Aging effects on acetaminophen toxicity and glutathione status in the mosquito.

Previously we found that a decrease in glutathione (GSH) concentration is a general phenomenon in aging organisms. This suggested our hypothesis that the capacity for detoxification involving GSH will decrease in senescence. Thus the present objectives were to determine the toxicity of acetaminophen (APAP) and its relationship to GSH status in the aging mosquito. Different concentrations of APAP in Aedes Ringer were injected into adult mosquitoes of different ages through the life-span. The results showed that the LD50 values were highest in the young adult, plateaued in the mature, and decreased 7-fold in the very old adults (p less than 0.0001). Of special interest was that these decreasing LD50 values were closely correlated with the aging-specific decreases in GSH concentration observed in our previous experiments (r = 0.99). Also a direct relationship was established as the administration of a lethal dose (LD50) of APAP depleted more than 99% of the GSH content (p less than 0.0001). This is the first demonstration of an aging-specific decrease in detoxification capacity in a well characterized aging model. Further, these findings suggest that GSH levels may serve as an indicator of vulnerability to other toxicants.