Characterizing toxicity pathways of fluoxetine to predict
adverse outcomes in adult fathead minnows (Pimephales promelas)

J 2022

Characterizing toxicity pathways of fluoxetine to predict adverse outcomes in adult fathead minnows (Pimephales promelas)

COLVILLE, Carly, Alper James ALCARAZ, Derek GREEN, Bradley PARK, Jianguo XIA et. al.

Basic information

Original name

Characterizing toxicity pathways of fluoxetine to predict adverse outcomes in adult fathead minnows (Pimephales promelas)

Authors

COLVILLE, Carly (124 Canada), Alper James ALCARAZ (124 Canada), Derek GREEN (124 Canada), Bradley PARK (124 Canada), Jianguo XIA (124 Canada), Othman SOUFAN (124 Canada), Pavel HRUŠKA (203 Czech Republic, belonging to the institution), David POTĚŠIL (203 Czech Republic, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, guarantor, belonging to the institution), Doug CRUMP (124 Canada), Niladri BASU (124 Canada), Natacha HOGAN (124 Canada) and Markus HECKER (124 Canada)

Edition

SCIENCE OF THE TOTAL ENVIRONMENT, NETHERLANDS, ELSEVIER, 2022, 0048-9697

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10511 Environmental sciences

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

fulltext

Impact factor

Impact factor: 9.800

RIV identification code

RIV/00216224:14310/22:00125949

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1016/j.scitotenv.2021.152747

UT WoS

000766818100009

Keywords in English

Fathead minnow Fluoxetine Transcriptomics Proteomics Fecundity Toxicity pathways

Abstract

V originále

Current ecotoxicity testing programs are impeded as they predominantly rely on slow and expensive animal tests measuring adverse outcomes. Therefore, new approach methodologies (NAMs) increasingly involve short-term mechanistic assays that employ molecular endpoints to predict adverse outcomes of regulatory relevance. This study aimed to elucidate the application of NAMs in adult fathead minnows using fluoxetine (FLX) as a model compound. Fish were exposed to three FLX concentrations (measured: 2.42, 10.7, and 56.7 mu gL(-1)) and a control. After 96 h, molecular toxicity signatures were characterized using proteomics and transcriptomics analyses in livers and brains of a sub-set of fish. The remaining fish were sampled at 21 days and assessed for liver histopathology and morphometric measurements. Fecundity was monitored throughout the study. In the livers, 56.7 mu gL(-1) FLX caused enrichment of PPAR signaling in the proteome and fatty acid-related pathways in the transcriptome, potential upstream responses that led to lipid-type vacuolation of hepatocytes, observed via histopathology. Upregulated genes in the brain suggested alterations in serotonin-related signaling processes and reproductive behaviour, which may explain the observed signifi-cant decrease in fecundity. While the relationships between molecular responses and adverse outcomes remain complex, this research provided important insights into the mechanistic toxicity of FLX.

Links

LM2018140, research and development project

Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)

Investor: Ministry of Education, Youth and Sports of the CR

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

90127, large research infrastructures

Name: CIISB II

Citovat

COLVILLE, Carly, Alper James ALCARAZ, Derek GREEN, Bradley PARK, Jianguo XIA, Othman SOUFAN, Pavel HRUŠKA, David POTĚŠIL, Zbyněk ZDRÁHAL, Doug CRUMP, Niladri BASU, Natacha HOGAN and Markus HECKER. Characterizing toxicity pathways of fluoxetine to predict adverse outcomes in adult fathead minnows (Pimephales promelas). SCIENCE OF THE TOTAL ENVIRONMENT. NETHERLANDS: ELSEVIER, 2022, vol. 817, APR, p. "152747", 10 pp. ISSN 0048-9697. Available from: https://dx.doi.org/10.1016/j.scitotenv.2021.152747.

@article{1858732,
   author = {Colville, Carly and Alcaraz, Alper James and Green, Derek and Park, Bradley and Xia, Jianguo and Soufan, Othman and Hruška, Pavel and Potěšil, David and Zdráhal, Zbyněk and Crump, Doug and Basu, Niladri and Hogan, Natacha and Hecker, Markus},
   article_location = {NETHERLANDS},
   article_number = {APR},
   doi = {http://dx.doi.org/10.1016/j.scitotenv.2021.152747},
   keywords = {Fathead minnow Fluoxetine Transcriptomics Proteomics Fecundity Toxicity pathways},
   language = {eng},
   issn = {0048-9697},
   journal = {SCIENCE OF THE TOTAL ENVIRONMENT},
   title = {Characterizing toxicity pathways of fluoxetine to predict adverse outcomes in adult fathead minnows (Pimephales promelas)},
   url = {http://www.sciencedirect.com/science/article/pii/S0048969721078268},
   volume = {817},
   year = {2022}
}

TY  - JOUR
ID  - 1858732
AU  - Colville, Carly - Alcaraz, Alper James - Green, Derek - Park, Bradley - Xia, Jianguo - Soufan, Othman - Hruška, Pavel - Potěšil, David - Zdráhal, Zbyněk - Crump, Doug - Basu, Niladri - Hogan, Natacha - Hecker, Markus
PY  - 2022
TI  - Characterizing toxicity pathways of fluoxetine to predict adverse outcomes in adult fathead minnows (Pimephales promelas)
JF  - SCIENCE OF THE TOTAL ENVIRONMENT
VL  - 817
IS  - APR
SP  - "152747"
EP  - "152747"
PB  - ELSEVIER
SN  - 00489697
KW  - Fathead minnow Fluoxetine Transcriptomics Proteomics Fecundity Toxicity pathways
UR  - http://www.sciencedirect.com/science/article/pii/S0048969721078268
N2  - Current ecotoxicity testing programs are impeded as they predominantly rely on slow and expensive animal tests measuring adverse outcomes. Therefore, new approach methodologies (NAMs) increasingly involve short-term mechanistic assays that employ molecular endpoints to predict adverse outcomes of regulatory relevance. This study aimed to elucidate the application of NAMs in adult fathead minnows using fluoxetine (FLX) as a model compound. Fish were exposed to three FLX concentrations (measured: 2.42, 10.7, and 56.7 mu gL(-1)) and a control. After 96 h, molecular toxicity signatures were characterized using proteomics and transcriptomics analyses in livers and brains of a sub-set of fish. The remaining fish were sampled at 21 days and assessed for liver histopathology and morphometric measurements. Fecundity was monitored throughout the study. In the livers, 56.7 mu gL(-1) FLX caused enrichment of PPAR signaling in the proteome and fatty acid-related pathways in the transcriptome, potential upstream responses that led to lipid-type vacuolation of hepatocytes, observed via histopathology. Upregulated genes in the brain suggested alterations in serotonin-related signaling processes and reproductive behaviour, which may explain the observed signifi-cant decrease in fecundity. While the relationships between molecular responses and adverse outcomes remain complex, this research provided important insights into the mechanistic toxicity of FLX.
ER  -

COLVILLE, Carly, Alper James ALCARAZ, Derek GREEN, Bradley PARK, Jianguo XIA, Othman SOUFAN, Pavel HRUŠKA, David POTĚŠIL, Zbyněk ZDRÁHAL, Doug CRUMP, Niladri BASU, Natacha HOGAN and Markus HECKER. Characterizing toxicity pathways of fluoxetine to predict adverse outcomes in adult fathead minnows (Pimephales promelas). \textit{SCIENCE OF THE TOTAL ENVIRONMENT}. NETHERLANDS: ELSEVIER, 2022, vol.~817, APR, p.~''152747'', 10 pp. ISSN~0048-9697. Available from: https://dx.doi.org/10.1016/j.scitotenv.2021.152747.

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