Biomaterial Database

Effect of volatile anesthetics on the hepatic UDP-glucuronic acid pathway in mice. 1990

J B Watkins, and D R Engles, and L V Beck

Pharmacology Section, Indiana University School of Medicine, Bloomington 47405.

Large, rapid decreases in hepatic UDP-glucuronic acid concentrations occur in rats following exposure to myriad chemicals. In fact, 80% reductions in UDP-glucuronic acid occur within minutes after exposure to inhalation anesthetics. The present study was designed to determine whether this decrease in hepatic UDP-glucuronic acid may be due to (a) a decrease in the precursor UDP-glucose; (b) decreased activity of UDP-glucose dehydrogenase, which oxidizes UDP-glucose to UDP-glucuronic acid; (c) increased activity of UDP-glucuronosyltransferases; or (d) increased activity of nucleotide pryophosphatase, which degrades UDP-glucuronic acid to glucuronic acid-1-phosphate. Exposure to halothane, isoflurane and sevoflurane decreased UDP-glucuronic acid concentrations by 40-52% as compared to that in unanesthetized control mice. No sex-dependent or anesthetic-induced effects of UDP-glucose levels and the activities of UDP-glucose dehydrogenase and UDP-glucuronosyltransferase were observed. Nucleotide pyrophosphatase activity was increased by 47-65% in female mice after inhalation of halothane, isoflurane and sevoflurane. The apparent Vmax for hydrolysis of 4-nitrophenol thymidine 5'-monophosphate ester by nucleotide pyrophosphatase was increased by 56-80% in female mice, whereas the apparent Km was unchanged. These alterations in nucleotide pyrophosphate kinetics may be responsible, in part, for the marked decrease of hepatic UDP-glucuronic acid concentrations by the volatile anesthetics.

UI	MeSH Term	Description	Entries
D007530	Isoflurane	A stable, non-explosive inhalation anesthetic, relatively free from significant side effects.
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
D008738	Methyl Ethers	A group of compounds that contain the general formula R-OCH3.	Ethers, Methyl
D011755	Pyrophosphatases	A group of enzymes within the class EC 3.6.1.- that catalyze the hydrolysis of diphosphate bonds, chiefly in nucleoside di- and triphosphates. They may liberate either a mono- or diphosphate. EC 3.6.1.-.	Pyrophosphatase
D004987	Ethers	Organic compounds having two alkyl or aryl groups bonded to an oxygen atom, as in the formula R1–O–R2.
D005260	Female		Females
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
D000077149	Sevoflurane	A non-explosive inhalation anesthetic used in the induction and maintenance of general anesthesia. It does not cause respiratory irritation and may also prevent PLATELET AGGREGATION.	BAX 3084,Fluoromethyl Hexafluoroisopropyl Ether,Fluoromethyl-2,2,2-trifluoro-1-(trifluoromethyl)ethyl Ether,Sevorane,Ultane
D000777	Anesthetics	Agents capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general ANESTHESIA, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site.	Anesthetic,Anesthetic Agents,Anesthetic Drugs,Anesthetic Effect,Anesthetic Effects,Agents, Anesthetic,Drugs, Anesthetic,Effect, Anesthetic,Effects, Anesthetic