The effect of the antidepressant venlafaxine on gene expression of biotransformation enzymes in zebrafish (Danio rerio) embryos.

The effect of venlafaxine, a pharmaceutical commonly found in aquatic environment, was analyzed on non-target organism, Danio rerio (Hamilton, 1822). D. rerio embryos were treated by two different concentrations of venlafaxine: either concentration relevant in aquatic environment (0.3 µg/L) or concentration that was two orders of magnitude higher (30 µg/L) for the evaluation of dose-dependent effect. Time-dependent effect was rated at 24, 96, and 144 h post-fertilization (hpf). For gene expression, genes representing one of the phases of xenobiotic biotransformation (0 to III) were selected. The results of this study showed that the effect of venlafaxine on the zebrafish embryos is the most evident at hatching (96 hpf). At this time, the results showed a downregulation of gene expression in each phase of biotransformation and in both tested concentrations. In contrast, an upregulation of most of the genes was observed 144 hpf for both tested venlafaxine concentrations. The study shows that venlafaxine can affect the gene expression of biotransformation enzymes in D. rerio embryos even in the environmentally relevant concentration and thus disrupt the process of biotransformation. Moreover, the pxr regulation of genes seems to be disrupted after venlafaxine exposure in dose- and time-dependent manner.

Effects of waterborne antidepressants on non-target animals living in the aquatic environment: A review.

After application, antidepressants, like other pharmaceuticals, are excreted from human body in their native form or as metabolites and enter the aquatic environment via different pathways. As concentrations of antidepressant residues in water continue to increase, their effects on non-target animals are being discussed. The aim of this study is to summarize current knowledge about the effects of wateborne antidepressants on non-target animals living in surface waters - invertebrates, fish and amphibians. Selective serotonin reuptake inhibitors such as fluoxetine, sertraline, and citalopram have been found to effect behavior, reproduction, and development in both invertebrates and vertebrates. Venlafaxine, belonging to the group of selective serotonin-noradrenalin reuptake inhibitors, not only affected behavior but also showed the potential to reduce survival in fish. Tricylic antidepressants are known to have various side-effects when consumed by humans. Moreover, in fish, exposure resulted in a significant increase in mortality, developmental retardation, morphological anomalies, and pathological changes in brain, heart, and cranial and caudal kidney. In addition, changes in antioxidant enzyme activity as well as increased lipid peroxidation were observed, even at the lowest tested concentrations. According to current knowledge, antidepressants occuring in surface water are able to affect the behavior, reproduction, development, and survival of aquatic invertebrates and vertebrates.