Bioactivation of Morphine in Human Liver : Isolation and Identification of Morphinone, a Toxic Metabolite(Miscellaneous)
スポンサーリンク
概要
- 論文の詳細を見る
Morphinone, identified in the bile of guinea pigs and rats given morphine, is a reactive electrophile and has the ability to bind to glutathione (GSH) and tissue macromolecules, leading to GSH depletion and cell damage. We previously demonstrated that the livers of various animal species are capable of forming morphinone from morphine. In this study, we examined whether the human liver can produce morphinone from morphine. HPLC analysis revealed that the incubation of morphine with the 9000×g supernatant of human liver in the presence of NAD(P) and 2-mercaptoethanol (ME) gave a peak corresponding to the synthetic morphinone-ME adduct (MO-ME), which is readily formed by a nonenzymatic reaction of morphinone with ME. The reaction product was isolated and was unambiguously identified as MO-ME using FAB-MS and NMR analyses in comparison with synthetic MO-ME. The conversion of morphine to morphinone required NAD(P), and NAD was a preferred cofactor over NADP. All the 9000×g supernatants from six human livers could produce morphinone at different rates, ranging from 30 to 120nmol/g liver/30min with NAD at pH 7.4. The enzyme activity responsible for the formation of morphinone from morphine was mainly localized in the microsomes. The microsomal enzyme activity was inhibited by steroids, lithocholic acid and indomethacin. Among these compounds, steroids with a 17β-hydroxyl group almost completely depressed morphinone formation. In conclusion, the metabolic pathway of morphine to morphinone, a toxic metabolite, in human was shown for the first time in in vitro experiments.
- 公益社団法人日本薬学会の論文
- 2005-07-01
著者
-
ISHIDA Takashi
Faculty of Science,Osaka University
-
NARIMATSU Shizuo
Faculty of Pharmaceutical Sciences, Okayama University
-
Yamano Shigeru
Faculty of Pharmaceutical Sciences, Fukuoka University
-
Kita Hideki
Faculty of Pharmaceutical Sciences, Fukuoka University
-
Kita Hideki
Faculty Of Pharmaceutical Sciences Fukuoka University
-
Todaka Takashi
Faculty Of Engineering Oita University
-
Narimatsu Shizuo
Faculty Of Pharmaceutical Sciences Okayama University
-
Todaka Takashi
Faculty Of Pharmaceutical Sciences Fukuoka University
-
Yamano S
Faculty Of Pharmaceutical Sciences Fukuoka University
-
Yamano Shigeru
Faculty Of Pharmaceutical Sciences Fukuoka University
-
Ishida Takashi
Faculty Of Pharmaceutical Sciences Fukuoka University
-
Yamano Shigeru
Faculty of Pharmaceutical Science, Fukuoka University
関連論文
- de Haas-van Alphen Oscillation in the Superconducting Mixed State of URu_2Si_2
- Two-Electron Quinone Reductase (Aldo-keto Reductase 1C Isozyme) Augments the Oxidative DNA Damage Induced by Quinones in Diesel Exhaust Particles by Accelerating Redox Cycling
- Identificaiton and Characterization of the sodA Genes Encoding Manganese Superoxide Dismutases in Vibrio parahaemolyticus, Vibrio mimicus, and Vibrio vulnificus
- Characterization of Vibrio parahaemolyticus Manganese-Resistant Mutants in Reference to the Function of the Ferric Uptake Regulatory Protein
- Cloning and Characterization of the ddc Homolog Encoding L-2,4-Diaminobutyrate Decarboxylase in Enterbacter aerogenes
- Siderophore Production of Vibrio parahaemolyticus Strains from Different Sources
- Determination of N-Ethylglycine in Urine of Cancer Patients with Metastatic Bone Disease by HPLC Using 4-(5,6-Dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl Chloride as a Fluorescent Labeling Reagent
- Single Crystal Growth and the Upper Critical Field of the Superconductor U_6Fe
- de Haas-van Alphen Oscillation in Both Normal and Superconducting Mixed States of CeRu_2
- Mechanism of Hepatic Microsomal Oxidation of 11-Hydroxy-Δ^8-tetra-hydrocannabinol to 11-Oxo-Δ^8-tetrahydrocannabinol. Evidence for Hydration of the Aldehyde Formed
- INTERACTION OF CANNABINOIDS WITH HEPATIC MICROSOMAL DRUG-METABOLIZING ENZYME SYSTEM IN THE RAT
- Study of the Counterclockwise/Clockwise (CCW/CW) Rotational Losses Measured with a Two-dimensional Vector Magnetic Property Measurement System
- Development of High-Density Electrical Machines(Special Issue of the Asia-Pacific Symposium on Applied Electromagnetics and Mechanics (APSAEM06))
- Development of Iron-based ferromagnetic shape memory alloys by means of melt spinning technique
- Development of High Density and High Efficiency Machines
- Evaluation of Stress Loaded Steel Samples Using Electromagnetic Method
- Purification and Characterization of Two Major Forms of Naloxone Reductase from Rabbit Liver Cytosol, New Members of Aldo-Keto Reductase Superfamily
- DECREASED URINARY EXCRETION OF THIAMINE PROPYL DISULFIDE METABOLITES IN PATIENTS WITH LIVER DISEASE
- DETERMINATION OF URINARY METABOLITES OF THIAMINE PROPYL DISULFIDE IN HUMANS
- Bioactivation of Morphine in Human Liver : Isolation and Identification of Morphinone, a Toxic Metabolite(Miscellaneous)
- STIMULATION OF NALOXONE AND MORPHINE METABOLISM IN GUINEA PIG
- EFFECTS OF A VARIETY OF COMPOUNDS ON THE BILIARY EXCRETION OF MORPHINONE AND MORPHINONE-GLUTATHIONE ADDUCT
- PRODUCTION OF MORPHINONE BY IN VITRO METABOLISM OF MORPHINE
- ALTERED THIAMINE PROPYL DISULFIDE METABOLISM IN RATS WITH LIVER INJURY INDUCED BY CARBON TETRACHLORIDE AND D-GALACTOSAMINE
- PROBLEMS OF RESEARCH WORK ON GUINEA PIG LIVER MORPHINE 6-DEHYDROGENASE
- Application of rotational Barkhausen Noise evaluation method in estimation of residual stress (特集 第16回MAGADAコンファレンス)
- Evaluation of Barkhausen noise parameters selected in variable excitation signal frequency and amplitude conditions with special consideration of sine and pulse excitation schemes (特集 第15回MAGDAコンファレンス)
- Siderophore-Mediated Utilization of Transferrin- and Lactoferrin-Bound Iron by Acinetobacter baumannii
- Determination of daidzein and genistein in soybean foods by automated on-line in-tube solid-phase microextraction coupled to high-performance liquid chromatography
- Uniform-Sized Molecularly Imprinted Polymer Material for Propranolol. Recognition of Propranolol and Its Metabolites
- METABOLISM AND TOXICITY OF MORPHINE RELATED COMPOUNDS
- MORPHINE METABOLISM AND A POSSIBLE MECHANISM OF THE DEVELOPMENT OF TOLERANCE
- THE COMPARISON OF THE EFFECTS OF MORPHINONE AND NALOXONE ON THE ANALGESIC ACTIVITY AND ACUTE TOXICITY OF MORPHINE BY INTRACEREBRAL INJECTION
- TOXICITY OF MORPHINONE AND EFFECTS OF MORPHINONE ON THE ANALGESIC ACTIVITY OF MORPHINE
- DETERMINATION OF OXYCODONE METABOLITES IN URINES AND FECES OF SEVERAL MAMMALIAN SPECIES
- A NOVEL METABOLITE OF OXYCODONE IN THE URINE OF RABBITS
- Magnetic Property Distribution in a Magnetic Circuit Model Core Measured with a Very Small Two-dimensional Vector Magnetic Sensor (特集 The 20th MAGDA Conference in Pacific Asia (MAGDA2011))
- Distributions of Local Vector Magnetic Property in a Three-phase Induction Motor Model Core by Using a Small-sized Vector Hysteresis Sensor (特集 The 20th MAGDA Conference in Pacific Asia (MAGDA2011))
- Magnetic Property Distribution in a Magnetic Circuit Model Core Measured with a Very Small Two-dimensional Vector Magnetic Sensor(The 20th MAGDA Conference in Pacific Asia (MAGDA2011))
- Distributions of Local Vector Magnetic Property in a Three-phase Induction Motor Model Core by Using a Small-sized Vector Hysteresis Sensor(The 20th MAGDA Conference in Pacific Asia (MAGDA2011))
- Expression of Hepatic Fat-Specific Protein 27 Depends on the Specific Etiology of Fatty Liver