercury-containing dental amalgam is known to be a source of human exposure to mercury. We have explored the use of electron yield Hg L(III) X-ray absorption spectroscopy to characterize the chemical nature of dental amalgam surfaces. We find that the method is practical and that it shows extensive mercury depletion in the surface of the aged amalgam with significant differences between old and fresh amalgam surfaces. Whereas the fresh amalgam gives spectra that are typical of metallic mercury, the aged amalgam is predominantly beta-mercuric sulfide. The toxicological implications of these results are discussed.

George GN, Singh SP, Hoover J, Pickering IJ. The chemical forms of mercury in aged and fresh dental amalgam surfaces. Chem Res Toxicol. 2009 Nov;22(11):1761-4.

  • Mercuric sulfide (HgS) is a major component of cinnabar, which has been used as a sedative drug in China for more than 2000 years. Because its toxicological effects are still unclear, we attempted to verify the toxic effects of HgS,focused on liver and immune organs such as the spleen and thymus. Male ICR mice were administered HgS (0.02, 0.2, 2.0 g/kg/day) by gavage for 4 weeks. During the administration period, HgS-treated mice did not reveal overt signs of clinical toxicity. HgS had no significant effect on body weight, food consumption, water consumption, and organ weights. In spite of its known insolubility, HgS was absorbed by the gastrointestinal tract and accumulated in the liver, spleen and thymus in a dose-dependent manner. In the biochemical and histological examination, HgS did not cause hepatotoxicity. However, HgS significantly increased both CD8(+) T lymphocytes and CD4(+)CD8(+) lymphocyte populations in the spleen without changing in the thymus. In the histological evaluation, HgS induced enlargement with marked hyperplasia and increase of lymphoid follicles in the spleen. In addition, HgS induced the gene expression of pro-inflammatory cytokines in the spleen and thymus. Our results suggest that insoluble HgS was absorbed by the gastrointestinal tract, accumulated in the spleen and thymus, and thus could affect immune systems.

Son HY, Lee S, Park SB, Kim MS, Choi EJ, Singh TS, Bae Y, Kwack SJ, Kang TS, Shin HI, Baek MC, Kim SH. Toxic effects of mercuric sulfide on immune organs in mice. Immunopharmacol Immunotoxicol. 2010 Jun;32(2):277-83.

  • This study compared the neurobehavioral toxicities of three mercurial compounds: methyl mercury (MeHg) which is soluble and organic. and mercuric sulfide (HgS) and cinnabar (naturally occurring HgS), which are insoluble and inorganic. Cinnabar, a Chinese mineral medicine, is still used as a sedative in some Asian
    countries, but there is relatively little toxicological information about it. These mercurial compounds were administered intraperitoneally (MeHg, 2 mg/ kg) or orally (HgS and cinnabar, 1.0 g/kg) to male rats once every day for 13 consecutive days with assays conducted during or after discontinuous administration for 1 h, 2, 8 and 33 weeks. Neurotoxicity was assessed based on the active avoid-ance response and locomotor activity.
    The results obtained showed that MeHg and cinnabar prominently and irreversibly caused a decrease in body weight, prolongation of latency for escape from electric shock, a decrease in the percentage for the conditioned avoidance response (CAR) to electric shock, impairment of spontaneous locomotion and inhibition of Na+/K+-ATPase activity of the cerebral cortex. In contrast. HgS reversibly inhibited spontaneous locomotion and Na+/K+-ATPase activity. It was noted that HgS significantly decreased the latency of escape from electric shock during the ad-ministration period, which lasted for 33 weeks after discontinuous administration. In fact that pretreatment with arecoline (a cholinergic receptor agonist) but not fipexide (a dopaminergic receptor agonist) could significantly shorten the prolonged latency for escape caused by MeHg and cinnabar, suggested that the deficit in the active avoidance response was perhaps, at least in part, mediated by the dysfunction of the cholinergic rather than the dopaminergic system. Determination of the Hg levels of the whole blood and cerebral cortex revealed that the tissue mercury content was highly correlated with the degree of neurobehavioral toxicity of these Hg compounds. These findings suggest that insoluble HgS and cinnabar can be absorbed from the G-I tract and distributed to the brain. The possibility that contamination due to other minerals in the cinnabar is responsible for the greater neurotoxic effects compared to HgS is under investigation.

Chuu JJ, Liu SH, Lin-Shiau SY. Effects of methyl mercury, mercuric sulfide and cinnabar on active avoidance
responses, Na+/K+-ATPase activities and tissue mercury contents in rats. Proc Natl Sci Counc Repub China B. 2001 Apr;25(2):128-36.

  • Mercury,copper, Ag-Cu alloy, fluoride and zinc from dental amalgam showed antibacterial activity (Hg>Cu>F>Zn)

Morrier JJ at al. Antimicrobial activity of amalgams, alloys and their elements and phases. Dent Mater. 1998 Mar;14(2):150-7.

  • Candida Albicans and Tropicalis are more resistant to the toxic effects of mercury, cadmium, lead and arsenic than Saccharomyces Cerevisiae.

Berdicevsky I, Duek L, Merzbach D, Yannai S. Susceptibility of different yeast species to environmental toxic metals. Environ Pollut. 1993;80(1):41-4.

  • Mercury can be methylated by oral and intestinal bacteria.

Heintze U, Edwardsson S, Derand T, Birkhed D. Methylation of mercury from dental amalgam and mercuric chloride by oral streptococci in vitro. Scand J Dent Res. 1983 Apr;91(2):150-2.

Rowland IR, Grasso P, Davies MJ. The methylation of mercuric chloride by human intestinal bacteria. Experientia. 1975 Sep 15;31(9):1064-5.

  • The gastrointestinal uptake of mercury from dental amalgam is of quantitative importance during dental treatment.

Geijersstam E, Sandborgh-Englund G, Jonsson F, Ekstrand J. Mercury uptake and kinetics after ingestion of dental amalgam. J Dent Res. 2001 Sep;80(9):1793-6.

  • Mercury is absorbed through the gut lining.

Sandborgh-Englund G, Einarsson C, Sandstrom M, Ekstrand J. Gastrointestinal absorption of metallic mercury. Arch Environ Health. 2004 Sep;59(9):449-54.

  • Mercury released from dental "silver" fillings provokes an increase in mercury- and antibiotic-resistant bacteria in oral and intestinal floras of primates.

Summers AO et al. Mercury released from dental "silver" fillings provokes an increase in mercury- and antibiotic-resistant bacteria in oral and intestinal floras of primates. Antimicrob Agents Chemother. 1993 Apr;37(4):825-34.

  • Mercury,copper, cadmium, indium and zinc are released into the gastrointestinal tract from dental amalgam.
  • The release of mercury and copper was fifty times higher from high copper amalgam than from other amalgams.

Brune D, Gjerdet N, Paulsen G. Gastrointestinal and in vitro release of copper, cadmium, indium, mercury and zinc from conventional and copper-rich amalgams. Scand J Dent Res. 1983 Feb;91(1):66-71.