Exposure to tricyclic antidepressant nortriptyline affects early-life stages of zebrafish (Danio rerio)

Ana C Oliveira,Maria L Fascineli,Thayres S Andrade,Diego Sousa-Moura,Inês Domingues,Níchollas S Camargo,Rhaul Oliveira,Cesar K Grisolia,Rolando A.R Villacis

doi:10.1016/j.ecoenv.2020.111868

Abstract

Psychiatric drugs are among the leading medications prescribed for humans, with their presence in aquatic environments raising concerns relating to potentially harmful effects on non-target organisms. Nortriptyline (NTP) is a selective serotonin-norepinephrine reuptake inhibitor antidepressant, widely used in clinics and found in environmental water matrices. In this study, we evaluated the toxic effects of NTP on zebrafish (Danio rerio) embryos and early larval stages. Developmental and mortality analyses were performed on zebrafish exposed to NTP for 168 h at concentrations ranging from 500 to 46,900 µg/L. Locomotor behaviour and acetylcholinesterase (AChE) activity were evaluated by exposing embryos/larvae to lower NTP concentrations (0.006–500 µg/L). The median lethal NTP concentration after 168 h exposure was 2190 µg/L. Although we did not identify significant developmental changes in the treated groups, lack of equilibrium was already visible in surviving larvae exposed to ≥ 500 µg/L NTP. The behavioural analyses showed that NTP was capable of modifying zebrafish larvae swimming behaviour, even at extremely low (0.006 and 0.088 µg/L) environmentally relevant concentrations. We consistently observed a significant reduction in AChE activity in the animals exposed to 500 µg/L NTP. Our results highlight acute toxic effects of NTP on the early-life stages of zebrafish. Most importantly, exposure to environmentally relevant NTP concentrations may affect zebrafish larvae locomotor behaviour, which in turn could reduce the fitness of the species. More studies involving chronic exposure and sensitive endpoints are warranted to better understand the effect of NTP in a more realistic exposure scenario.

Highlights

Pharmaceuticals are widely prescribed around the world and their presence in aquatic environments has gained increased attention in recent years due to concerns about negative effects on non-target or ganisms (Ross et al, 2012; aus Der Beek et al, 2016)
The present study aimed to evaluate the toxicity of NTP on zebrafish embryos and larvae using an integrated approach with multiple endpoints, which included environmen tally relevant NTP concentrations and sensitive parameters with ecological relevance
The LC50 calculations indicated that embryos/ larvae became more sensitive to NTP as the exposure time increased; we observed the lowest LC50 (2190 μg/L) after 168 h (Table 1)

Summary

Introduction

Pharmaceuticals are widely prescribed around the world and their presence in aquatic environments has gained increased attention in recent years due to concerns about negative effects on non-target or ganisms (Ross et al, 2012; aus Der Beek et al, 2016). Antidepressants are known for their specific mode of action and many studies have shown that this type of pharmaceutical may induce side-effects in aquatic organisms, including reduction in aggressiveness, disturbance of fertility and development, and inhibition of feeding ac tivity (Henry and Black, 2008; Sanchez-Argüello et al, 2009; Arnnok et al, 2017)

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Conclusion