Dietary Diacetylene Falcarindiol Induces Phase 2 Drug-Metabolizing Enzymes and Blocks Carbon Tetrachloride-Induced Hepatotoxicity in Mice through Suppression of Lipid Peroxidation
スポンサーリンク
概要
- 論文の詳細を見る
Falcarindiol is a diacetylenic natural product containing unique carbon–carbon triple bonds. Mice were orally administrated falcarindiol (100 mg/kg), and drug-metabolizing and antioxidant enzymes were monitored in several tissues of mice. Treatment with falcarindiol was found to increase glutathione S-transferase (GST) and NAD(P)H: quinone oxidoreductase 1 activities in liver, small intestine, kidney, and lung. No changes were observed in cytochrome P450 (CYP) 1A known to activate procarcinogens. Western blot analysis revealed that various GST subunits including GSTA4, which plays an important role in the detoxification of alkenals produced from lipid peroxides, were induced in liver, small intestine, and kidney of falcarindiol-treated mice. Additionally, we investigated the protective effects of falcarindiol against hepatotoxicity induced by carbon tetrachloride (CCl4) and the mechanism of its hepatoprotective effect. Pretreatment with falcarindiol prior to the administration of CCl4 significantly suppressed both an increase in serum alanine transaminase/aspartate transaminase (ALT/AST) activity and an increase in hepatic thiobarbituric acid reactive substance levels without affecting CCl4-mediated degradation of CYP2E1. Formation of hexanoyl–lysine and 4-hydroxy-2(E)-nonenal–histidine adducts, lipid peroxidation biomarkers, in homogenates from the liver of CCl4-treated mice was decreased in the group of mice pretreated with falcarindiol. These results suggest that the protective effects of falcarindiol against CCl4 toxicity might, in part, be explained by anti-lipid peroxidation activity associated with the induction of the GSTs including GSTA4.
著者
-
NISHIYAMA TAKAHITO
Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Phar
-
Hiratsuka Akira
Department Of Biology Faculty Of Science Tohoku University
-
Ogura Kenichiro
Department Of Drug Metabolism And Molecular Toxicology School Of Pharmacy Tokyo University Of Pharma
-
Ohnuma Tomokazu
Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Phar
-
Anan Eisaburo
Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Phar
-
Hoashi Rika
Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Phar
-
Takeda Yuika
Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Phar
-
Nishiyama Takahito
Department Of Drug Metabolism And Molecular Toxicology School Of Pharmacy Tokyo University Of Pharma
-
Nishiyama Takahito
Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
-
Hoashi Rika
Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
-
Hiratsuka Akira
Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
-
Takeda Yuika
Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
関連論文
- Mechanism-Based Inactivation of Human Liver Microsomal CYP3A4 by Rutaecarpine and Limonin from Evodia Fruit Extract
- Sulfation of Environmental Estrogens by Cytosolic Human Sulfotransferases
- Formation of diconjugates from the phytoestrogen, genistein, in human liver.(GENERAL SESSION BY ORAL PRESENTATION)(DRUG METABOLISM)
- Rat and Mouse Liver Class Theta Glutathione S-Transferases Inactivating Reactive Metabolites Arylmethyl Sulfates (Proceedings of the 21st Symposium on Toxicology and Environmental Health)
- Characterization of The a Gene Encoding Rat Class Theta Glutathione S-Transferase Yrs
- RAT LIVER GLUTATHIONE S-TRANSFERASE Yrs-Yrs INACTIVATING REACTIVE SULFATE ESTERS AS METABOLITES OF CARCINOGENIC ARYLMETHANOLS
- "B-6 Accumulation of the toxic cholesterol 7-hydroperoxides in rat skin by aging and a glutathione-dependent reduction of the hydroperoxides.
- Inhibitory Effects of Herbal Extracts on the Activity of Human Sulfotransferase Isoform Sulfotransferase 1A3 (SULT1A3)(Biopharmacy)
- Reproductive Biology of an Amphicarpic Annual, Polygonum thunbergii (Polygonaceae) : Spatio-temporal Changes in Growth, Structure and Reproductive Components of a Population over an Environmental Gradient(US-JAPAN SEMINAR : EVOLUTIONARY STU
- A novel mouse liver glutathione S-transferase Μ4 inactivating arylmethyl sulfates as carcinogenic reactive metabolites
- Effects of Pretreatment of Hep G2 Cells with β-Naphthoflavone on Cytotoxicity of Propranolol and its Active Metabolite 4-Hydroxypropranolol
- Dietary Diacetylene Falcarindiol Induces Phase 2 Drug-Metabolizing Enzymes and Blocks Carbon Tetrachloride-Induced Hepatotoxicity in Mice through Suppression of Lipid Peroxidation
- Dog and monkey liver cytosolic phenol sulfotransferases : bacterial expression and characterization.
- Role of chloride anion in activation of mutagenic arylmethyl sulfates.
- SULFOTRANSFERASE-MEDIATED FORMATION OF DNA ADDUCTS WITH CARCINOGENIC ARYLMETHANOLS IN RAT LIVER
- METABOLIC ACTIVATION OF CARCINOGENIC ARYLMETHANOLS BY MICROHETEROGENEOUS RAT LIVER SULFOTRANSFERASES
- Production of High-Strength Glass-Ceramics from Industrial Wastes Using Phase Equilibrium Diagram of CaO-Al2O2-SiO2 System
- Regioselective Monosulfation and Disulfation of the Phytoestrogens Daidzein and Genistein by Human Liver Sulfotransferases
- Inhibitory Effects of Herbal Extracts on the Activity of Human Sulfotransferase Isoform Sulfotransferase 1A3 (SULT1A3)