Biomaterial Database

Bioactivation and covalent binding of halothane in vitro: studies with [3H]- and [14C]halothane. 1980

A J Gandolfi, and R D White, and I G Sipes, and L R Pohl

To determine if the hydrogen atom of halothane (CF3CHBrCl) is retained on the reactive intermediates that covalently bind to microsomal lipids and protein, [3H]halothane and [14C]halothane were incubated with rat hepatic microsomes and a NADPH generating system. Both [3H]- and [14C]halothane were bioactivated and bound to a greater degree when incubations were performed in a N2 atmosphere rather than an O2 atmosphere. Binding of [3H]- and [14C]halothane equivalents was significanty enhanced when heaptic microsomes from phenobarbital- or Aroclor 1254-treated rats were used in the incubations. Omission of NADPH or incubation with CO was inhibitory to the binding of both [3H]- and [14C]halothane. The apparent kinetic constants for binding or halothane equivalents, Km and Vmax, indicate a significantly higher Km but lower Vmax for the formation and/or binding of 3H-binding equivalents. The results indicate tht halothane is primarily bioactivated under conditions that promote its reductive metabolism and that this reactive metabolism does not involve cleavage of the carbon-hydrogen bond of halothane. Differences in binding under N2 and O2 as well as between [3H]- and [14C]halothane suggest that multiple reactive intermediates may form during the biotransformation of halothane.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D008862	Microsomes, Liver	Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.	Liver Microsomes,Liver Microsome,Microsome, Liver
D009584	Nitrogen	An element with the atomic symbol N, atomic number 7, and atomic weight [14.00643; 14.00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells.
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
D002250	Carbon Radioisotopes	Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.	Radioisotopes, Carbon
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.
D014316	Tritium	The radioactive isotope of hydrogen also known as hydrogen-3. It contains two NEUTRONS and one PROTON in its nucleus and decays to produce low energy BETA PARTICLES.	Hydrogen-3,Hydrogen 3