Environmental level of the antidepressant venlafaxine induces behavioral disorders through cortisol in zebrafish larvae (Danio rerio)

Tang, Yaqiu; Mi, Ping; Li, Meijuan; Zhang, Shaozhi; Li, Jie; Feng, Xisheng

doi:10.1016/j.ntt.2020.106942

Cited by 19 publications

(11 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, similar doses of citalopram, another SSRI, did not lead to any significant changes in the swimming behavior of the tested larvae as compared to the control group [ 114 ]. However, studies by Tang and colleagues [ 115 ] demonstrated that the environmental concentrations of venlafaxine had a dual effect on the activity of Danio rerio larvae—at higher tested concentrations it reduced the mobility of zebrafish, while the lowest tested concentrations induced hyperlocomotion. The results of these experiments carried out in zebrafish also allow us to suggest that the mechanism of toxic action of venlafaxine may be associated with upregulation of the cAMP–pCREB pathway, which may also increase cortisol levels [ 115 ].…”

Section: Zebrafish In Neurological Studiesmentioning

confidence: 99%

Zebrafish as an Animal Model for Testing Agents with Antidepressant Potential

Lachowicz

Niedziałek

Rostkowska³

et al. 2021

Life

View full text Add to dashboard Cite

Depression is a serious mental disease that, according to statistics, affects 320 million people worldwide. Additionally, a current situation related to the COVID-19 pandemic has led to a significant deterioration of mental health in people around the world. So far, rodents have been treated as basic animal models used in studies on this disease, but in recent years, Danio rerio has emerged as a new organism that might serve well in preclinical experiments. Zebrafish have a lot of advantages, such as a quick reproductive cycle, transparent body during the early developmental stages, high genetic and physiological homology to humans, and low costs of maintenance. Here, we discuss the potential of the zebrafish model to be used in behavioral studies focused on testing agents with antidepressant potential.

show abstract

Section: Zebrafish In Neurological Studiesmentioning

confidence: 99%

Zebrafish as an Animal Model for Testing Agents with Antidepressant Potential

Lachowicz

Niedziałek

Rostkowska³

et al. 2021

Life

View full text Add to dashboard Cite

show abstract

“…For instance, changes were found in the spontaneous behavior of zebrafish exposed to 27.7 mg/L (Gupta et al, 2014; Huang et al, 2019) and increased time of prey capture in hybrid striped bass exposed to 250 and 500 μg/L. Tang et al (2021) observed morphological changes, increased activity in the light–dark test, and endocrine disruption effects in larvae exposed to 1 μg/L of ( R,S )‐VEN. Regarding invertebrates such as D. magna , ( R,S )‐VEN showed low toxicity on immobilization with a 48 h median concentration (EC50) value of 141.28 mg/L (Minguez et al, 2014), which is much higher than the reported environmental concentrations (Gracia‐Lor et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Ecotoxicity of Venlafaxine in Aquatic Organisms: Daphnia and Zebrafish

Ribeiro

Félix

Ribeiro

et al. 2022

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

Venlafaxine is a chiral antidepressant detected in aquatic compartments. It was recently included in the 3rd Watch List from the European Union. The present study aimed to investigate venlafaxine toxicity effects, targeting possible enantioselective effects, using two aquatic organisms, daphnia (Daphnia magna) and zebrafish (Danio rerio). Specimens were exposed to both racemate, (R,S)‐venlafaxine (VEN), and to pure enantiomers. Acute assays with daphnia showed that up to 50 000 μg/L of the (R,S)‐VEN induced no toxicity. Organisms were also exposed to sublethal concentrations (25–400 μg/L) of (R,S)‐, (R)‐ and (S)‐VEN, for 21 days. No significant effects on mortality, age at first reproduction, and size of the first clutch were observed. However, a decrease in fecundity was observed for both enantiomers at the highest concentration. Regarding zebrafish, the effects of venlafaxine on mortality, embryo development, behavior, biochemistry, and melanin pigmentation were investigated after 96 h of exposure to the range of 0.3–3000 μg/L. (R)‐VEN significantly increased the percentage of malformations in comparison with (S)‐VEN. Behavior was also enantiomer dependent, with a decrease in the total distance moved and an increase in avoidance behavior observed in organisms exposed to (R)‐VEN. Despite the biochemical variations, no changes in redox homeostasis were observed. (R)‐VEN also led to an increase in zebrafish pigmentation. The different susceptibility to venlafaxine and enantioselective effects were observed in zebrafish. Our results suggest that at environmental levels (R,S)‐VEN and pure enantiomers are not expected to induce harmful effects in both organisms, but (R)‐VEN increased malformations in zebrafish larvae, even at reported environmental levels. These results highlight the importance of including enantioselective studies for an accurate risk assessment of chiral pollutants. Environ Toxicol Chem 2022;41:1851–1864. © 2022 SETAC

show abstract

“…Fish were waterborne exposed to S -(−)- and R -(+)-metoprolol at a nominal concentration of 15 μg/L, while S -(+)- and R -(−)-venlafaxine were introduced at 3 μg/L. The quantities were based on the environmentally relevant levels in effluent-receiving Hong Kong waters (with reference to racemic metoprolol of 1.840 μg/L and racemic venlafaxine of 0.329 μg/L) and considering that seawater has lower concentrations of pollutants than other water bodies have, such as the high concentration of metoprolol (45 μg/L) and venlafaxine (2.19 μg/L) in black water (Friesland, the Netherlands) and wastewater effluent (MN). ,, The actual waterborne concentrations of S - and R -metoprolol and S - and R -venlafaxine detected during the uptake period were 10.8, 14.4, 2.3, and 2.6 μg/L, respectively. Fish were sampled at 10 time points (days 0, 1, 2, 3, 6, 10, 15, 20, 24, and 28) during the exposure period and at six time points (days 29, 30, 31, 34, 38, and 42) during the clearance period.…”

Section: Methodsmentioning

confidence: 99%

Enantiospecific Uptake and Depuration Kinetics of Chiral Metoprolol and Venlafaxine in Marine Medaka (Oryzias melastigma): Tissue Distribution and Metabolite Formation

Jin

Wang

Meng

et al. 2023

Environ. Sci. Technol.

View full text Add to dashboard Cite

The increasing use of chiral pharmaceuticals has led to their widespread presence in the environment. However, their toxicokinetics have rarely been reported. Therefore, the tissue-specific uptake and depuration kinetics of two pairs of pharmaceutical enantiomers, S-(−)-metoprolol versus R-(+)-metoprolol and S-(+)-venlafaxine versus R-(−)-venlafaxine, were studied in marine medaka (Oryzias melastigma) during a 28-day exposure and 14-day clearance period. The toxicokinetics of the studied pharmaceuticals, including uptake and depuration rate constants, depuration half-life (t 1/2 ), and bioconcentration factor (BCF), were reported for the first time. The whole-fish results demonstrated a higher S-than Rvenlafaxine bioaccumulation potential, whereas no significant difference was observed between S-and R-metoprolol. O-desmethyl-metoprolol (ODM) and α-hydroxy-metoprolol (AHM) were the main metoprolol metabolites identified by suspect screening, and the ratios of ODM to AHM were 3.08 and 1.35 for S-and R-metoprolol, respectively. N,O-Didesmethyl-venlafaxine (NODDV) and Ndesmethyl-venlafaxine (NDV) were the main venlafaxine metabolites, and the ratios of NODDV to NDV were 1.55 and 0.73 for Sand R-venlafaxine, respectively. The highest tissue-specific BCFs of the four enantiomers were all found in the eyes, meriting indepth investigation.

show abstract

Environmental level of the antidepressant venlafaxine induces behavioral disorders through cortisol in zebrafish larvae (Danio rerio)

Cited by 19 publications

References 43 publications

Zebrafish as an Animal Model for Testing Agents with Antidepressant Potential

Zebrafish as an Animal Model for Testing Agents with Antidepressant Potential

Enantioselective Ecotoxicity of Venlafaxine in Aquatic Organisms: Daphnia and Zebrafish

Enantiospecific Uptake and Depuration Kinetics of Chiral Metoprolol and Venlafaxine in Marine Medaka (Oryzias melastigma): Tissue Distribution and Metabolite Formation

Contact Info

Product

Resources

About