Aging effects on acetaminophen toxicity and glutathione status in the mosquito

John Richie, C. A. Lang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 < 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 < 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.

Original languageEnglish (US)
Pages (from-to)14-17
Number of pages4
JournalDrug Metabolism and Disposition
Volume13
Issue number1
StatePublished - Jan 1 1985

Fingerprint

Acetaminophen
Culicidae
Lethal Dose 50
Aedes
Glutathione
Young Adult
3-(glutathion-S-yl)acetaminophen

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

@article{28172a192ce448a99c5c7c6200b8367d,
title = "Aging effects on acetaminophen toxicity and glutathione status in the mosquito",
abstract = "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 < 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 < 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.",
author = "John Richie and Lang, {C. A.}",
year = "1985",
month = "1",
day = "1",
language = "English (US)",
volume = "13",
pages = "14--17",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "1",

}

Aging effects on acetaminophen toxicity and glutathione status in the mosquito. / Richie, John; Lang, C. A.

In: Drug Metabolism and Disposition, Vol. 13, No. 1, 01.01.1985, p. 14-17.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Aging effects on acetaminophen toxicity and glutathione status in the mosquito

AU - Richie, John

AU - Lang, C. A.

PY - 1985/1/1

Y1 - 1985/1/1

N2 - 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 < 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 < 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.

AB - 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 < 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 < 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.

UR - http://www.scopus.com/inward/record.url?scp=0021984409&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021984409&partnerID=8YFLogxK

M3 - Article

VL - 13

SP - 14

EP - 17

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

SN - 0090-9556

IS - 1

ER -