Biomaterial Database

The role of oxidative biotransformation of halothane in the guinea pig model of halothane-associated hepatotoxicity. 1989

R C Lind, and A J Gandolfi, and P D Hall

Department of Pathology, Flinders Medical Centre, Bedford Park.

The role of the oxidative pathway of halothane biotransformation in mediating the hepatotoxicity of halothane in the guinea pig was examined by utilizing the deuterated form of halothane (d-halothane), which is resistant to oxidative metabolism. Male outbred Hartley guinea pigs were exposed to either 1% v/v halothane or d-halothane, FIO2 = 0.21, for 4 h. Significant reductions in both oxidative and overall halothane biotransformation were observed with the use of d-halothane as indicated by decreased plasma levels of trifluoroacetic acid and bromide ion, respectively, immediately following exposure. Plasma fluoride ion, indicative of the reductive metabolism of halothane, was significantly increased with the use of d-halothane. These changes in metabolism were accompanied by a reduced hepatotoxic response as indicated by significantly decreased plasma ALT levels 24-96 h following exposure and a significantly lesser incidence of centrilobular necrosis. Thus, the oxidative biotransformation of halothane is implicated as a mechanism of injury in guinea pigs.

UI	MeSH Term	Description	Entries
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
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
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
D001711	Biotransformation	The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
D056486	Chemical and Drug Induced Liver Injury	A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, herbal and dietary supplements and chemicals from the environment.	Drug-Induced Liver Injury,Liver Injury, Drug-Induced,Acute Liver Injury, Drug-Induced,Chemically-Induced Liver Toxicity,Drug-Induced Acute Liver Injury,Drug-Induced Liver Disease,Hepatitis, Drug-Induced,Hepatitis, Toxic,Liver Injury, Drug-Induced, Acute,Toxic Hepatitis,Acute Liver Injury, Drug Induced,Chemically Induced Liver Toxicity,Chemically-Induced Liver Toxicities,Disease, Drug-Induced Liver,Diseases, Drug-Induced Liver,Drug Induced Acute Liver Injury,Drug Induced Liver Disease,Drug Induced Liver Injury,Drug-Induced Hepatitides,Drug-Induced Hepatitis,Drug-Induced Liver Diseases,Drug-Induced Liver Injuries,Hepatitides, Drug-Induced,Hepatitides, Toxic,Hepatitis, Drug Induced,Injuries, Drug-Induced Liver,Injury, Drug-Induced Liver,Liver Disease, Drug-Induced,Liver Diseases, Drug-Induced,Liver Injuries, Drug-Induced,Liver Injury, Drug Induced,Liver Toxicities, Chemically-Induced,Liver Toxicity, Chemically-Induced,Toxic Hepatitides,Toxicities, Chemically-Induced Liver,Toxicity, Chemically-Induced Liver