Chitosan Influences the Expression of P-gp and Metabolism of Norfloxacin in Grass Carp
The aim of this study was to investigate the relationship between the administration of chitosan (CTS), expression of permeability glycoprotein (P-gp), and the metabolism of norfloxacin (NOR) in Grass Carp Ctenopharyngodon idella. Fish were administrated with a single dose of either NOR, CTS, 1:5 NO...
| Veröffentlicht in: | Journal of aquatic animal health. - 1998. - 27(2015), 2 vom: 22. Juni, Seite 104-11 |
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| Weitere Verfasser: | , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2015
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| Zugriff auf das übergeordnete Werk: | Journal of aquatic animal health |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't ATP Binding Cassette Transporter, Subfamily B, Member 1 Anti-Bacterial Agents RNA, Messenger Chitosan 9012-76-4 Norfloxacin N0F8P22L1P |
| Zusammenfassung: | The aim of this study was to investigate the relationship between the administration of chitosan (CTS), expression of permeability glycoprotein (P-gp), and the metabolism of norfloxacin (NOR) in Grass Carp Ctenopharyngodon idella. Fish were administrated with a single dose of either NOR, CTS, 1:5 NOR-CTS or 1:10 NOR-CTS. The P-gp expression was analyzed by immunohistochemistry and real time-PCR. The concentration of NOR was determined using HPLC. The mRNA and protein expression of P-gp in the fish intestine was significantly enhanced following a single dosage of 40 mg/kg NOR, and peak expression occurred at 3 h after drug administration (P < 0.05). A single dosage of both 1:5 NOR-CTS and 1:10 NOR-CTS reduced the intestinal P-gp expression to levels significantly lower than that from NOR alone (P < 0.05), but significantly higher than that from the control (P < 0.05). Interestingly, CTS alone also led to a slight decrease in P-gp expression. In addition, pharmacokinetic assays revealed a marked increase in area under the curve (AUC) of NOR with 1:5 and 1:10 NOR-CTS, by approximately 1.5-fold and threefold, respectively. Finally, the relative bioavailability of NOR after a single oral dosage of 1:5 and 1:10 NOR-CTS was enhanced to 148.02% and 304.98%, respectively. In this study, we demonstrated that the transmembrane glycoprotein P-gp regulates NOR metabolism in the intestine of Grass Carp, suggesting that NOR may be a direct substrate of P-gp. More importantly, we showed that CTS can inhibit P-gp expression in a dose-dependent manner and improve the relative bioavailability of NOR in this species |
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| Beschreibung: | Date Completed 18.09.2015 Date Revised 30.09.2020 published: Print Citation Status MEDLINE |
| ISSN: | 1548-8667 |
| DOI: | 10.1080/08997659.2014.993484 |