An In Vivo Whole-Transcriptomic Approach to Assess Developmental and Reproductive Impairments Caused by Flumequine in Daphnia magna

Abstract

Among veterinary antibiotics, flumequine (FLU) is still widely used in aquaculture due to its efficacy and cost-effectiveness. Although it was synthesized more than 50 years ago, a complete toxicological framework of possible side effects on non-target species is still far from being achieved. The aim of this research was to investigate the FLU molecular mechanisms in Daphnia magna, a planktonic crustacean recognized as a model species for ecotoxicological studies. Two different FLU concentrations (2.0 mg L−1 and 0.2 mg L−1) were assayed in general accordance with OECD Guideline 211, with some proper adaptations. Exposure to FLU (2.0 mg L−1) caused alteration of phenotypic traits, with a significant reduction in survival rate, body growth, and reproduction. The lower concentration (0.2 mg L−1) did not affect phenotypic traits but modulated gene expression, an effect which was even more evident under the higher exposure level. Indeed, in daphnids exposed to 2.0 mg L−1 FLU, several genes related with growth, development, structural components, and antioxidant response were significantly modulated. To the best of our knowledge, this is the first work showing the impact of FLU on the transcriptome of D. magna.

Effect of chlorpyrifos‐exposure on the expression levels of CYP genes in Daphnia magna and examination of a possibility that an up‐regulated clan 3 CYP, CYP360A8, reacts with pesticides

“…Therefore, it is likely that the stress response generally seen in other organisms is also observed in D. magna although the individual roles of several peroxidase genes in D. magna remain unknown. In the reproduction test with 2.0 mg/L of antibiotics, flumequine‐exposure, four peroxidase genes, different from the genes that increased in our study, showed increased expression 19 …”

“…In D. magna , although the CYPs involved in xenobiotic metabolism are not understood so well as those in mammals or insects, the genome has been determined, and 43 genes for CYP, 22 genes for GST, and 52 genes for ABC transporter have been annotated as candidates that might contribute to detoxification 9 . There are also many reports on changes in the expression or the activity of stress response genes, together with CYP genes upon chemical exposure 10–19 . For example, exposure of D. magna to 8.6 mg/L of the herbicide atrazine up‐regulated the expression of several CYP and GST genes, 14 and that to 50–100 mg/L of the pharmaceutical acetaminophen increasing the expression of CYP370A13 16 .…”

“…For example, exposure of D. magna to 8.6 mg/L of the herbicide atrazine up‐regulated the expression of several CYP and GST genes, 14 and that to 50–100 mg/L of the pharmaceutical acetaminophen increasing the expression of CYP370A13 16 . Also, comprehensive analysis of gene expression by RNA sequencing (RNA‐seq) in reproduction study revealed that exposed to the veterinary antibiotic flumequine (2.0 mg/L) showed altered expression of several genes related with growth, development, structural components, and antioxidant response, together with up‐regulation of several CYP4C3 orthologs and down‐regulation of CYP3A41 ortholog 19 …”

A Review on Fluoroquinolones’ Toxicity to Freshwater Organisms and a Risk Assessment

“…A recent study has demonstrated the occurrence of this mechanism of toxicity in zebrafish embryos exposed to FQs [ 242 ]; in the aforementioned study, developmental neurotoxicity induced by norfloxacin was demonstrated to be mediated by the activation of NMDA receptors. The involvement of these receptors in mediating FQ toxicity has been reported also in D. magna exposed to flumequine, where NMDA type I was among the top upregulated genes [ 19 ].…”

“…Indeed, they bear the potential to affect biodiversity through their impacts on sensitive species. Moreover, the ability of these compounds to interact with genetic material and induce delayed, reproductive, and transgenerational toxicity [ 19 , 20 , 21 ] adds to the complexity of assessing their environmental risk.…”