Research Category:

FY: 2005 Funding (in dollars): 91,000

Responsible Organization: AIR FORCE RESEARCH LAB/WRIGHT PATTERSON
Primary Contact: See Responsible Organization Information
City: Wright-Patterson AFB
State: OH
Zip: 45433-7902

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.