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

Félix

Enviro Toxic and Chemistry

et al. 2022

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

Section: Resultssupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Enantioselective Ecotoxicity of Venlafaxine in Aquatic Organisms: Daphnia and Zebrafish

Félix

Enviro Toxic and Chemistry

et al. 2022

“…The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/toxics11040333/s1, Table S1: Information on primers used. References [92][93][94][95]…”

Section: Supplementary Materialsmentioning

confidence: 99%

Pesticides and Parabens Contaminating Aquatic Environment: Acute and Sub-Chronic Toxicity towards Early-Life Stages of Freshwater Fish and Amphibians

Medkova

Hollerová

Riesova

et al. 2023

Toxics

Self Cite

Pesticides and personal care products are two very important groups of contaminants posing a threat to the aquatic environment and the organisms living in it.. Therefore, this study aimed to describe the effects of widely used pesticides and parabens on aquatic non-target biota such as fish (using model organisms Danio rerio and Cyprinus carpio) and amphibians (using model organism Xenopus laevis) using a wide range of endpoints. The first part of the experiment was focused on the embryonal toxicity of three widely used pesticides (metazachlor, prochloraz, and 4-chloro-2-methyl phenoxy acetic acid) and three parabens (methylparaben, propylparaben, and butylparaben) with D. rerio, C. carpio, and X. laevis embryos. An emphasis was placed on using mostly sub-lethal concentrations that are partially relevant to the environmental concentrations of the substances studied. In the second part of the study, an embryo-larval toxicity test with C. carpio was carried out with prochloraz using concentrations 0.1, 1, 10, 100, and 1000 µg/L. The results of both parts of the study show that even the low, environmentally relevant concentrations of the chemicals tested are often able to affect the expression of genes that play either a prominent role in detoxification and sex hormone production or indicate cell stress or, in case of prochloraz, to induce genotoxicity.

“…VLX exposure also caused GST inhibition in mouse neurons (Abdel-Wahab and Salama, 2011). Additionally, the downregulation of the gstp2 gene has been observed in zebrafish embryos exposed for 96 h to 0.3 and 30 µg/L of VLX (Hodkovicova et al, 2020). Since GST acts on detoxification pathways, its inhibition could lead to a greater susceptibility to oxidative stress.…”

mentioning

confidence: 99%

Multi-level toxicity assessment of the antidepressant venlafaxine in embryos/larvae and adults of zebrafish (Danio rerio)

Oliveira,

Fascineli,

Oliveira

et al. 2023

Genet. Mol. Biol.

The toxic effects of venlafaxine (VLX) on aquatic organisms have already been verified and therefore are a proven matter of concern. Herein, we evaluated zebrafish embryos/adults after acute exposure to VLX. Embryos/larvae were exposed to different concentrations of VLX (100-1000 mg/L; 1.33 as a dilution factor), to evaluate mortality/developmental changos and to analyze biomarkers (0.002-100 mg/L). For adults, mortality, genotoxicity, and biomarkers were assessed in five different concentrations of VLX (1-100 mg/L). The median lethal concentration (LC 50 -168h) was 274.1 mg/L for embryos/larvae, and >100 mg/L for adults (LC 50 -96h). VLX decreased the heart rate frequency and caused premature hatching and lack of equilibrium in embryos/larvae exposed to different concentrations ranging from 100 to 562.5 mg/L. The activity of acetylcholinesterase (AChE) was inhibited in larvae exposed to 1, 25 and 100 mg/L. Glutathione-S-transferase (GST) activity was reduced in both larvae and adults after exposure to different concentrations, mainly at 25 mg/L. For both larvae and adults, lactate dehydrogenase (LDH) activity increased after 100 mg/L of VLX exposure. No DNA damage was observed in peripheral erythrocytes. Exposure to VLX may cause adverse effects on zebrafish in their early and adult life stages, interfering with embryo-larval development, and can induce physiological disturbances in adults.