Chitosan Influences the Expression of P-gp and Metabolism of Norfloxacin in Grass Carp.
J Aquat Anim Health
; 27(2): 104-11, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25997556
ABSTRACT
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, 15 NOR-CTS or 110 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 15 NOR-CTS and 110 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 15 and 110 NOR-CTS, by approximately 1.5-fold and threefold, respectively. Finally, the relative bioavailability of NOR after a single oral dosage of 15 and 110 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carpas
/
Norfloxacino
/
Regulação da Expressão Gênica
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Quitosana
/
Antibacterianos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Aquat Anim Health
Ano de publicação:
2015
Tipo de documento:
Article