Inhibition of N-nitrosodimethylamine metabolism in rats by ether anesthesia

Short-term exposure to diethyl ether strongly inhibits the metabolism of N-nitrosodimethylamine (NDMA). Twenty-six 6-week-old male Fischer 344 rats were exposed to ether vapor until their righting reflex was lost (approximately 2 min). The animals were removed from the ether and NDMA was immediately...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1985-11, Vol.45 (11), p.5457-5460
Main Authors: KEEFER, L. K, GARLAND, W. A, OLDFIELD, N. F, SWAGZDIS, J. E, MICO, B. A
Format: Article
Language:English
Subjects:
Anesthesia
Animals
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Chemical agents
Dimethylnitrosamine - metabolism
Drug Interactions
Ether - metabolism
Ether - pharmacology
Ethyl Ethers - pharmacology
Male
Medical sciences
Rats
Rats, Inbred F344
Tumors
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Summary:Short-term exposure to diethyl ether strongly inhibits the metabolism of N-nitrosodimethylamine (NDMA). Twenty-six 6-week-old male Fischer 344 rats were exposed to ether vapor until their righting reflex was lost (approximately 2 min). The animals were removed from the ether and NDMA was immediately administered by i.v. bolus injection at a dose of 300 microgram/kg via a cannula surgically inserted 20 h earlier. A second group of 28 rats received injections of NDMA in an identical manner but without ether exposure. In the unanesthetized animals blood levels of NDMA declined with a half-life of 11 min; by contrast essentially constant blood levels of NDMA were observed in ether-treated animals for 120 min after removal from the anesthetic. The apparent total systemic clearance for the 5-h experiment was reduced from 43 ml/min/kg without ether to 5 ml/min/kg with ether. Diethyl ether has been found previously to inhibit the metabolism of other drugs requiring oxidative metabolism but the suppression of clearance documented here appears to be unusually pronounced. It is recommended that ether's potential for altering metabolic rates be carefully considered when planning or interpreting animal experiments.
ISSN:0008-5472
1538-7445