In Vivo and In Vitro Induction of Cytochrome P450 3A4 by Thalidomide in Humanized-Liver Mice and Experimental Human Hepatocyte HepaSH cells
Autoinduction of cytochrome P450 (P450) 3A4-mediated metabolism of thalidomide was investigated in humanized-liver mice and human hepatocyte-derived HepaSH cells. The mean plasma ratios of 5-hydroxythalidomide and glutathione adducts to thalidomide were significantly induced (3.5- and 6.0-fold, respectively) by thalidomide treatment daily at 1000 mg/kg for 3 days and measured at 2 h after the fourth administration (on day 4). 5-Hydroxythalidomide was metabolically activated by P450 3A4 in HepaSH cells pretreated with 300 and 1000 μM thalidomide, and 5,6-dihydroxythalidomide was detected. Significant induction of P450 3A4 mRNA expression (4.1-fold) in the livers of thalidomide-treated mice occurred. Thalidomide exerts a variety of actions through multiple mechanisms following bioactivation by induced human P450 3A enzymes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Chemical research in toxicology - (2024) vom: 16. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Uehara, Shotaro [VerfasserIn] |
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Date Revised 16.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1021/acs.chemrestox.4c00069 |
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NLM37115507X |
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| 245 | 1 | 0 | |a In Vivo and In Vitro Induction of Cytochrome P450 3A4 by Thalidomide in Humanized-Liver Mice and Experimental Human Hepatocyte HepaSH cells |
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| 520 | |a Autoinduction of cytochrome P450 (P450) 3A4-mediated metabolism of thalidomide was investigated in humanized-liver mice and human hepatocyte-derived HepaSH cells. The mean plasma ratios of 5-hydroxythalidomide and glutathione adducts to thalidomide were significantly induced (3.5- and 6.0-fold, respectively) by thalidomide treatment daily at 1000 mg/kg for 3 days and measured at 2 h after the fourth administration (on day 4). 5-Hydroxythalidomide was metabolically activated by P450 3A4 in HepaSH cells pretreated with 300 and 1000 μM thalidomide, and 5,6-dihydroxythalidomide was detected. Significant induction of P450 3A4 mRNA expression (4.1-fold) in the livers of thalidomide-treated mice occurred. Thalidomide exerts a variety of actions through multiple mechanisms following bioactivation by induced human P450 3A enzymes | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Murayama, Norie |e verfasserin |4 aut | |
| 700 | 1 | |a Higuchi, Yuichiro |e verfasserin |4 aut | |
| 700 | 1 | |a Shimizu, Makiko |e verfasserin |4 aut | |
| 700 | 1 | |a Suemizu, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Guengerich, F Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Yamazaki, Hiroshi |e verfasserin |4 aut | |
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