Links Between
Multiple Chemical Sensitivity
and Asthma in a Rat Model
of Cholinergic Hypersensitivity: a Brief Review
Toxicology and Industrial
Health
August 1999, Volume 15, Issue 5, Pages
517 - 521
DAVID H.
OVERSTREET*
& VELJKO DJURIC
ABSTRACT
Individuals with multiple chemical sensitivity (MCS) also commonly report
symptoms of asthma, but, as far as we have been able to determine, no one
has yet suggested that an abnormal cholinergic
system may provide the
link between asthma and MCS.
The present brief review provides evidence for such a link by summarizing
recent findings in a genetic animal model of cholinergic
hyperresponsiveness.
The Flinders Sensitive Line (FSL) rats were developed
by selective breeding
for increased responses to
an anticholinesterase agent
similar to commonly
used organophosphate pesticides.
Relative to their control line, the Flinders Resistant Line (FRL) rats, the
FSL
rats are more sensitive to
drugs that stimulate acetylcholine receptors,
alcohol,
diazepam, and drugs that have a selective effect on dopamine or serotonin
receptors.
These findings raise the possibility that the FSL rats may resemble individuals
with MCS.
Hyperresponsiveness of the airways is a hallmark of asthma.
The procedure known as whole-body plethysmography, where breathing
can be monitored in freely moving animals, was employed to study the FSL
and FRL rats. The FSL rats exhibited a greater index of bronchoconstriction
than the FRL rats in response to both a cholinergic
agonist and an allergen
challenge.
Thus, the FSL rats are more
sensitive both to a
variety of drugs
unrelated
to the cholinergic system and to cholinergic-
and allergen-induced
bronchoconstriction.
An abnormal cholinergic system may therefore contribute to both MCS
and asthma.
[NOTE:
Marie did
not
have any respiratory or asthmatic symptoms
before
the exposures to the unethically and
illegally applied pesticides and solvents
at Southwest Baptist
University.
Severe exposure to these toxins caused permanent changes and damage
to Marie's cholinergic system due to
the
refusal of SBU officials
to provide
her with the timely and required medical
care and information
on
these
cholinesterase inhibiting
pesticides.
As stated in emedicine: EMERGENCY MEDICINE:
An on-line Medical
Reference under
Toxicity,
Organophosphate and
Carbamate:
...
Exposure to organophosphates and carbamates
produces a characteristic,
treatable syndrome in
humans. Its recognition and timely intervention
is
of great importance to emergency physicians and their
patients.
Organophosphates
irreversibly
bind to
cholinesterase causing the
phosphorylation and deactivation of
acetylcholinesterase. The subsequent
accumulation of acetylcholine
at the neural synapse causes an initial
overstimulation followed by eventual
exhaustion and disruption of neural
transmission in the central and peripheral nervous systems
(CNS and PNS).
If the organophosphate/cholinesterse
bond is not broken by
pharmacologic
intervention [that is, the administration of the
antidote (atropine sulfate)
and other drug therapies] within
24 hours, large amounts of cholinesterase
are destroyed causing long-term morbidity or death.
...
Had the antidote been administered promptly, the damage due to the
permanent
and irreversibly
binding of
the
organophosphates to
the cholinesterase receptors
would have been minimized.
Medical authorities now recognize the link between the
disruption of the
cholinergic system by organophosphate
pesticides and other chemicals
as one of three primary
causes of
Occupational Asthma.
As the American Academy of Allergy, Asthma,
and Immunology (AAAAI)
describes in its
literature
on Occupational Asthma:
Occupational Asthma:
Causes
Occupational asthma may be
caused by one of three mechanisms.
These include:
*Direct irritant effects ...
*Allergy (long-term exposure) ...
*Pharmacologic
mechanisms
Inhalation of some substances in aerosol form
can directly lead
to the accumulation of naturally occurring
chemicals in the body,
such as
histamine or acetylcholine
within the lung, which in turn
lead to asthma.
For example,
insecticides, used in agricultural work {or
in illegal,
indoor
applications at Southwest Baptist University},
can cause a
buildup of
acetylcholine, which
causes airway muscles to contract,
thereby
constricting
airways. ]
For more information on cholinergic responses to toxins, please
see:
Congressional Testimony on Chemical
Intolerance
and Toxicant Induced Low Tolerance
(TILT) October 26, 1999
Dr. Claudia Miller
~~*~~
Correspondence to:
*DAVID
H. OVERSTREET , David H. Overstreet,
Ph.D.,
Bowles Center for Alcohol Studies, CB 7178, 3011 Thurston-Bowles Building,
University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7178.
Tel.: (919)966-5678. Fax: (919)966-5679.
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