Effect of adlay bran ethanolic extract on drug metabolism and oxidative stress in rats
| Autor: | Jia-Hsuan Lin, 林佳璇 |
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| Rok vydání: | 2010 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 98 Studies have shown that adlay（Coix lachrymal-jobi L.var. mayuen Stapf） has beneficial effects on the prevention of many diseases. The lipopholic components of adlay bran have been demonstrated to have plasma lipids-lowering effects and reduce carcinogenesis in colon and lung cancer cell lines. To investigate whether the adlay bran ethanolic extract (ABE) can cause drug interactions and to evaluate the long-term administration of ABE on drug-metabolizing enzymes and oxidative stress in tissues, three experiments were conducted. Experiment I: HPLC/MS system was used to identify the components in ABE. The inhibitory effect of ABE on CYP enzymes activities in rat and human liver microsomes were determined. In addition, the effect of single oral dose of ABE on the pharmacokinetics of five CYP probe drugs (CYP1A2: theophylline, CYP2C: diclofenac, CYP2D: dextromethophen, CYP2E1: chlorzoxazone and CYP3A: dilitiazem) administered orally or intravenously in rats were also evaluated. Experiment II: This study was to evaluate the short-term administration (20% ABE in the diet for 10 days) of ABE on the pharmacokinetics of five CYP probe drugs and the modulations of ABE on CYP enzymes in liver. Experiment III: This study was to understand the long-term administration (5 and 10% ABE in the diet for 4 weeks) of ABE on drug-metabolizing enzymes and oxidative stress in liver, kidney and lung tissues. Results show that 16 phenolic compounds and 3 phytosterols were identified in ABE. ABE inhibited CYP3A, 2C, 2D, 2E1 and 1A1 enzyme activities in both rat (IC50: 18.0-57.4 μg/mL) and human (IC50: 15.4-44.8 μg/mL) liver microsomes. However, ABE showed relative weak inhibition (IC50>100 μg/mL) on CYP1A2 activity in both rat and human liver microsomes. ABE increased the area under the curve (AUC) of plasma theophylline and dextromethorphan when co-administrated orally but not intravenously with five CYP probe drugs, indicating the drug interactions might be occurred in the small intestine. Furthermore, rats were fed with 20% ABE for 7 days increased the AUC of plasma theophylline and chlorzoxazone and the hepatic CYP2C enzyme activity and protein levels were reduced after 10 days of ABE treatment. Finally, rats fed the ABE-containing diets for 4 weeks reduced CYP3A, 2C, 2D and 1A1 enzyme activities and protein levels in liver and decreased CYP1A1 enzyme activity and protein level in lung. Moreover, higher GSH level, GSH/GSSG ratio, GSH-Px, GSH-Rx and GST activities and NQO-1 protein levels were noted in lung after the ABE treatment. Results from our data indicate that ABE can inhibit several CYP enzymes activities in the liver and this impact is prominent after long-term ABE administration. When co-administrated with certain drugs, ABE may increase systemic drugs exposure and this effect may be also changed by the duration of ABE treatment. Long-term administration of ABE may reduce hepatic CYP enzymes and oxidative stress in lung. |
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