APPENDIX II-Y:
Chemicals Used to Protect Soldiers in 1991 Gulf War Can Damage Testes,
Animal Studies Show
This appendix is copied from:
http://www.dukemednews.org/news/article.php?id=6326
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The new study could explain why some
veterans have experienced infertility, sexual dysfunction, and other
genitourinary symptoms, said Mohamed Abou Donia, Ph.D., a Duke pharmacologist. Three chemicals were given to soldiers to
protect them against insect-borne diseases and nerve-gas poisoning: the
insect repellent DEET, the insecticide permethrin,
and the anti-nerve gas agent pyridostigmine
bromide. In a study designed to mimic those same
conditions, Abou Donia and
his colleagues gave rats equivalent doses to what
the soldiers received. When given together, the chemicals caused extensive
cell degeneration and cell death with various structures of the testes, he
found. The damage was even more severe among rats that were exposed to
moderately stressful situations in addition to the chemicals. Results of the study, funded by the
Department of Defense, are published in the "It appears that moderate stress,
combined with the three chemicals, caused the most severe deterioration in
testicular structure and sperm production, and these conditions were likely
experienced by some Gulf War soldiers in the combat environment," said Abou Donia, principal
investigator of the study. "Interestingly, the chemically-treated
rats don't look or behave any differently than normal rats, just as the
soldiers don't show any outward signs of disease," said Abou Donia. "But under a
microscope, you can see clear and well-defined damage to a variety of
testicular structures." Abou Donia's team found the
most pervasive cell damage within basal germ cells and spermatocytes,
which give rise to mature sperm. The three chemicals combined with stress
caused these cells to detach from one another, slough off, and develop holes
known as "vacuoles." Such changes are well-known stages in the
progression toward programmed cell death, known as apoptosis. The more cells
that die, the greater the suppression of "spermatogenesis" or sperm
production, said Abou Donia.
In fact, pathologic exams showed that most
of the developing stages of sperm were interrupted, and some of the stages
were absent altogether among rats treated with all three chemicals and
stressful conditions. Similar cell degeneration occurred in the seminiferous tubules, where developing sperm are
produced, and Sertoli cells that support and
nurture the developing germ cells. "On every objective measure, the
testes showed severe degeneration in the presence of multiple chemicals,
suggesting that the chemicals have a synergistic or additive effect,"
said Abou Donia. BRAIN DEFICITS COINCIDE WITH REPRODUCTIVE
DAMAGE The testicular damage corresponds to
equally devastating brain changes in the same rats exposed to the chemicals
plus stress, said Abou Donia.
Findings from those experiments were published in the August 2002, issue of
Neurobiology of Disease. In that study, Abou
Donia's team showed that chemicals and stress
increased the permeability of the blood-brain barrier, allowing substances
that would normally be blocked to enter the brain. Moreover, the researchers
found large numbers of dead neurons, or nerve cells, in regions of the brain
that control muscle strength and movement (cortex); balance and coordination
(cerebellum); and memory, cognition and mood (hippocampus). Yet the animals
appeared normal to the naked eye. Similarly, Gulf War veterans have
complained of deficits in these very functions for more than a decade, while
clinical exams show no obvious signs of disease. "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." Complicating the diagnostic process even
further is the sheer volume of brain cells that must die before clinical
deficits become obvious, he said. The human brain contains billions of nerve
cells and supporting cells, so the loss of brain cells does not produce
immediate and overt symptoms. Often, it takes repeated exposures to chemicals
before the brain is depleted of enough neurons to trigger deficits, he said. However, once the damage occurs, little can
be done to repair it. Extensive nerve cell death causes "holes" in
the brain and thus permanent deficits, because neurons cannot regenerate like
other cells in the body. "Many of the effects we see with
chemical exposure are similar to those of aging, which is also associated
with fewer neurons," said Abou Donia. He said his ongoing research should help prevent
such debilitating conditions in the future. "The military used these chemicals
with the best of intentions, to protect soldiers from indigenous diseases in
the Gulf War region," he said. "Without protection, there may have
been thousands of deaths. But it appears that the precautions prevented one
set of problems while creating another. Now, our task is to discern the
mechanisms of illness in order to provide the soldiers with maximum
protection and the least risk of chemically induced injury." Duke colleagues Hagir
B. Suliman, Ph.D., Wasiuddin
A. Khan, Ph.D., and Ali A. Abdel-Rahman were
co-authors of the paper. |
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