論文 - 詳細
| RRC ID | 63927 |
|---|---|
| 著者 | Taniguchi M, Miyamoto H, Tokunaga A, Fumoto S, Tanaka T, Nishida K. |
| タイトル | Evaluation of mRNA expression of drug-metabolizing enzymes in acetaminophen-induced hepatotoxicity using a three-dimensional hepatocyte culture system. |
| ジャーナル | Xenobiotica |
| Abstract |
1. The expression and activity of drug-metabolizing enzymes are known to affect the pharmacokinetics of drugs metabolized in the liver. Here, we assessed the effect of acetaminophen (APAP)-induced hepatotoxicity on the mRNA expression of drug-metabolizing enzymes and elucidated the underlying mechanism using three-dimensional (3D) cultures of HepG2 cells.2. 3D culture cells enabled us to establish an in vitro model of APAP-induced hepatotoxicity which showed the increase in N-acetyl-p-benzoquinone imine production, reactive oxygen species (ROS) generation and cellular injury.3. In this 3D culture model, APAP treatment significantly increased the mRNA expression of drug-metabolizing enzymes (cytochrome P450 [CYP]3A4, CYP2E1 and UDP-glucuronosyltransferase 1A6) and their nuclear receptors (pregnane X receptor and constitutive androstane receptor) compared with untreated cells. Treatment with N-acetylcysteine, a therapeutic agent for APAP-induced hepatotoxicity, suppressed these increases. In addition, the mRNA expression of drug-metabolizing enzymes and nuclear receptors were elevated depending on the concentration of H2O2, one of ROS involved in the development of APAP-induced hepatotoxicity. The mRNA expression of nuclear receptors increased before that of drug-metabolizing enzymes.4. In conclusion, ROS may induce the mRNA expression of nuclear receptors and promote the transcription of drug-metabolizing enzymes in the in vitro model of APAP-induced hepatotoxicity. |
| 巻・号 | 50(6) |
| ページ | 654-662 |
| 公開日 | 2020-6-1 |
| DOI | 10.1080/00498254.2019.1683258 |
| PMID | 31631733 |
| MeSH | Acetaminophen / metabolism* Acetaminophen / toxicity Chemical and Drug Induced Liver Injury / genetics Chemical and Drug Induced Liver Injury / metabolism* Constitutive Androstane Receptor Cytochrome P-450 CYP2E1 / metabolism Hep G2 Cells Hepatocytes / metabolism Humans Inactivation, Metabolic Liver Metabolic Clearance Rate RNA, Messenger / metabolism* Receptors, Cytoplasmic and Nuclear |
| IF | 1.902 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2(RCB1886) |