Simultaneous exposure of non-diabetics to high levels of dioxins and mercury increases their risk of insulin resistance.

"simultaneous exposure to dioxins and mercury heightens the risk of insulin resistance more than does individual exposure."


Read abstract: CiteULike: Simultaneous exposure of non-diabetics to high levels of dioxins and mercury increases their risk of insulin resistance.:

Chronic metals ingestion by prairie voles produces sex-specific deficits in social behavior: an animal model of autism.

"chronic metals exposure may contribute to the development of autism, possibly by interacting with central dopamine function, and support the use of prairie voles as a model organism in which to study autism."


CiteULike: Chronic metals ingestion by prairie voles produces sex-specific deficits in social behavior: an animal model of autism.:

Mercury Induces Oxidative Stress, Altering Nrf2 Microglial~!

"Consistent with the nuclear translocation of Nrf2, quantitative real-time PCR revealed a concentration-dependent increase in the messenger RNA level of Ho-1, Nqo1, and xCT 30 min post MeHg exposure, whereas Nrf2 knockdown greatly reduced the upregulation of these genes. Furthermore, we observed increased microglial death upon Nrf2 knockdown by the small hairpin RNA approach. Taken together, our study has demonstrated that microglial cells are exquisitely sensitive to MeHg and respond rapidly to MeHg by upregulating the Nrf2-mediated antioxidant response."

CiteULike: Methylmercury Induces Acute Oxidative Stress, Altering Nrf2 Protein Level in Primary Microglial Cells:

Heavy Metals, Metallothionein and Regulation by Nrf2

Metallothionein: protein that modulates internal stores of heavy metals. Alterations in function have been recently implicated in autism as well as, other conditions where metals may be a factor including metabolic impairments and Alzheimer's.

In several past blogs, we have discussed health benefits of broccoli because it elevates the Nrf2 antioxidant system. In contrast to the preceding blog where it was noted that metallothioneins can inhibit GSK-3b which is an off/on switch for Nrf2 it has also be demonstrated that metalloproteins can be regulated by Nrf2. In 2005, Yeh's study suggested that sulphoraphane, "strongly suggest that at low concentrations of sulforaphane, activation of MAPKs such as ERK and p38 pathway lead to Nrf2-mediated metallothionein gene expression." One can assume from this that conditions that impair the Nrf2 system may lead to possible accumulation of toxic amounts of metals that can impair any number of metabolic processes. Such conditions include methylation, nutrition and other genetic factors such as polymorphisms, for example. Of course, this does not exclude factors that impair metallothionein on its own.

Notes:

• metallothionein expression needs to be tightly regulated because underexpression or overexpression can help mitigte or enhance disease.

HEIRS Library Tags: heavy metals, sulphoraphane (sulforaphane), Nrf2*****Sign up to receive alerts of heavy metal articles

            Blog Tags: Broccoli, sulforaphane, Nrf2

Recommended:
**Bookstore
















***Garden Store

Broccoli Seeds





Raymond, A. D., Gekonge, B., Giri, M. S., Hancock, A., Papasavvas, E., Chehimi, J., Kossevkov, A. V., Nicols, C., Yousef, M., Mounzer, K., Shull, J., Kostman, J., Showe, L., and Montaner, L. J. (2010). Increased metallothionein gene expression, zinc, and zinc-dependent resistance to apoptosis in circulating monocytes during hiv viremia. Journal of leukocyte biology.

http://www.citeulike.org/user/HEIRS/article/7369487


Yeh, C.-T. and Yen, G.-C. (2005). Effect of sulforaphane on metallothionein expression and induction of apoptosis in human hepatoma hepg2 cells. Carginogenesis Advance Access.

http://www.citeulike.org/user/HEIRS/article/7369321

Sabolić, I., Breljak, D., Skarica, M., and Herak-Kramberger, C. M. (2010). Role of metallothionein in cadmium traffic and toxicity in kidneys and other mammalian organs. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine.

http://www.citeulike.org/user/HEIRS/article/7369302

RhCG Protein Active Ammonia Transporter - Reversed by Metals.

"The major finding of this study is that RhCG protein is active as an NH(3) channel and that this function does not require any protein partner. This strong NH(3) transport was reversibly inhibited by mercuric and copper salts.

Notes:

• Acidosis changes expression transporter RhCG. (Sechadri)

CiteULike: Functional reconstitution into liposomes of purified human RhCG ammonia channel.: "Mouro-Chanteloup, I., Cochet, S., Chami, M., Genetet, S., Zidi-Yahiaoui, N., Engel, A., Colin, Y., Bertrand, O., and Ripoche, P. (2010). Functional reconstitution into liposomes of purified human rhcg ammonia channel. PloS one, 5(1)."

Seshadri, R. M., Klein, J. D., Smith, T., Sands, J. M., Handlogten, M. E., Verlander, J. W., and Weiner, D. I. (2006). Changes in subcellular distribution of the ammonia transporter, rhcg, in response to chronic metabolic acidosis. Am J Physiol Renal Physiol, 290(6):F1443-1452.
http://www.citeulike.org/group/5070/article/2944496
Lim, S. W., Ahn, K. O., Kim, W. Y., Han, D. H., Lie, C., Ghee, J. Y., Han, K. H., Kim, H.-Y., Handlogten, M. E., Kim, J., Yang, C. W., and Weiner, I. D. (2008). Expression of ammonia transporters, rhbg and rhcg, in chronic cyclosporine nephropathy in rats. Nephron- Experimental Nephrology, 110(2). http://www.citeulike.org/user/HEIRS/article/6777343

Ammonia Enzymes, Immune Cells & X-Linked Mutations In Autoimmunity and Disease

Background: We have suggested that environmental illnesses may involve the loss of suppression of regulatory T cells and that several different proteins may be involved which changes the dynamics or "immunological footprint" of these conditions in each individual. Previously we mentioned how high ammonia levels may account for some of the symptoms associated with multiple chemical sensitivity. We also noted recently how alterations in ornithine enzymes may effect ammonia levels and the Nrf2 gene regulator has some control over its expression. The following article discusses findings related to how a mutation in ornithine transcarbamalase may influence the immune system and play a role in autoimmune type disease. Interestingly, the author points out the condition is X-linked which might account for higher number of females presenting with them because males usually die in utero and do not live but a few days after birth. There is usually a large sexual dimorphism in the prevalence of many environmental diseases. As Li explains, there may be a number of factors that contribute to autoimmune disease which may include estrogenic production as well as, vulnerable phenotypes may be more susceptible to metals exposure which may accelerate some individuals to reactive phenotypes. (Li)

The author writes, "Antigen expression in the thymus leads to the deletion of self-reactive T cells and generation of regulatory lymphocytes, including regulatory T cells(Treg) and NKT cells. We show an Ornithine transcarbamylase(OTC) mutation causes ineffective presentation of self antigens in the thymus. As such, deletion of self reactive T cells is compromised and production of Treg and NKT cells is reduced in the OTC mutant mice. More importantly the heterozygous mice have increased susceptibility to autoimmune diseases, including the generation of autoantibodies and more severe EAE." Further, "OTC mutant mice, the production of Treg in the thymus is reduced, which is correlated with the impaired antigen presentation due to hyperammonemia."


Comment: This article is a good representation of why only qualified medical professionals that understand the multitude of genetic conditions and environmental conditions that activate them should be treating them. There is no evidence thus far, that a "therapeutic recipe" is effective at treating all of them.


Chang, X. (2006). X linked foxp3 & otc in immune tolerance and autoimmunity. Ohio State University. http://www.citeulike.org/user/HEIRS/article/6650098
Li, J., Stein, T. D., and Johnson, J. A. (2004). Genetic dissection of systemic autoimmune disease in nrf2 deficient mice. Physiological Genomics.
http://www.citeulike.org/user/HEIRS/article/6604948

Burning Charcoal: Sources of VOC, Carbonyls, Toluene, Formaldehyde and Mercury

Kabir, E., Kim, K.-H. H., Ahn, J.-W. W., Hong, O.-F. F., and Sohn, J. R. R. (2010). Barbecue charcoal combustion as a potential source of aromatic volatile organic compounds and carbonyls. Journal of hazardous materials, 174(1-3):492-499. http://www.citeulike.org/user/HEIRS/article/5841732

Pandey, S. K. K., Kim, K.-H. H., Kang, C.-H. H., Jung, M. C. C., and Yoon, H. (2009). Bbq charcoal as an important source of mercury emission. Journal of hazardous materials, 162(1):536-538. http://www.citeulike.org/user/HEIRS/article/6433445

The usefulness of chelation therapy for the remission of symptoms caused by previous treatment with mercury-containing pharmaceuticals: a case report

Introduction A great deal of data regarding the toxicology of mercury has been recently reported. Although the most common human exposures to mercury are currently mercury vapour from amalgam tooth fillings, methylmercury from seafood and ethylmercury as a preservative in vaccines, in the past mercury compounds have been used in the treatment

LINK

Study Examines Mercury in Vaccines

"Dr. Pichichero and colleagues concluded that with this latest data, it is time to recognize that the risk of exposure to thimerosol in vaccines is minimal to non-existent. “The H1N1 vaccine is safe and should be given to those at risk as recommended by the US Centers for Disease Control”, Dr. Pichichero said."

Link

Study Examines Mercury in Vaccines. Medwise. Retrieved on October 30, 2009.

Mercury Levels In Children With Autism And Those Developing Typically Are The Same, Study Finds

Mercury Levels In Children With Autism And Those Developing Typically Are The Same, Study Finds

ScienceDaily (2009-10-20) -- In a large population-based study, researchers report that after adjusting for a number of factors, typically developing children and children with autism have similar levels of mercury in their blood streams. ... > read full article

Mercury Linked to High Blood Pressure in Native Canadians

Mercury Linked to High Blood Pressure in Native Canadians

Groundbreaking Primate Study Links Mercury Vaccine Preservative To Brain Injury

Groundbreaking Primate Study Links Mercury Vaccine Preservative To Brain Injury

Probucol Increases Glutathione Peroxidase-1 Activity and Displays Long-Lasting Protection Against Methylmercury Toxicity in Cerebellar Granule Cells

Probucol is an anti-hyperlipidemic drug that was initially developed to treat coronary artery disease. (Wipedia)

Probucol Increases Glutathione Peroxidase-1 Activity and Displays Long-Lasting Protection Against Methylmercury Toxicity in Cerebellar Granule Cells

The Mechanisms of Heavy Metal Cytotoxicity!

Different metals have different mechanisms for toxicity. In flies, DAF-16, the homolog of the FOXO family in humans, can be effected by exposure to different metals which activate cell signaling pathways to achieve it. Copper is an insulin mimetic and long-term exposure may result in insulin resistance and it inhibits the G-6-P promoter which is important in the healthy maintenance of glutathione (See figure)and is regulated by FOXO and insulin.

Mercury has significant effects on Nrf2 expression in monocytes for awhile but inhibits thioredoxin. Wataha explains monocytes can adapt to trace amounts of mercury that are introduced through the environmental such as dental work and fish consumption and will not compromise immune function. Because the Nrf2 pathway is involved, its normal function is imperative to this adaptive response. Messer et al demonstrated that mercury did not generate oxidative stress in his study but did alter redox states at levels that are not generally considered as chronic mercury toxicity. The levels he tested were levels common in the blood of patients that have had dental work and also showed a decrease in mitochondrial activity of 50% at relatively low Hg levels. Lewis demonstrated that nickel may dysregulate cytokine production and the amount of influence may depend on Nrf2 but with no interaction of FOXO, no oxidative stress or cytotoxic effects(Eckers). Copper on the other hand, is 100 times more toxic than nickel. Cadmium elicits endoplasmic reticulum stress (Hiramatsu).

Citations to Original Document