Extrahepatic tissue distribution, covalent binding, and toxicity of halothane in control and phenobarbital-pretreated rats. 1978

G S Rao, and J O Grumley

Single anesthetic (11.5 mmole/kg) and nonanesthetic (4.6 mmole/kg) doses of 1-14C-halothane were administered separately to control and phenobarbital-pretreated rats by the intraperitoneal route. Tissue distribution and covalent binding of the anesthetic agent in the liver, lung, and kidney were determined at 4 and 24 hours after administration. Histopathological examination of the tissues revealed that halothane produced necrosis only in the livers of phenobarbital-pretreated rats and only after a period of 24 hours following the anesthetic dose. The lung and kidney appeared normal in all test animals. The liver was the major organ for the uptake, metabolism, and covalent binding of halothane metabolites to tissue proteins. Although similar metabolic activity was observed in the kidney and lung, toxic levels of the halothane metabolites were apparently not attained in these extrahepatic tissues in either control or phenobarbital-pretreated rats.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D009336 Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.
D010634 Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D006221 Halothane A nonflammable, halogenated, hydrocarbon anesthetic that provides relatively rapid induction with little or no excitement. Analgesia may not be adequate. NITROUS OXIDE is often given concomitantly. Because halothane may not produce sufficient muscle relaxation, supplemental neuromuscular blocking agents may be required. (From AMA Drug Evaluations Annual, 1994, p178) 1,1,1-Trifluoro-2-Chloro-2-Bromoethane,Fluothane,Ftorotan,Narcotan
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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