Effects of norfloxacin on hepatic genes expression of P450 isoforms (CYP1A and CYP3A), GST and P-glycoprotein (P-gp) in Swordtail fish (Xiphophorus Helleri)

Abstract

The presence of antibiotics including norfloxacin in the aquatic environment may cause adverse effects in non-target organisms. But the toxic mechanisms of fluoroquinolone to fish species are still not completely elucidated. Thus, it is essential to investigate the response of fish to the exposure of fluoroquinolone at molecular or cellular level for better and earlier prediction of these environmental pollutants toxicity. The sub-chronic toxic effects of norfloxacin (NOR) on swordtail fish (Xiphophoru s helleri) were investigated by measuring mRNA expression of cytochrome P450 1A (CYP1A), cytochrome P450 3A (CYP3A), glutathione S-transferase (GST) and P-glycoprotein (P-gp) and their corresponding enzyme activities (including ethoxyresorufin O-deethylase, erythromycin N-demethylase and GST. Results showed that NOR significantly affected the expression of CYP1A, CYP3A, GST and P-gp genes in swordtails. The gene expressions were more responsive to NOR exposure than their corresponding enzyme activities. Moreover, sexual differences were found in gene expression and enzyme activities of swordtails exposed to NOR. Females displayed more dramatic changes than males. The study further demonstrated that the combined biochemical and molecular parameters were considered as useful biomarkers to improve our understanding of potential ecotoxicological risks of NOR exposure to aquatic organisms.

A global analysis on the systemic effects of antibiotics in cultured fish and their potential human health risk: a review

“…2018), bath at environmental relevant levels (Liang et al . 2015) and injection (Vaccaro et al . 2003; Hu et al .…”

“…2012) and gender (Liang et al . 2015) specific differences. Such suppression indicates limited ability to counteract excessive oxidative stress caused by antibiotics, which may sustain their toxicity and thus damage fish tissues (Smith et al .…”

Treatment of the Fluoroquinolone‐Associated Disability: The Pathobiochemical Implications

“…Liang et al [90] measured the subchronic toxic effects of NOR on a swordtail fish by measuring mRNA expression of cytochrome P450 1A (CYP1A), cytochrome P-450 3A (CYP3A), glutathione S-transferase (GST), P-glycoprotein (P-gp), and their corresponding enzyme activities. Results showed that NOR significantly affected the expression of CYP1A, CYP3A, GST, and P-gp genes in swordtails.…”

Effects of CYP1A enzyme specific inhibitor on pharmacokinetics of para-acetaminophen in Bactrian camel

“…CYP1A enzyme activities are inhibited by many factors, including the environment, diet, and co-administration of drugs. For example, CYP1A enzyme activities are strongly inhibited by quinolones ( e.g ., lomefloxacin, ciprofloxacin, and gatifloxacin), fluvoxamine, furafylline, oral contraceptives, and some traditional Chinese medicines [1011121314]. Al-Mohizea et al [10] studied the effects of Acacia catechu on the pharmacokinetics of theophylline, a CYP1A-enzyme-specific substrate, in rabbits.…”

“…They reported that all of the fluoroquinolones studied inhibited CYP1A in a non-competitive manner and that several altered CYP1A activity via mechanism-based inhibition that is irreversible and cumulative. Thus, prolonged treatment with these substances may inhibit CYP1A activity in a manner that can result in serious drug-drug interactions [12]. Wijnands et al [14] reported that total body clearance of theophylline in humans was significantly decreased by enoxacin, ciprofloxacin, and pefloxacin.…”