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Air Force Research Laboratory, Wright-Patterson AFB, OH
DOD Funding of Animal Cruelty 2005: Distribution of
N-acetyl-cysteine (NAC) in Sprague-Dawley rats following dermal
glutathione (GSH) depletion
Title: Distribution of N-acetyl-cysteine (NAC) in Sprague-Dawley
rats following dermal glutathione (GSH) depletion
FY: 2005 Funding (in dollars): 91,000
Responsible Organization: AIR FORCE RESEARCH LAB/WRIGHT
Primary Contact: See Responsible Organization Information
City: Wright-Patterson AFB
Keywords: LABORATORY ANIMALS GSH + SKIN + DEPLETION + MODEL
NAC + CELL CULTURE NAC + SKIN CELLS RAT + GSH + SKIN + DEPLETION
Objective: The objectives of this work are to: 1) demonstrate
that dosing with NAC by oral gavage restores glutathione levels in rat
skin treated with the GSH-depleting substance DEM, and 2) show that NAC
distributes to the skin following GSH depletion, which indirectly shows
that NAC given by the oral route can act as a source of cysteine in skin
cells for regenerating skin GSH levels. Our hypothesis is that
orally-administered NAC should restore GSH levels in rat skin previously
treated with DEM, a GSH-depleting substance.
Approach: Depletion of dermal glutathione (GSH) following
exposure to a GSH depletor: In the first study, we determined the
topical dose of diethyl maleate (DEM) required to significantly deplete
GSH from rat dorsal skin when assessed one and three hours after
application. GSH replenishment via NAC oral dosing: This was
accomplished by using radio-labelled cysteine portion of NAC to
determine if NAC was the source of cysteine in GSH replenishment. Three
experimental groups were used; DEM-only, NAC-only, and DEM + NAC.
Besides the skin, we also looked at urine and feces to determine if NAC
uptake/use was increased due to GSH replenishment. This was performed in
the adult rat model.
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Rats, mice, birds, amphibians and other animals have
been excluded from coverage by the Animal Welfare Act. Therefore research
facility reports do not include these animals. As a result of this
situation, a blank report, or one with few animals listed, does not mean
that a facility has not performed experiments on non-reportable animals. A
blank form does mean that the facility in question has not used covered
animals (primates, dogs, cats, rabbits, guinea pigs, hamsters, pigs,
sheep, goats, etc.). Rats and mice alone are believed to comprise over 90%
of the animals used in experimentation. Therefore the majority of animals
used at research facilities are not even counted.