Analysis of gene expression changes of drug metabolizing enzymes in the livers of F344 rats following oral treatment with kava extract
| Autor: | Lei Guo, Po Chuen Chan, Qingsu Xia, Peter P. Fu, Stacey L. Dial, Quan Zhen Li |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Microarray Pharmacology Toxicology Isozyme Gene Expression Regulation Enzymologic Article Cytochrome P-450 Enzyme System Gene expression Animals RNA Messenger Gene Kava Oligonucleotide Array Sequence Analysis chemistry.chemical_classification biology Dose-Response Relationship Drug Piper methysticum Plant Extracts Reverse Transcriptase Polymerase Chain Reaction Cytochrome P450 General Medicine Rats Inbred F344 Rats Enzyme chemistry Liver Dietary Supplements Inactivation Metabolic biology.protein Food Science |
| Zdroj: | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 47(2) |
| ISSN: | 1873-6351 |
| Popis: | The association of kava product use with liver-related risks has prompted regulatory action in many countries. We studied the changes in gene expression of drug metabolizing enzymes in the livers of Fischer 344 male rats administered kava extract by gavage for 14 weeks. Analysis of 22,226 genes revealed that there were 14, 41, 110, 386, and 916 genes significantly changed in the 0.125, 0.25, 0.5, 1.0, and 2.0 g/kg treatment groups, respectively. There were 16 drug metabolizing genes altered in all three high-dose treatment groups, among which seven genes belong to cytochrome P450 isozymes. While gene expression of Cyp1a1, 1a2, 2c6, 3a1, and 3a3 increased; Cyp 2c23 and 2c40 decreased, all in a dose-dependent manner. Real-time PCR analyses of several genes verified these results. Our results indicate that kava extract can significantly modulate drug metabolizing enzymes, particularly the CYP isozymes, which could cause herb-drug interactions and may potentially lead to hepatotoxicity. |
| Databáze: | OpenAIRE |
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