Effects of fish CYP inducers on difloxacin N-demethylation in kidney cell of Chinese idle (Ctenopharyngodon idellus)
A drug–drug interaction occurs when the effect of one drug is altered by the presence of another drug which is generally associated with the induction of cytochrome P450s (CYPs) activity. Thus, unexpected treatment failures often happen resulting from inappropriate coadministration in fisheries. However, little information is available about CYP induction in fish. The reaction of difloxacin (DIF) biotransformation to sarafloxacin (SAR) belongs to N-demethylation catalyzed mainly by CYP(s). In order to supply useful information on CYP induction, the present study assessed the effects of fish-specific CYP inducers on DIF N-demethylation and enzyme kinetics in kidney cell of Chinese idle (CIK; grass carp (Ctenopharyngodon idellus)) by RP-HPLC. Results demonstrated that the amounts of SAR formation and enzymatic parameters Clint and Vmax were significantly increased due to β-naphthoflavone (BNF) pretreatment. Therefore, we suggest that CYP1A may be involved in DIF N-demethylation in CIK. This study provides instructive information to ensure treatment success via avoiding CYP induction in fisheries.
KeywordsChinese idle CYP Difloxacin Grass carp Kinetics RP-HPLC Sarafloxacin
Kidney cell of Chinese idle
Grass carp liver cell line
Reversed-phase high-performance liquid chromatography
This work was financially supported by the National Natural Science Foundation of China (No. 30371109).
- Li D, Yang XL, Zhang SJ et al (2008) Effects of mammalian CYP3A inducers on CYP3A-related enzyme activities in grass carp (Ctenopharyngodon idellus): Possible implications for the establishment of a fish CYP3A induction model. Comp Biochem Physiol C 147:17–29Google Scholar
- Lin M, Yang XL, Fang WH et al (2006) Dose–response of inducers to effect on EROD in grass carp hepatocyte. J Fish China 30:311–315Google Scholar
- Lin M, Yang XL, Wang XL et al (2007) Enzymatic on deethlation metabolism of enrofloxacin in grass carp hepatocyte. High Technol Lett (Chinese version) 17:314–318Google Scholar
- Wan XQ, Wu WZ, He JZ (2002) Evaluating toxic effects of PCDD/F using grass carp primary hepatocyte culture. China Environ Sci 22:114–117Google Scholar
- Wang XL, Yang XL, Lin M, Yu WJ et al (2007) Elimination of enrofloxacin and detection of metabol ic enzyme activity in Micropterus salmoides hepatocytes. J Fish Sci China 14:1004–1005Google Scholar