Varying the exposure period and duration of neuroactive pharmaceuticals and their metabolites modulates effects on the visual motor response in zebrafish (Danio rerio) larvae

Huang, Irvin J.; Sirotkin, Howard I.; McElroy, Anne E.

doi:10.1016/j.ntt.2019.01.006

Cited by 61 publications

(32 citation statements)

References 52 publications

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“…The persistence of pharmaceuticals in the aquatic environment allows for scenarios of chronic exposure, highlighting the importance of exposure time in determining the severity of pharmaceutical impact on nontarget organisms. The relative importance of contaminant concentration versus exposure duration has so far been little studied, with only a few studies focusing on the exposure length as a main parameter (Cope et al 2008;Huang et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Long-term exposure of marine mussels to paracetamol: is time a healer or a killer?

Koagouw

Stewart

Ciocan

2021

Environ Sci Pollut Res

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Pharmaceuticals pose a major threat to the marine environment, and several studies have recently described their negative effects on marine organisms. Pharmaceutical compounds are constantly being released into aquatic ecosystems, and chronic exposure, even at low concentrations, may have a major impact on marine organisms. The purpose of the present study is to evaluate the biological changes induced by one of the most widely used pharmaceuticals-paracetamol-in the blue mussel Mytilus edulis, after a long-term exposure at environmentally relevant concentrations. We present our data alongside and in comparison with results from a previous short-term exposure, to demonstrate the significance of exposure period on the effects of paracetamol in adult blue mussels. After 24 days of laboratory exposure, seven potential target genes were selected to examine toxicological effects in mussels' gonads and possible disruptive effects on reproductive processes. The results show the modulation of some important reproduction-related genes: estrogen receptor-2 (ER2), vitelline envelope zona pellucida domain-9 (V9), and vitellogenin (VTG). Variations in mRNA expression of four other genes involved in apoptosis (HSP70, CASP8, BCL2, and FAS) are also highlighted. Histopathological alterations caused by paracetamol, together with neutral red retention time response in mussels' hemocytes, are presented herein. Overall, this study highlights the exacerbated effects of low concentration of paracetamol after chronic exposure, similar to the damage induced by higher concentrations in a short exposure scenario, thus emphasizing the importance of length of exposure period when studying the effects of this substance. Additionally, this study also discusses the potential of paracetamol to inflict several major changes in the reproductive system of mussels and thus possibly affect the survival of populations.

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Section: Introductionmentioning

confidence: 99%

Long-term exposure of marine mussels to paracetamol: is time a healer or a killer?

Koagouw

Stewart

Ciocan

2021

Environ Sci Pollut Res

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“…The primary target molecule of fluoxetine (the serotonin transport molecule) is conserved across all vertebrate taxa [7], and, thus, fluoxetine has the potential to affect a diverse array of ecologically important behaviours in wildlife [8,9]. Indeed, there is growing evidence that antidepressants, such as fluoxetine, can disrupt a range of behaviours in non-target species at environmentally relevant concentrations, such as activity [10][11][12][13], anxiety [14][15][16], predator avoidance and escape [17][18][19][20], and foraging [21,22]. However, to date, few studies have considered how impacts of psychoactive pollutants might be affected by social context [23,24], and fewer still have directly asked whether impacts seen in social isolation are reflective of those in a social context [25].…”

Section: Introductionmentioning

confidence: 99%

Field-realistic antidepressant exposure disrupts group foraging dynamics in mosquitofish

et al. 2019

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Psychoactive pollutants, such as antidepressants, are increasingly detected in the environment. Mounting evidence suggests that such pollutants can disrupt the behaviour of non-target species. Despite this, few studies have considered how the response of exposed organisms might be mediated by social context. To redress this, we investigated the impacts of two environmentally realistic concentrations of a pervasive antidepressant pollutant, fluoxetine, on foraging behaviour in fish ( Gambusia holbrooki ), tested individually or in a group. Fluoxetine did not alter behaviour of solitary fish. However, in a group setting, fluoxetine exposure disrupted the frequency of aggressive interactions and food consumption, with observed effects being contingent on both the mean weight of group members and the level of within-group variation in weight. Our results suggest that behavioural tests in social isolation may not accurately predict the environmental risk of chemical pollutants for group-living species and highlight the potential for social context to mediate the effects of psychoactive pollutants in exposed wildlife.

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“…Therefore, venlafaxine and its metabolite, which were found in fish tissue from the pond system, were removed from the water. Venlafaxine and O-desmethylvenlafaxine could be bioavailable in the fish circulation system and provoke adverse effects, which is connected with changes in behavioral performance [40].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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Varying the exposure period and duration of neuroactive pharmaceuticals and their metabolites modulates effects on the visual motor response in zebrafish (Danio rerio) larvae

Cited by 61 publications

References 52 publications

Long-term exposure of marine mussels to paracetamol: is time a healer or a killer?

Long-term exposure of marine mussels to paracetamol: is time a healer or a killer?

Field-realistic antidepressant exposure disrupts group foraging dynamics in mosquitofish

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

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