title: Inhibition of CYP450 1A and 3A by berberine in crucian carp Carassius auratus gibelio.
abstract: Berberine has long been considered as an antibiotic candidate in aquaculture. However, studies regarding its effects on drug-metabolizing enzymes in fish are still limited. In the present study, the effects of berberine on cytochrome P4501A (CYP1A) and CYP3A in crucian carp were investigated. Injection of different concentrations of berberine (0, 5, 25, 50, and 100mg/kg) inhibited the CYP1A mRNA expression, thereby inhibiting further the catalytic activity of CYP1A-related ethoxyresorufin-O-deethylase (EROD). Furthermore, both CYP1A expression and EROD activity were further inhibited with increasing berberine concentrations. In addition, the CYP3A expressions at both the mRNA and the protein levels were downregulated by higher berberine concentrations. The catalytic activity of CYP3A-related erythromycin N-demethylase (ERND) was also inhibited by berberine at a dose of no less than 25mg/kg. Moreover, at the berberine concentration exceeding 25mg/kg, the inhibition of CYP3A expression and ERND activity increased with increasing berberine concentrations. In vitro experiments were also performed. When berberine was pre-incubated with the crucian carp liver microsomes, it competitively inhibited the corresponding EROD activity with the IC(50) of 11.7 μM. However, the ERND activity was slightly inhibited by berberine with the IC(50) of 206.4 μM. These results suggest that, in crucian carp, berberine may be a potent inhibitor to CYP1A, whereas the CYP3A inhibition needs a higher concentration of berberine.
authors.affiliation: East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences; Key and Open Laboratory of Marine and Estuarine Fisheries Resources and Ecology, Ministry of Agriculture, shanghai 200090, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Zhou
authors.forename: Xin-Cang
authors.initials: XC
authors.lastname: Li
authors.forename: Wen-Hong
authors.initials: WH
authors.lastname: Fang
authors.forename: Xian-Le
authors.initials: XL
authors.lastname: Yang
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Hu
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhou
authors.forename: Jun-Fang
authors.initials: JF
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors*; D065692:Cytochrome P-450 CYP3A Inhibitors; D006054:Goldfish / Q000378:metabolism; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D001599:Berberine; D019363:Cytochrome P-450 CYP1A1