Effects Of Clausenamide, Tetrahydrocoptisine And Acepiperonethamine On Hepatic Drug Metabolizing Enzymes And Their Biological Consequences

Hepatic drug metabolizing enzymes include Phase I enzyme (Cytochrome P-450 ) and Phase II enzyme ( mainly UDPG-T and GSH-S-T ) . Detoxication is a result of sequential action of enzymes both phases. In certain cases, some drugs, toxicants and carcinogens are metabolized by liver microsomal cytochrome P-4 50 to reactive metabolites which covalently bind to cell macromolecules, such as DNA, RNA and protein. This process is called intoxication. Under the catalysis of Phase II enzymes, most of the reactive metabolites can be detoxicated by forming conjugates of glycuronic acid, GSH, and so on. Therefore, the functional state of drug metabolizing enzymes is an important determinant for drug activity as well as toxicity.Clausenamide (Claus ) and Tetrahydrocoptisine ( THC ) are alkaloids isolated from leaves of Clausena Lausium ( cour ) Skeels and Chelidonium Majus L. , respectively. Acepiperonethamine ( APE ) was chemically synthesized. Our past investigations demonstrated that the three compounds have protective actions against experimental liver injuries induced by hepatotoxins and have inductive effect on hepatic microsomal cytochrome P-450 in mice. In this dissertation, further investigations of the effects of the three compounds on hepatic cytochrome P-450, UDPG-T and GSH-S-T activities were performed. In order to analyze the relationship between the functional state of liver drug metabolizing enzymes and toxicity of several toxicants under the influence of the three compounds, the effects of Claus, THC and APE on the metabolism and toxicity of N-acetyl-p-aminophenol ( APAP), Benzo(a)pyrene ( BP ) and Aflatoxin B1 ( AFB1 ) were also studied.The results indicate that the liver microsomal benzophentamine-N-demethylase activity was obviously inhibited 2 hours after administration of Claus 250 mg/kg, THC 250 mg/kg or APE 150 mg/kg in mice while the...