Diurnal variation of hepatic glutathione concentration and its correlation with 1,1-dichloroethylene inhalation toxicity in rats.
Jaeger-RJ; Conolly-RB; Murphy-SD
Res Commun Chem Pathol Pharmacol 1973 Sep; 6(2):465-471
Hepatic glutathione (GSH) concentrations and inhalation toxicity of 1,1-dichloroethylene (75354) (DCE) were determined in fed and fasted rats. Male Holtzman-rats were allowed free access to food and water or were fasted for 18 hours prior to testing. In the first experiment, fed and fasted animals were sacrificed at 3 hour intervals for 24 hours, and GSH concentrations in the liver were determined by a colorimetric method. Other groups of fed rats were exposed to 2000 parts per million DCE at about noon or midnight. After 24 hours, the rats that had not died were killed and examined for liver damage; serum alanine-alpha-ketoglutarate-transaminase (SAKT) activity was also measured as an indicator of undetected liver injury. Between 4 and 10 PM, fed rats showed a decline in GSH from about 8.5 to about 5.3 milligrams (mg) per 100 grams (g) body weight. GSH then gradually rose to reach about 8.7 mg per 100 g by 1 PM the next day. Fasted rats showed a similar circadian rhythm, but all values were depressed, fluctuating between about 4.0 and 5.5mg per 100g. Fed rats exposed to DCE at noon had no deaths and showed a threefold increase in SAKT. Two of the five rats exposed at midnight died, and survivors showed no apparent liver damage but had nearly 100 times normal SAKT values. The authors conclude GSH protects against both lethality and liver injury induced by DCE.
NIOSH-Publication; NIOSH-Grant; Grants-other; Pharmacology; Chemical-structure; Chemical-properties; Inhalants; Toxicology; Toxicopathology; Biochemical-tests; Hepatotoxicity; Animal-studies
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Other Occupational Concerns; Grants-other
Research Communications in Chemical Pathology and Pharmacology
Harvard University, Boston, Massachusetts