Subj: [GWVM] Short-Term Exposures to Chemicals & Stress Damage Brain & Liver
Date: 2/27/2004 1:05:42 PM Eastern Standard Time
From: "Ashley" <ahotz@...>
http://www.ascribe.org/cgi-bin/spew4th.pl?ascribeid=20040226.123126&time
=13%2031%20PST&year=2004&public=1
Thu Feb 26 13:31:16 2004 Pacific Time
Mix of Chemicals Plus Stress Damages Brain, Liver in Animals and Likely
in Humans
DURHAM, N.C., Feb. 26 (AScribe Newswire) -- Stress is a well known
culprit in disease, but now researchers have shown that stress can
intensify the effects of relatively safe chemicals, making them very
harmful to the brain and liver in animals and likely in humans, as well.
Even short-term exposure to specific chemicals -- just 28 days -- when
combined with stress was enough to cause widespread cellular damage in
the brain and liver of rats, said Mohamed Abou Donia, Ph.D., a Duke
pharmacologist and senior author of the study.
Results of the study were published in the Feb. 27, 2004, issue of the
Journal of Toxicology and Environmental Health.
Abou Donia's study was designed to reproduce the symptoms of Gulf War
Syndrome, a disorder marked by chronic fatigue, muscle and joint pain,
tremors, headaches, difficulties concentrating and learning, loss of
memory, irritability and reproductive problems. The Gulf War Syndrome
symptoms have been difficult to explain because veterans outwardly
appear healthy and normal, said Abou Donia. Likewise, the chemically
exposed animals in Abou Donia's studies looked and behaved normally.
But a decade of neurologic research has revealed widespread damage to
the brain, nervous system, liver and testes of rats exposed to 60 days
of low-dose chemicals -- the insect repellant DEET, the insecticide
permethrin, and the anti-nerve gas agent pyridostigmine bromide. These
are the same drugs that the soldiers received during the 1990 - 1991
Persian Gulf War, and Abou Donia's rats were exposed to the same levels
-- in weight adjusted doses -- as the soldiers were reportedly given.
Now, Abou Donia has demonstrated that the combination of stress and
short-term exposure to chemicals (28 days) can promote cellular death in
specific brain regions and injury to the liver. Moreover, the chemical
trio combined with stress caused damage to portions of the brain where
its protective blood-brain barrier was still intact.
The latter finding suggests that the chemicals permeated the protective
barrier in one region, then leaked into other regions of the brain where
the barrier remained intact. The ability of chemicals to leak from one
area of the brain to another holds the potential for much greater damage
to occur to the entire brain.
Brain regions that sustained significant damage in this study were the
cerebral cortex (motor and sensory function), the hippocampus (learning
and memory) and the cerebellum (gait and coordination of movements).
Abou Donia's earlier studies demonstrated severe damage to the cingulate
cortex, dentate gyrus, thalamus and hypothalamus.(The thalamus is the
major relay for visual and auditory information going to the cortex and
is also responsible for subjective feelings. The hypothalamus regulates
metabolism, sleep and sexual activity, as well as control of emotions.)
Abou Donia's team found a significant number of dead or dying brain
cells in all of these brain regions, as well as major alterations to
brain chemicals that are necessary for learning and memory, muscle
strength and body movement. Stress alone caused little or no brain
injury in the rats, nor did the three chemicals given together in low
doses for 28 days.
"But when we put the animals under moderate stress by simply restricting
their movement in a plastic holder for five minutes at a time every day,
the animals experienced enough stress that it intensified the effects of
the chemicals dramatically," said Abou Donia.
Soldiers in the Gulf War were likely under stress 24 hours a day for
weeks or months at a time, a scenario which could explain the origins of
their diverse physical and cognitive complaints, said Abou Donia.
"The brain deficits we found in rats reside in specific areas of the
brain that we can't measure in living humans," said Abou Donia. "This is
why the deficits are so difficult to assess clinically and why animal
studies are so critical to understanding the cellular damage."
In addition to brain injuries, the Duke study found unexpected damage to
the liver, including swollen cells, congested blood vessels and abnormal
fatty deposits that diminish the liver cells' function. Liver cells also
showed reduced activity of an important enzyme -- BuCHE -- that helps
rid the body of some toxic substances. Neither stress by itself nor
chemicals alone had any impact on BuCHE levels, but the combination did.
Such damage to the liver can reduce its ability to rid the body of toxic
substances -- its primary function as a vital organ. And, the less
effectively the liver filters out toxic substances, the more the
chemicals can concentrate in the brain and nervous system, he added.
Finally, the study showed that stress plus chemicals increased the
amount of destructive molecules in the brain called reactive oxygen
species -- also known as oxygen free radicals. Reactive oxygen species
are produced by the body as it metabolizes various substances in the
presence of oxygen.
Reactive oxygen species attack DNA, RNA and proteins, causing cellular
and membrane damage. Normally, the body removes these chemicals from the
body and the brain. But excessive production of reactive oxygen species
can overwhelm the body's ability to dispose of them.
"In our study, there was an increase in reactive oxygen species. We
think that either the three chemicals and stress directly produce these
free radicals, or the chemicals impede the body's ability to get rid of
them," said Abou Donia.
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