Modification of the effects of chloroform on the rat liver
TLDR
Investigations with chloroform anaesthesia in rats pretreated with phenobarbitone indicate that the hepatotoxic action of chloroforms is directly related to the activity of the microsomal drug-metabolizing enzymes.Abstract:
SUMMARY Investigations with chloroform anaesthesia in rats pretreated with phenobarbitone indicate that the hepatotoxic action of chloroform is directly related to the activity of the microsomal drug-metabolizing enzymes. Pretreatment with disulfiram, an inhibitor of the enzymes in man and rats, completely prevents the hepatotoxicity of chloroform in rats. It would seem that the toxic effects of chloroform on the liver are due to toxic metabolites, the nature of which remains unknown. The enzymes responsible for the production of the toxins appear to be located in the centre of the hepatic acinus.read more
Citations
More filters
Journal ArticleDOI
The role of glutathione in chloroform-induced hepatotoxicity.
E.L. Docks,Gopal Krishna +1 more
TL;DR: Chloroform administered to phenobarbital-pretreated rats decreased liver glutathione (GSH) and caused massive liver necrosis and it appeared that depletion was related to CHCl3 metabolism.
Journal ArticleDOI
Chemically induced nephrotoxicity: role of metabolic activation.
TL;DR: Renal xenobiotic metabolism can result in production of electrophiles or free radicals that may covalently bind macromolecules or initiate lipid peroxidation in renal cells due to tubular concentrating and/or secretory mechanisms.
Journal ArticleDOI
Metabolism of haloforms to carbon monoxide—III: Studies on the mechanism of the reaction
J. L. Stevens,M. W. Anders +1 more
TL;DR: Results suggest an initial oxygen insertion reaction to yield a hydroxydihalomethane intermediate which would be expected to rearrange toield a formyl halide intermediate.
Journal ArticleDOI
Hepatotoxicity and halothane metabolism in an animal model with application for human toxicity.
Michael J. Cousins,J. H. Sharp,Geoffrey K. Gourlay,J. F. Adams,J. F. Adams,W. D. Haynes,R. Whitehead +6 more
TL;DR: It appears that a model with a similar route and rate of halothane biotransformation to man has been identified, and the lesion ofHalothane hepatotoxicity in this model appears to be similar to that reported in man — centrilobular hepatic necrosis.
Journal ArticleDOI
Acute alteration of chloroform-induced hepato- and nephrotoxicity by n-hexane, methyl n-butyl ketone, and 2,5-hexanedione☆☆☆
TL;DR: The concept that ketones increase the susceptibility of animals to the toxic effects of haloalkanes is supported, as the ability to potentiate CHCl3-induced liver injury increased in the order of H < A < 2,5-HD ≅ MBK.
References
More filters
Journal ArticleDOI
Halothane biotransformation in man: a quantitative study.
TL;DR: The metabolic breakdown of Halothane was quantiatively determined in two patients and the least amount of halothane that had been metabolized was calculated on the basis of the excreted trifluoroacetic acid: 12 per cent in both patients.
Journal ArticleDOI
Role of the sympathetic nervous system in CCl4 hepatotoxicity
TL;DR: Adrenergic blocking agents, pretreatment with reserpine, adrenalectomy and section of the spinal cord are effective to a greater or lesser extent in preventing the changes characteristically seen in oxidative phosphorylation of the liver mitochondria, activation of a Mg-dependent ATPase and deposition of lipid in the liver.
Journal ArticleDOI
Metabolism of volatile anesthetics.
Journal ArticleDOI
Lipid metabolites of carbon tetrachloride
TL;DR: The evidence strongly suggests the formation of these metabolites by free radical attack on unsaturated lipids, probably containing the trichloromethyl side chain, in rats of (14)C- or (36)Cl-carbon tetrachloride intoxication.
Journal ArticleDOI
Inhibition of drug demethylation by disulfiram in vivo and in vitro
T. Honjo,K. J. Netter +1 more