Transport of pharmaceuticals and their metabolites between water and sediments as a further potential exposure for aquatic organisms

Koba, Olga; Grabicová, Kateřina; Červený, Daniel; Turek, Jan; Kolářová, Jitka; Randák, Tomáš; Žlábek, Vladimír; Grabic, Roman

doi:10.1016/j.jhazmat.2017.08.039

Cited by 73 publications

(28 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… Schultz et al (2011) warned of the chronic exposure effects of this compound because of its bioaccumulative properties. A plethora of studies have found a significant bioaccumulation of sertraline in tissues ( Chen, Gong & Kelly, 2017 ; Grabicova et al, 2017 ; Koba et al, 2018 ; Xie et al, 2015 ; Grabicova et al, 2014 ). Specifically, sertraline was found in the liver and other tissues, including the brain, kidneys, gills and muscles ( Xie et al, 2015 ; Grabicova et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Environmentally relevant levels of four psychoactive compounds vary in their effects on freshwater fish condition: a brain concentration evidence approach

Hubená

Horký

Grabic

et al. 2020

PeerJ

Self Cite

View full text Add to dashboard Cite

Background The aquatic environment has been contaminated with various anthropogenic pollutants, including psychoactive compounds that may alter the physiology and behavior of free-living organisms. The present study focused on the condition and related mortality of the juvenile chub (Squalius cephalus). The aim of the study was to test whether the adverse effects of the antidepressants sertraline and citalopram, the analgesic tramadol and the illicit drug methamphetamine, on fish condition exist under environmentally relevant concentrations and whether these effects persist after a depuration period. Innovative analyses of the fish brain concentrations of these compounds were performed with the aim to show relationship between compound brain tissue concentration and fish condition. Methods The laboratory experiment consisted of 42 days of exposure and a subsequent 14-day depuration period with regular monitoring of the condition and mortality of exposed and control fish. Identical methodology, including individual brain concentration analyses for the tested compounds, was applied for all substances. Additional study on feeding under sertraline exposure was also conducted. The feeding was measured from the 28th day of the exposure, three times in a week, by observation of food intake during 15 minutes in social environment. Results The effects of particular psychoactive compounds on chub condition varied. While sertraline induced a lower condition and increased mortality, the effects of methamphetamine were inverse, and tramadol and citalopram had no significant effect at all. Individual brain concentrations of the tested compounds showed that the effects of sertraline and methamphetamine on fish condition were increased with brain concentration increases. Additionally, the food intake was reduced in case of sertraline. In contrast, there was no relationship between tramadol and citalopram brain tissue concentration and fish condition, suggesting that the concentration-dependent effect is strongly compound-specific. Methamphetamine was the only compound with a persistent effect after the depuration period. Our results demonstrate the suitability of the brain concentration evidence approach and suggest that changes in fish condition and other related parameters can be expected in freshwater ecosystems polluted with specific psychoactive compounds.

show abstract

Section: Discussionmentioning

confidence: 99%

Environmentally relevant levels of four psychoactive compounds vary in their effects on freshwater fish condition: a brain concentration evidence approach

Hubená

Horký

Grabic

et al. 2020

PeerJ

Self Cite

View full text Add to dashboard Cite

show abstract

“…Selected pharmaceuticals are widely prescribed in European countries [29,30] and have been routinely reported in different sample matrices, like sediment, sludge, soil, plants, and fish. Eighteen pharmaceuticals and seven metabolites have been identified in water and sediments from the pond, which receives discharged water from the WWTP of Vodňany town [20]. Fish living in that pond show the presence of 14 pharmaceuticals, including four parent compounds and their main metabolites (N-desmethylcitalopram, norsertraline, metoprolol acid, and O-desmethylvenlafaxine) in hepatic tissues [19,20].…”

Section: Discussionmentioning

confidence: 99%

“…Eighteen pharmaceuticals and seven metabolites have been identified in water and sediments from the pond, which receives discharged water from the WWTP of Vodňany town [20]. Fish living in that pond show the presence of 14 pharmaceuticals, including four parent compounds and their main metabolites (N-desmethylcitalopram, norsertraline, metoprolol acid, and O-desmethylvenlafaxine) in hepatic tissues [19,20]. However, it is not known whether these metabolites were taken up from the surrounding aquatic environment or produced by fish from the original compounds.…”

Section: Discussionmentioning

confidence: 99%

“…Citalopram is a selective serotonin reuptake inhibitor medication and is one of the most prescribed and used antidepressants in the world [41], due to its low potential to show clinically relevant drug-drug interactions, lower binding affinity to serum proteins, and low cardiac toxicity compared to other antidepressants [42][43][44]. Citalopram and its metabolite N-desmethylcitalopram were found in different environmental matrices (water, sediment, and fish) of the pond which received discharged water from WWTP of Vodňany town [20]. The average concentration of citalopram and N-desmethylcitalopram found in all analyzed hepatic tissue of common carp was 3.1 ± 2.9, and 2.6 ± 1.4 ng/g wet weight, respectively [19].…”

Section: Discussionmentioning

confidence: 99%

“…However, under well-controlled experimental conditions, when fish are kept in water tanks, and pure pharmaceuticals (e.g., diltiazem) are applied to water for research purposes, the presence of metabolites after a certain time was also detected in water [17,18]. Therefore, in in situ tests in cascade ponds in Vodňany town, citalopram, metoprolol, sertraline, venlafaxine, and their metabolites have been detected in common carp fish hepatic tissue, water, and soil [19,20]. It is uncertain whether the metabolites, which have been previously detected in the pond, are at least partly produced during hepatic metabolism in fish and excreted back to the water.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

In Vitro Metabolic Transformation of Pharmaceuticals by Hepatic S9 Fractions from Common Carp (Cyprinus carpio)

et al. 2020

Self Cite

View full text Add to dashboard Cite

Water from wastewater treatment plants contains concentrations of pharmaceutically active compounds as high as micrograms per liter, which can adversely affect fish health and behavior, and contaminate the food chain. Here, we tested the ability of the common carp hepatic S9 fraction to produce the main metabolites from citalopram, metoprolol, sertraline, and venlafaxine. Metabolism in fish S9 fractions was compared to that in sheep. The metabolism of citalopram was further studied in fish. Our results suggest a large difference in the rate of metabolites formation between fish and sheep. Fish hepatic S9 fractions do not show an ability to form metabolites from venlafaxine, which was also the case for sheep. Citalopram, metoprolol, and sertraline were metabolized by both fish and sheep S9. Citalopram showed concentration-dependent N-desmethylcitalopram formation with Vmax = 1781 pmol/min/mg and Km = 29.7 μM. The presence of ellipticine, a specific CYP1A inhibitor, in the incubations reduced the formation of N-desmethylcitalopram by 30–100% depending on the applied concentration. These findings suggest that CYP1A is the major enzyme contributing to the formation of N-desmethylcitalopram. In summary, the results from the present in vitro study suggest that common carp can form the major metabolites of citalopram, metoprolol, and sertraline.

show abstract

Venlafaxine exposure alters mitochondrial respiration and mitomiR abundance in zebrafish brains

Robichaud,

Bragg,

Servos

et al. 2024

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

Wastewater treatment plant (WWTP) effluent often releases pharmaceuticals like venlafaxine (a serotonin–norephinephrine reuptake inhibitor antidepressant) to freshwater ecosystems at levels causing adverse metabolic effects on fish. Changes to fish metabolism can be regulated by epigenetic mechanisms like microRNA (small RNA molecules that regulate mRNA translation), including regulating mitochondrial mRNAs. Nuclear‐encoded microRNAs regulate mitochondrial gene expression in mammals, and have predicted effects in fish. We aimed to identify whether venlafaxine exposure changed mitochondrial respiration and resulted in differentially abundant mitochondrial microRNA (mitomiRs) in zebrafish brains. In vitro exposure of brain homogenate to below environmentally relevant concentrations of venlafaxine (<1 µg/L) caused a decrease in mitochondrial respiration, although this was not driven by changes to mitochondrial Complex I or II function. To identify whether these effects occur in vivo, zebrafish were exposed to 1 µg/L venlafaxine for 0, 1, 6, 12, 24, and 96 h. In vivo, venlafaxine exposure had no significant effects on brain mitochondrial respiration; however, select mitomiRs (dre‐miR‐301a‐5p, dre‐miR‐301b‐3p, and dre‐miR‐301c‐3p) were also measured, because they were bioinformatically predicted to regulate mitochondrial cytochrome c oxidase subunit I (COI) abundance. These mitomiRs were differentially regulated based on venlafaxine exposure (with miR‐301c‐3p abundance differing during the day and miR‐301b‐3p being lower in exposed fish at night), and with respect to sex and time sampled. Overall, the results demonstrated that in vitro venlafaxine exposure to zebrafish brain caused a decrease in mitochondrial respiration, but these effects were not seen after acute in vivo exposure. Results may have differed because in vivo exposure allows for fish to mitigate effects through mechanisms that could include mitomiR regulation, and because fish were only acutely exposed. Environ Toxicol Chem 2024;00:1–14. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

show abstract

Transport of pharmaceuticals and their metabolites between water and sediments as a further potential exposure for aquatic organisms

Cited by 73 publications

References 39 publications

Environmentally relevant levels of four psychoactive compounds vary in their effects on freshwater fish condition: a brain concentration evidence approach

Environmentally relevant levels of four psychoactive compounds vary in their effects on freshwater fish condition: a brain concentration evidence approach

In Vitro Metabolic Transformation of Pharmaceuticals by Hepatic S9 Fractions from Common Carp (Cyprinus carpio)

Venlafaxine exposure alters mitochondrial respiration and mitomiR abundance in zebrafish brains

Contact Info

Product

Resources

About