Effects of enrofloxacin on cytochromes P4501A and P4503A in Carassius auratus gibelio (crucian carp)

Abstract

Currently, although enrofloxacin (EF) as a widely used veterinary medicine has begun to apply to treating fish bacterial infections, the researches on the effects of EF on their main drug metabolic enzymes are limited. To investigate the effects of EF on fish cytochromes P450 (CYPs) 1A and 3A, the enzymatic activities and expressions (mRNA and protein) of crucian carp CYP1A and CYP3A after EF administration were examined. For CYP1A, in the in vivo experiments, EF exhibited potent inhibition on the CYP1A-related ethoxyresorufin-O-deethylase (EROD) activity, as well as CYP1A expressions at both protein and mRNA levels, at 24 h after administration with different EF dosages (3, 10, 30, and 60 mg/kg); Furthermore, CYP1A enzymatic activity and expressions at both protein and mRNA levels decreased more with increasing EF dosages. Additionally, the in vitro experimental results showed that, after incubated with microsomes, EF did not change the EROD activity through interacting directly with CYP1A. For CYP3A, the in vitro and in vivo experimental results demonstrated that EF could inhibit the CYP3A-related erythromycin N-demethylase activity in a time- and dose-dependent manner, while it did not suppress CYP3A expressions at both protein and mRNA levels after administration with EF for a short period (no more than 24 h); however, after injection with EF at a high dose (10 mg/kg) for a long period, the CYP3A protein and mRNA reached their lowest levels at 96 and 48 h, respectively. These results indicate that EF can suppress CYP1A expressions in a dose-dependent manner, thereby inhibiting further its catalytic activity; meanwhile, both the interactions of EF with CYP3A and the expressions decrease (protein and mRNA) caused by EF contribute to the CYP3A inhibition.

Piscine cytochromes P450 (CYP) and their response to antimicrobial drugs

“…injection of 3 mg kg À1 of EF or multi-doses of 1 mg kg À1 were sufficient to cause a generalized depression of CYP activities in sea bass. Enrofloxacin was an effective inactivator of the erythromycin N-demethylase activity (Vaccaro et al 2003;Hu et al 2012), while immunoblot analysis showed a strong decrease in staining intensity of a protein band immunoreactive with anti-CYP3A27. Therefore, it can be postulated that fluoroquinoloneantibiotics such as EF in sea bass have an adverse reaction with the CYP enzymes, and hence a strong potential to cause long-lasting interactions.…”

“…; Hu et al . ), while immunoblot analysis showed a strong decrease in staining intensity of a protein band immunoreactive with anti‐CYP3A27. Therefore, it can be postulated that fluoroquinolone‐antibiotics such as EF in sea bass have an adverse reaction with the CYP enzymes, and hence a strong potential to cause long‐lasting interactions.…”

“…Pretranslational suppression of CYP1A induction was found in spawning females. Enrofloxacin exhibited potent inhibition on the CYP1A-related EROD activity as well as CYP1A expressions at both protein an mRNA levels in crucian carp (Hu et al 2012). In sea bass, EF was proven able to provoke the inactivation of the CYP3A enzyme (Vaccaro et al 2003).…”

“…At this time, however, most research on the CYP system in fish has been done on environmental factors that influence CYP induction. Much less is known about metabolism of aquaculture antibiotics by the CYP system (Snegaroff, Bach & Prevost 1989;Ishida 1992;Moutou, Burke & Houlihan 1998;Vaccaro, Giorgi, Longo, Mengozzi & Gervasi 2003;Topic Popovic, Babish & Bowser 2007;Yu & Yang 2009;Zhou, Li, Fang, Yang, Hu, Zhou & Zhou 2011;Hu, Li, Sun, Fang, Zhou, Hu & Zhou 2012;Topic Popovic, Howell, Babish & Bowser 2012).…”

Effect of Trichlorfon on Hepatic Lipid Accumulation in Crucian Carp Carassius auratus gibelio

“…Crucian carp is an omnivorous freshwater fish native to China. Aquaculture of this fish in China has expanded rapidly because of its fast growth, use of natural foods, tender flesh, and high resistance to disease (Hu et al 2012). However, very few reports are available concerning hepatic lipid metabolism in this fish subjected to trichlorfon exposure.…”