Thimerosal neurotoxicity and protection with N-Acetylcysteine supplementation

http://www.healthsentinel.com/news.p..._item&id=3D511

Roman Bystrianyk, "Thimerosal neurotoxicity and protection with
N-Acetylcysteine supplementation", Health Sentinel, January 3, 2005,

In the 1930s, Eli Lily developed Thimerosal as a preservative and it
was widely used in vaccines. Until the removal of Thimerosal, which
contains 49.9% ethyl mercury by weight, from most pediatric vaccines in
2001, the source of the largest human exposure to mercury in the US was
in children under 18 months of age undergoing routine childhood
immunization schedules. Before 2001, a child may have received a
cumulative dose of over 200 =B5g/kg (micrograms per kilogram) in the
first 18 months of life.

Although Thimerosal has been removed from most childhood vaccines, it
is still present in the flu vaccine, which is given to pregnant women,
the elderly, and children. Also, many vaccines given to children in
developing countries still contain Thimerosal.

In the 2005 issue of NeuroToxicology, the authors of a study examine
the toxicity of Thimerosal within the body including neurons. They
examine the neurotoxic mechanisms, how the body detoxifies mercury, and
the use of N-Acetylcysteine, or NAC for short, in facilitating the
detoxification pathway within the body.

Glutathione, a tripeptide composed of cysteine, glutamate, and glycine,
is manufactured in the liver and also in the brain. Normally, the
concentrations of glutathione in the cells are quite high providing for
detoxification of a variety of heavy metals including mercury. However,
when this essential antioxidant is depleted the excess mercury can bind
to internal cellular proteins leading to toxic damage. Studies have
shown that, "low micromolar concentrations of Thimerosal induced DNA
strand breaks, caspase-3 activation, membrane damage and cell death."

Although the brain can produce glutathione, it can only manufacture
this from its immediate precursor cysteine. The liver, on the other
hand, is able through a long series of biochemical steps to create
glutathione from methionine. Methionine is an essential amino acid that
supplies the body with sulfur and methyl groups. The liver uses a
number of enzyme systems along with various B vitamins to produce
glutathione. The liver then exports the glutathione to the blood that
then is broken down to cystine. Cystine crosses the blood-brain barrier
to be used by the brain to make glutathione. Thus, the brain is reliant
on the liver to manufacture chemicals to keep it free from toxins.

The brain contains neurons and other cells called astrocytes.
Astrocytes use the cystine that crosses the blood-brain barrier to make
glutathione. The astrocytes then export the glutathione to the space
between the cells where it is broken down to cysteine. The neurons take
up the cysteine and manufacture glutathione. This complex series of
biochemical events is what is necessary to keep the brain free from
heavy metal damage.

The authors first examined the level of Thimerosal that would cause
toxic damage to cells. They found that the higher the concentration of
Thimerosal the greater the number of cells that were killed although
the nerve cell response occurred with only a 3 hour exposure, whereas
the other cell line required a 48 hour exposure demonstrating that
nerve cells are more sensitive to Thimerosal toxicity. "In both cell
lines, a progressive increase in cytotoxicity (decrease in viability)
was observed when Thimerosal dose was progressively doubled from 2.5
=B5mol/L [micromoles per liter] to 5, 10, and 20 =B5mol/L. Viability was
reduced more than 50% in both cell lines with exposure to 10 =B5mol/L
Thimerosal and less than 10% of cells survived a dose of 20 =B5mol/L."

The authors then pretreated cells with NAC before adding a dose of 15
=B5mol/L Thimerosal. They found that, "Thimerosal alone induced more
than a 6-fold decrease in viability", and that NAC, "provided
significant protection against cell death". The authors note,
"Thimerosal induces oxidative stress and apoptosis by activating
mitochondrial cell death pathways. A subsequent study using cultured
human neuron and fibroblast cell lines similarly showed that low
micromolar concentrations of Thimerosal induced DNA strand breaks,
caspase-3 activation, membrane damage and cell death."

The authors conclude that, "numerous clinical studies have
demonstrated the efficacy of NAC in increasing intracellular
glutathione levels and reducing oxidative stress in humans. Since
cytotoxicity with both ethyl- and methyl- mercury have been shown to be
mediated by glutathione depletion, dietary supplements that increase
intracellular glutathione could be envisioned as an effective
intervention to reduce previous or anticipated exposure to mercury.
This approach would be especially valuable in the elderly and in
pregnant women receiving Rho D immunoglobulin shots, and individuals
who regularly consume mercury-containing fish."
SOURCE: NeuroToxicology, Vol. 26, 2005, pp. 1-8