ABSTRACT
PURPOSE: This study investigated the effect of reducing cisplatin induced nephrotoxicity with DWP-04 that is the compound of Schizandrin C derivative biphenyldimethyl dicarboxylate (DDB), glutathione and selenium. For the purpose of observation is that how DWP-04 has influence on mechanism of reducing cisplatin induced nephrotoxicity with renal function test, free radical formation and detoxification enzyme system in renal tissue. METHODS: Five groups of rats were dosed with vehicle, cisplatin (2 mg/kg i.p.), cisplatin+DWP-04 (100, 200 mg/kg po), or cisplatin+sodium thiosulfate (200 mg/kg i.p.) daily for 4 weeks. RESULTS: Serum creatinine, lactate dehydrogenase and activity of hydroxy radical increased in the cisplatin group and suppressed in the cisplatin+DWP-04 group compared to the cisplatin group. The renal tissue concentration of lipid peroxidase and lipofuscin were increased in the cisplatin group compared to the other groups. The activity of aminopyrine N-demethylase, aniline hydroxylase, aldehyde oxidase and xanthine oxidase, of which free radical formation system in kidney was also decreased in the cisplatin+DWP-04 group compared to the cisplatin and cisplatin+sodium thiosulfate group. The activity of detoxification system of free radical, such as glutathione S-transferase, superoxide dismutase, catalase and glutathione peroxidase were markedly increased in the cisplatin+DWP-04 group than the cisplatin and the cisplatin+sodium thiosulfate group (p<0.05). CONCLUSION: It can be concluded that the mechanism of decreasing cisplatin-induced nephrotoxicity by DWP-04 is that the decreasing of the amount of lipid peroxide and lipofuscin in the renal tissue by increasing activity of the antioxidant defense system and the decreasing of reactive oxygen species by increasing detoxification enzyme activity.
Subject(s)
Animals , Rats , Aldehyde Oxidase , Aminopyrine N-Demethylase , Aniline Compounds , Aniline Hydroxylase , Antioxidants , Catalase , Cisplatin , Creatinine , Cyclooctanes , Glutathione , Glutathione Peroxidase , Glutathione Transferase , Kidney , L-Lactate Dehydrogenase , Lignans , Lipofuscin , Peroxidase , Polycyclic Compounds , Reactive Oxygen Species , Renal Insufficiency , Selenium , Superoxide Dismutase , Xanthine OxidaseABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of the ethyl acetate extract of Semen Hoveniae (ESH) on liver microsomal cytochrome P450 isoenzyme in rats.</p><p><b>METHOD</b>The rats were given orally the ESH in the doses of 0.14, 0.17, 0.2 g x kg (equivalent to the crude herb) for 10 days respectively. Rat liver microsomal cytochrome P450, NADPH-Cyt C reductase, erythromycin N-demethylase (ERD), Aniline hydroxylase (ANH), aminopyrine N-demethylase (ADM) activities were quantitated by UV chromatography. The levels of mRNA expression of CYP1A1, CYP2C11, CYP2E1 and CYP3A1 were detected by semi-quantitative reverse transcripatase-polymerase chain reaction (RT-PCR).</p><p><b>RESULT</b>The cytochrome P450 content, NADPH-Cyt C reductase activities and erythromycin N-demethylase (ERD) activities were not affected. Aniline hydroxylase (ANH) activities in liver were decreased by up to35.1%; aminopyrine N-demethylase (ADM) activitiesin liver were increased by up to 42.4%. The mRNA expression of CYP1A1, CYP2C11 and CYP3A1 were found to be increased markedly.</p><p><b>CONCLUSION</b>A specific effect of ESH on liver microsomal cytochrome P450 isoenzyme in rats was observed in this investigation. ESH had various effects on liver microsomal cytochrome P450 isoenzyme.</p>
Subject(s)
Animals , Male , Rats , Acetates , Chemistry , Aminopyrine N-Demethylase , Metabolism , Aniline Hydroxylase , Genetics , Metabolism , Aryl Hydrocarbon Hydroxylases , Genetics , Metabolism , Cytochrome P-450 CYP1A1 , Genetics , Metabolism , Cytochrome P-450 CYP2E1 , Genetics , Metabolism , Cytochrome P-450 CYP3A , Genetics , Metabolism , Cytochrome P-450 Enzyme System , Genetics , Metabolism , Cytochrome P450 Family 2 , Drugs, Chinese Herbal , Chemistry , Pharmacology , Gene Expression Regulation, Enzymologic , Microsomes, Liver , NADPH-Ferrihemoprotein Reductase , Genetics , Metabolism , Plants, Medicinal , Chemistry , RNA, Messenger , Genetics , Metabolism , Random Allocation , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Rhamnaceae , Chemistry , Seeds , Chemistry , Steroid 16-alpha-Hydroxylase , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To study the effects of Angelica sinensis Polysaccharides (ASP) on the hepatic drug metabolism enzymes activities in normal mice and those prednisolone (PSL)-induced liver injury.</p><p><b>METHOD</b>The activities of phase II enzymes (GSH-related enzymes) and cytochrome P450 enzymes were measured by biochemical method.</p><p><b>RESULT</b>ASP increased the activities of glutathione S-transferase in liver microsomes and mitochondria. The cytochrome P450 content, NADPH-cytochrome c reductase, aminopyrine N-demethylase, and aniline hydroxylase activities in liver microsomes were also increased. PSL significantly increased serum ALT levels, and decreased the liver mitochondrial glutathione content. At the same time, other enzymes activities were all increased. When mice were treated with ASP 2.0 g.kg-1, the PSL-induced changes on cytochrome P450 enzymes, glutathione S-transferase, and GSH content were restored.</p><p><b>CONCLUSION</b>ASP can modulate the activities of drug metabolism enzymes.</p>
Subject(s)
Animals , Male , Mice , Aminopyrine N-Demethylase , Metabolism , Angelica sinensis , Chemistry , Aniline Hydroxylase , Metabolism , Chemical and Drug Induced Liver Injury , Cytochrome P-450 Enzyme System , Metabolism , Glutathione Transferase , Metabolism , Microsomes, Liver , Mitochondria, Liver , NADPH-Ferrihemoprotein Reductase , Metabolism , Plants, Medicinal , Chemistry , Polysaccharides , Pharmacology , PrednisoloneABSTRACT
Trichloroethylene (TCE) is widely used as an industrial solvent and cleaning fluid. In the present study the toxic effects of TCE inhalation on pulmonary and hepatic biotransformation enzymes in rats have been investigated by assay of aniline hydroxylase (AH), aminopyrine-N-demethylase (APD), benzo-a-pyrene hydroxylase (BH) and glutathione-s-transferase (GST) activities and glutathione (GSH) contents in liver as well as lungs of exposed animals. In both organs phase I and phase II drug metabolizing enzymes have been found to be increased along with decrease in GSH contents following TCE inhalation. Pulmonary as well as hepatic MFO's seem to be activated by inhaled TCE probably in an attempt for its rapid detoxification and reduced glutathione is used during its biotransformation.
Subject(s)
Administration, Inhalation , Aminopyrine N-Demethylase/pharmacology , Aniline Hydroxylase/pharmacology , Animals , Benzopyrene Hydroxylase/pharmacology , Glutathione/analysis , Glutathione Transferase/pharmacology , Liver/drug effects , Lung/drug effects , Male , Rats , Rats, Wistar , Solvents/administration & dosage , Trichloroethylene/administration & dosageABSTRACT
Aniline hydroxylase from liver microsomes of rainbow trout Salmo gairdneri converted aniline to p-aminophenol, the specific activity being 0.068 nmoles/min/mg protein in potassium phosphate buffer, pH 7.4 at 25 degrees C. The maximal rate of the enzyme reaction was found at aniline concentrations above 5 mM and in the presence of NADPH. Vmax and K(m) were 0.048 nmoles/min/mg and 0.105 mM respectively. The Hill plot showed the Hill constant to be 1.02 indicating one substrate binding site with no cooperativity. Ca2+ and Mg2+ at concentrations ranging between 1-10 mM stimulated the enzyme activity.
Subject(s)
Aniline Hydroxylase/analysis , Animals , Microsomes, Liver/enzymology , Oncorhynchus mykissABSTRACT
Se desarrolló un modelo de diabetes experimental en ratas , analizaron los parámetros fisiológicos, el contenido de citocromo p-450 hepático y el metabolismo in vitro Fase I y II de estructuras moleculares modelos. Se observaron alteraciones significativas en el contenido de proteína microsomal hepática en las ratas diabéticas en tanto el tratamiento con insulina a estas ratas determinó una disminución del contenido de citocromo p-450 hepático. Las ratas diabéticas presentaron una capacidad metabólica in vitro Fase 1 mayor que las ratas controles y la administración de insulina produjo diversos efectos según sustrato empleado. El metabolismo in vitro Fase II de las ratas diabéticas resultó similar al obtenido en las ratas controles, en cambio el tratamiento con insulina produjo variaciones en la afinidad de la enzima por el sustrato y en la cantidad de la enzima que cataliza la reacción. Los resultados sugieren que el estado de diabetes y su tratamiento con insulina, modifica en forma diferente las isoenzimas citocromo P-450 y reduce selectivamente algunas enzimas UDP glucuronil transferasas.