title: The influence of anesthetic concentrations of enflurane and ethanol on caffeine metabolism in mice.
abstract: Enflurane is a fluorinated volatile anesthetic, mostly eliminated unchanged in exhaled air. About 10% of inhaled enflurane undergoes oxidative metabolism in liver via mixed function oxidase. We examined the influence of ethanol and subchronical exposition (6 hours a day, during five consecutive days) to subanesthetic and anesthetic concentrations of enflurane on liver function in BALB/c mice. Specially designed chamber for inhalatory application of anesthetics was constructed for this study. Animals were divided in six groups of twenty. The ethanol treated group was injected with ethanol intraperitoneally (1 g/kg). Two enflurane treated groups were intraperitoneally injected with 0.9% solution of sodium chloride (10 ml/kg) and one of them exposed to subanesthetic (0.5 Vol%) and the other one to anesthetic (2.75 Vol%) concentrations of enflurane. Following two groups received ethanol (1 g/kg) and each of them inhaled enflurane at previously mentioned doses. The control group was intraperitoneally injected with 0.9 % solution of sodium chloride (10 ml/kg) and did not receive any anesthetic. On the day following the last day of exposure half of the animals from each group were sacrificed for determination of glucose levels, erythrocyte glutathion levels, haematocrit, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), liver protein and glutathion levels, and total cytochrome P-450 (CYP P-450). The other half of animals from each group were injected intraperitoneally with caffeine (20 mg/kg). Caffeine and its metabolites in 8 hour urine were analyzed by high performance liquid chromatography (HPLC) method. Excretion of caffeine and its metabolites was different among the groups. We followed two caffeine metabolic ratios - 1,3-dimethyl uric acid and 3,7-xanthine (1,3-U/3,7-X) and 3,7-dimethyl xanthine + 7-xanthine and 1-xanthine + 1,7-dimethyl uric acid (3,7-X + 7-X/1-X + 1,7-U). The difference in caffeine metabolites ratios suggests that enflurane changes oxidative metabolism in liver via certain subtypes of mixed function oxidase, probably via CYP-4502E1. This effect is more expressed when ethanol and enflurane are applied together. Ethanol is well known inductor of CYP-4502E1 and the registrated enzyme induction could be explained by both influences - of ethanol and enflurane.
authors.affiliation: Institute for Child and Youth Health Care, Department of Pediatric Hematology/Oncology, Novi Sad, FR Yugoslavia.
authors.forename: J
authors.initials: J
authors.lastname: Kolarović
authors.forename: M
authors.initials: M
authors.lastname: Mikov
authors.forename: V
authors.initials: V
authors.lastname: Ristovski
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002110:Caffeine / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004737:Enflurane / Q000008:administration & dosage* / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D006400:Hematocrit; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D018685:Anesthetics, Inhalation; D001786:Blood Glucose; D002110:Caffeine; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D004737:Enflurane; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione