Cytotoxicity of i.v. anaesthetic agents on the isolated rat hepatocyte. 1979

J W Sear, and J D McGivan

The isolated rat hepatocyte model has been used to assess the hepatotoxicity of a number of i.v. anaesthetic induction agents. Ketamine, Althesin and CCI 12923 (minaxolone) all inhibited gluconeogenesis and urea formation from alanine. There was also a decrease in the cell ATP concentration, and a dose-related increase in leakage of LDH. Of these indices of cell toxicity, gluconeogenesis from alanine was found to be the most sensitive. Fifty per cent inhibition of gluconeogenesis for all three agents occurred in the range 150--300 mumol. The effects of these agents on the isolated hepatocyte may be attributed to a primary impairment of mitochondrial function through a change in the ATP concentration. The plasma concentration of anaesthetic agents measured during their clinical use is at least one order of magnitude less than that required to cause 50% inhibition of gluconeogenesis.

UI MeSH Term Description Entries
D007649 Ketamine A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors. 2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone,CI-581,Calipsol,Calypsol,Kalipsol,Ketalar,Ketamine Hydrochloride,Ketanest,Ketaset,CI 581,CI581
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
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003864 Depression, Chemical The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical. Chemical Depression,Chemical Depressions,Depressions, Chemical
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005943 Gluconeogenesis Biosynthesis of GLUCOSE from nonhexose or non-carbohydrate precursors, such as LACTATE; PYRUVATE; ALANINE; and GLYCEROL.
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000530 Alfaxalone Alfadolone Mixture A 3:1 mixture of alfaxalone with alfadolone acetate that previously had been used as a general anesthetic. It is no longer actively marketed. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1445) Alfatesine,Alfathesin,Alphadione,Alphathesin,Althesin,CT-1341,Glaxovet,Saffan,Alfadolone Mixture, Alfaxalone,CT 1341,CT1341

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