Biomaterial Database

Halothane hepatotoxicity in hyperthyroid rats as compared to the phenobarbital-hypoxia model. 1983

C P Siegers, and A Frühling, and M Younes

Halothane hepatotoxicity was observed after exposing hyperthyroid rats to 0.625% halothane for 4 hr under hypoxic conditions (10% O2). In this model, increases in serum enzyme activities of the alanine aminotransferase (GPT) and the sorbitol dehydrogenase (SDH) were evident immediately following exposure and were six-fold higher than in the phenobarbital-hypoxic model. Plasma free-fluoride levels estimated immediately after exposure to halothane were increased twofold in halothane-exposed hyperthyroid rats under hypoxic conditions as were increased twofold in halothane-exposed hyperthyroid rats under hypoxic conditions as compared to a sixfold increase in the phenobarbital-hypoxic model. The concentration of glutathione in liver was more markedly decreased in hyperthyroid rats than in phenobarbital-induced rats. The fact that no clear-cut correlation was found between defluorination and hepatotoxicity in both models may favor the hypothesis that a non-defluorinated metabolite of halothane, e.g., 2-chloro-1,1,1-trifluoroethyl radical, is the reactive intermediate responsible for the liver lesions. On the other hand, intracellular hypoxia due to hypermetabolism during the hyperthyroid state may be the reason for the higher sensitivity of hyperthyroid rats.

UI	MeSH Term	Description	Entries
D006980	Hyperthyroidism	Hypersecretion of THYROID HORMONES from the THYROID GLAND. Elevated levels of thyroid hormones increase BASAL METABOLIC RATE.	Hyperthyroid,Primary Hyperthyroidism,Hyperthyroidism, Primary,Hyperthyroids
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
D008297	Male		Males
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
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
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D005459	Fluorides	Inorganic salts of hydrofluoric acid, HF, in which the fluorine atom is in the -1 oxidation state. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Sodium and stannous salts are commonly used in dentifrices.	Fluoride
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
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