Comments Andy? Is NAC not the answer.

[Guest guest]

In the 1930s, Eli Lily developed Thimerosal as a reservative 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 mg/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 mmol/L [micromoles per liter] to 5, 10,

and 20 mmol/L. Viability was reduced more than

50% in both cell lines with exposure to 10 mmol/L Thimerosal and less

than 10% of cells survived a dose of 20 mmol/L. "

The authors then pretreated cells with NAC before adding a dose of 15

mmol/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