Sensitization By Dr Martin Pall
sensitization occurs by activation of brain and nerve cell N-methyl-D-aspartate(NMDA),
which then increases brain nitric oxide (NO).1,2,3 Several vicious
biochemical cycles are then set in motion.
Nitric oxide forms a tissue damaging free radical known as peroxynitrite.2,4,5,6
Peroxynitrite depletes energy TP,7,8 which then
further increases the sensitization of NMDA. 9,10
exposure can induce sensitization. Pesticides
such as organophosphates inhibit acetylcholine, acitivating muscarinic
receptors, which increase nitric oxide. Formaldehyde
(VOC’s, solvents) disrupt energy production in the nitochondria, increase
super oxide which increases peroxynitrite.12 This can then increase
tissue-damaging free radicals in the brain.13 Mitochondrial
disruption occurs in chemically injured patients.14 Petrochemicals
and many other chemicals are irritants15 that with exposure can cause
inflammation. Inflammation of
sufficient duration can lead to chronic neurogenic inflammation.16
Inflammation results in increased cytokines, free radicals and elevated nitric
sensitization is thus associated with self-perpetuating neuroexcitation and
excessive response to further chemical exposure.11,17
This NMDA activation with increased nitric oxide and peroxynitrite can
cause brain cell death and neurogenerative disease.2,6,10,18,19,20
Peroxynitrite also weakens the blood-brain barrier, allowing chemicals to
enter the brain more readily.21
Nitric oxide also damages the first detoxification step involving the
cytochrome p450 system,22 allowing chemicals (and many drugs) to
build up more in the body.
vicious cycle MUST therefore be interrupted to the maximum extent feasible.
Because the resulting symptoms of sensitization are warnings that other
more silent toxic-induced organ damage of the liver, pancreas, immune system,
adrenals, mitochondria and other organs can be also occurring,16,23,24
symptoms of this cycle is not recommended without healing the disturbed
biochemical mechanism. (This would
be like turning off a battery warning light without fixing the battery.)
Cobalamine(B12) is a nitric oxide scavenger and deficient in the majority
of chemically ill patients. The
cyano form is not recommended (these patients don’t need cyanide and the
hydroxy and methyl forms work much better in the brain and nerve cells).
Superoxide dismutase is deficient in a significant portion of chemically ill
patients and its cofactors, copper, zinc, and manganese must be adequate.
These are often reduced in chemically injured patients and should be
tested and replaced in well-absorbed and transported forms, for example,
picolinates. Antioxidant function
is usually inadequate in chemically ill patients,23 and increased lipid peroxides and other free radicals are
to help reduce this vicious biochemical cycle includes: methyl or
hydroxycobalamine sublingually or I.M. (not oral due to poor absorption),
general antioxidants (C, E, selenium), glutathione by nebulizer due to poor oral
absorption, and ample alpha lipoic acid to reactivate the glutathione in the
many damaged lipid tissues (cell membranes, mitochondria, lymph, brain, etc,).
Trimethyl glycine is recommended as a methyl donor to reduce the effects
of peroxynitrite. Magnesiuim should
be ample because deficiency is very common with toxic injury and adequate
magnesium decreases NMDA activiation. Peroxynitrite
scavengers such as a mixture of caretenoids are also recommended.
Carentenoids tend to be more organ-specific. An inclusion of gingko (brain), silimarin (liver), bilberry
(collagen stabilizing, capillary permeability, vision), cranberry (urinary) and
other mixed caretenoids is recommended.
levels should be measured and followed by intercellular (eg.RBC) or lipid
functional (eg. Lymphocyte mitogenesis, a SpectraCell technology). Functional lymphocyte evaluaion and follow-up of glutathione,
lipoic acid, total antioxidant function, C, E and zinc is also recommended. At
this time this technology is only available through Spectra cell laboratory.
of the above is a substitute for exposure controls at home, work and /or places
where the person spends most of their time.
Humans are social beings, and these measures above gradually increase the
person’s ability to enjoy the company of others and use public places. When society is adequately informed and takes public health
accommodation measures to reduce irritants and toxins in personal products and
public places, this further promotes health and reduces sensitization.
Haley etal., “Evidence for spinal N-methyl-D-aspartate receptor involvement in
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Lafon-Cazal etal., “Nitric oxide, superoxide and peroxynitrite: putative
mediation of NMDA-induced cell death in cerebellar cells”, Neuropharmacology
Reynolds and TG Hastings, “Glutamate produces production of reactive oxygen
species in cultured forebrain neurons following NMDA receptor activation”,
Beckman, “The double edged role of nitric oxide in brain function and
superoxide-mediated injury”, J.Dev Physiol15:53-59, 1991.
Lafon-Cazal etal., “NMDA-dependent superoxide production and Neurotoxicity”,
Nature 364:535-537, 1993.
Coyle and P Puttfarken, “Oxidative stress, glutamate and neuro generative
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peroxynitrite formation”, Biochem Soc Trans21:330-333,1993
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reaction of nitric oxide and superoxide:, Am J.Physiol268:L699-L722,1995.
Novelli etal., “Glutamate becomes neurotoxic via the NMDA receptor when
intercellular energy levels become reduced”, Brain Res451:205-212,1988.
Schultz, etal., “The role of mitochondrial dysfunction and neuronal nitric
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redox-cyclers enforced by membrane derangement”, Z Natur forsch
Mattia etal., “Toluene-induced oxidative stress in several brain regions and
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Khatsenko etal., “Nitric oxide is a mediator of the decrease in cytochrome
p450-dependent metabolism caused by immunostimulants”, Proc Nat Acad Sci USA
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Following Chemical Overexposure.