Biomaterial Database

Effect of classic and atypical neuroleptics on cytochrome P450 3A (CYP3A) in rat liver. 2012

Jacek Wójcikowski, and Anna Haduch, and Władysława A Daniel

Department of Pharmacokinetics and Drug Metabolism, Institute of Pharmacology, Polish Academy of Science, Smętna 12, PL 31-343 Kraków, Poland. wojcikow@if-pan.krakow.pl

BACKGROUND Cytochrome P450 3A (CYP3A) subfamily is involved in the metabolism of xenobiotics (e.g., drugs) and endogenous substances (e.g., steroids). The aim of the present study was to investigate the influence of classic and atypical neuroleptics on the level and activity of CYP3A in rat liver, measured as a rate of testosterone 2β- and 6β-hydroxylation. METHODS The reactions were studied in control liver microsomes in the presence of neuroleptics, as well as in the microsomes of rats treated intraperitoneally (ip) with pharmacological doses of the drugs (promazine and thioridazine 10 mg/kg; chlorpromazine 3 mg/kg; haloperidol 0.3 mg/kg; risperidone 0.1 mg/kg; sertindole 0.05 mg/kg) for one day or two weeks (twice a day), in the absence of the neuroleptics in vitro. RESULTS The investigated neuroleptics added in vitro to control liver microsomes produced a moderate or week inhibitory effects on CYP3A activity. After one-day exposure of rats to neuroleptics, only chlorpromazine significantly increased the activity of CYP3A. Chronic treatment of rats with thioridazine diminished the protein level and activity of CYP3A, while risperidone induced this enzyme. CONCLUSIONS The observed changes in the CYP3A expression after prolonged exposition to neuroleptics suggest their influence on the enzyme regulation.

UI	MeSH Term	Description	Entries
D007274	Injections, Intraperitoneal	Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.	Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D007527	Isoenzymes	Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.	Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D008565	Membrane Proteins	Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.	Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D008862	Microsomes, Liver	Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.	Liver Microsomes,Liver Microsome,Microsome, Liver
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006900	Hydroxylation	Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)	Hydroxylations