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.
Aldehyde Oxidase ; Aminopyrine N-Demethylase ; Aniline Compounds ; Aniline Hydroxylase ; Animals ; Antioxidants ; Catalase ; Cisplatin ; Creatinine ; Cyclooctanes ; Glutathione ; Glutathione Peroxidase ; Glutathione Transferase ; Kidney ; L-Lactate Dehydrogenase ; Lignans ; Lipofuscin ; Peroxidase ; Polycyclic Compounds ; Rats ; Reactive Oxygen Species ; Renal Insufficiency ; Selenium ; Superoxide Dismutase ; Xanthine Oxidase

OBJECTIVETo 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.

METHODThe activities of phase II enzymes (GSH-related enzymes) and cytochrome P450 enzymes were measured by biochemical method.

RESULTASP 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.

CONCLUSIONASP can modulate the activities of drug metabolism enzymes.

Aminopyrine N-Demethylase ; metabolism ; Angelica sinensis ; chemistry ; Aniline Hydroxylase ; metabolism ; Animals ; Chemical and Drug Induced Liver Injury ; enzymology ; etiology ; Cytochrome P-450 Enzyme System ; metabolism ; Glutathione Transferase ; metabolism ; Male ; Mice ; Microsomes, Liver ; enzymology ; Mitochondria, Liver ; enzymology ; NADPH-Ferrihemoprotein Reductase ; metabolism ; Plants, Medicinal ; chemistry ; Polysaccharides ; isolation & purification ; pharmacology ; Prednisolone

OBJECTIVETo investigate the effects of the ethyl acetate extract of Semen Hoveniae (ESH) on liver microsomal cytochrome P450 isoenzyme in rats.

METHODThe 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).

RESULTThe 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.

CONCLUSIONA 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.

Acetates ; chemistry ; Aminopyrine N-Demethylase ; metabolism ; Aniline Hydroxylase ; genetics ; metabolism ; Animals ; 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 ; isolation & purification ; pharmacology ; Gene Expression Regulation, Enzymologic ; drug effects ; Male ; Microsomes, Liver ; drug effects ; enzymology ; NADPH-Ferrihemoprotein Reductase ; genetics ; metabolism ; Plants, Medicinal ; chemistry ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Rhamnaceae ; chemistry ; Seeds ; chemistry ; Steroid 16-alpha-Hydroxylase ; genetics ; metabolism

This paper is aimed to study the metabolic kinetics of nicousamide in rat liver microsomes and cytosol and to identify the major metabolite and drug metabolizing enzymes involved in the metabolism of nicousamide in rat and human liver microsomes by selective inhibitors in vitro. The concentration of nicousamide was determined by HPLC-UV method. The metabolite of nicousamide in rat and human liver microsomes was isolated and identified by LC-MS/MS. The major metabolite of nicousamide in rat and human liver microsomes was identified to be 3-(3'-carboxy-4'-hydroxy-anilino-carbo-)-6-amino-7-hydroxy-8-methyl-coumarin (M1). The metabolite of nicousamide in rat plasma, urine, bile and liver was consistent with M1. The metabolism of nicousamide can be catalyzed by several reductases, including CYP450 reductases, cytochrome b5 reductases and CYP2C6 in rat liver microsomes, as well as xanthine oxidase and DT-diaphorase in rat liver cytosol.
Adenosine Monophosphate ; pharmacology ; Allopurinol ; pharmacology ; Aniline Compounds ; metabolism ; Animals ; Cimetidine ; pharmacology ; Coumarins ; metabolism ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P450 Family 2 ; Cytochrome-B(5) Reductase ; antagonists & inhibitors ; Cytosol ; metabolism ; Dicumarol ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Female ; Humans ; Liver ; cytology ; metabolism ; Male ; Microsomes, Liver ; metabolism ; Mitochondria, Liver ; metabolism ; NAD(P)H Dehydrogenase (Quinone) ; antagonists & inhibitors ; Propylthiouracil ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Steroid 21-Hydroxylase ; antagonists & inhibitors ; Xanthine Oxidase ; antagonists & inhibitors