Developmental defects induced by thiabendazole are mediated via apoptosis, oxidative stress and alteration in PI3K/Akt and MAPK pathways in zebrafish
Thiabendazole, a benzimidazole fungicide, is widely used to prevent yield loss in agricultural land by inhibiting plant diseases derived from fungi. As thiabendazole has a stable benzimidazole ring structure, it remains in the environment for an extended period, and its toxic effects on non-target o...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2023-06-01
|
Series: | Environment International |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412023002465 |
_version_ | 1797812093105209344 |
---|---|
author | Junho Park Garam An Hahyun Park Taeyeon Hong Whasun Lim Gwonhwa Song |
author_facet | Junho Park Garam An Hahyun Park Taeyeon Hong Whasun Lim Gwonhwa Song |
author_sort | Junho Park |
collection | DOAJ |
description | Thiabendazole, a benzimidazole fungicide, is widely used to prevent yield loss in agricultural land by inhibiting plant diseases derived from fungi. As thiabendazole has a stable benzimidazole ring structure, it remains in the environment for an extended period, and its toxic effects on non-target organisms have been reported, indicating the possibility that it could threaten public health. However, little research has been conducted to elucidate the comprehensive mechanisms of its developmental toxicity. Therefore, we used zebrafish, a representative toxicological model that can predict toxicity in aquatic organisms and mammals, to demonstrate the developmental toxicity of thiabendazole. Various morphological malformations were observed, including decreased body length, eye size, and increased heart and yolk sac edema. Apoptosis, reactive oxygen species (ROS) production, and inflammatory response were also triggered by thiabendazole exposure in zebrafish larvae. Furthermore, PI3K/Akt and MAPK signaling pathways important for appropriate organogenesis were significantly changed by thiabendazole. These results led to toxicity in various organs and a reduction in the expression of related genes, including cardiovascular toxicity, neurotoxicity, and hepatic and pancreatic toxicity, which were detected in flk1:eGFP, olig2:dsRED, and L-fabp:dsRed;elastase:GFP transgenic zebrafish models, respectively. Overall, this study partly determined the developmental toxicity of thiabendazole in zebrafish and provided evidence of the environmental hazards of this fungicide. |
first_indexed | 2024-03-13T07:33:22Z |
format | Article |
id | doaj.art-6755089723314de0b5a2bd14e0e61cfd |
institution | Directory Open Access Journal |
issn | 0160-4120 |
language | English |
last_indexed | 2024-03-13T07:33:22Z |
publishDate | 2023-06-01 |
publisher | Elsevier |
record_format | Article |
series | Environment International |
spelling | doaj.art-6755089723314de0b5a2bd14e0e61cfd2023-06-04T04:23:05ZengElsevierEnvironment International0160-41202023-06-01176107973Developmental defects induced by thiabendazole are mediated via apoptosis, oxidative stress and alteration in PI3K/Akt and MAPK pathways in zebrafishJunho Park0Garam An1Hahyun Park2Taeyeon Hong3Whasun Lim4Gwonhwa Song5Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of KoreaInstitute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of KoreaInstitute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of KoreaDepartment of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of KoreaDepartment of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea; Corresponding authors at: Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea (G. Song); Department of Biological Sciences, College of Science, Sungkyunkwan University, Suwon 16419, Republic of Korea (W. Lim).Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea; Corresponding authors at: Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea (G. Song); Department of Biological Sciences, College of Science, Sungkyunkwan University, Suwon 16419, Republic of Korea (W. Lim).Thiabendazole, a benzimidazole fungicide, is widely used to prevent yield loss in agricultural land by inhibiting plant diseases derived from fungi. As thiabendazole has a stable benzimidazole ring structure, it remains in the environment for an extended period, and its toxic effects on non-target organisms have been reported, indicating the possibility that it could threaten public health. However, little research has been conducted to elucidate the comprehensive mechanisms of its developmental toxicity. Therefore, we used zebrafish, a representative toxicological model that can predict toxicity in aquatic organisms and mammals, to demonstrate the developmental toxicity of thiabendazole. Various morphological malformations were observed, including decreased body length, eye size, and increased heart and yolk sac edema. Apoptosis, reactive oxygen species (ROS) production, and inflammatory response were also triggered by thiabendazole exposure in zebrafish larvae. Furthermore, PI3K/Akt and MAPK signaling pathways important for appropriate organogenesis were significantly changed by thiabendazole. These results led to toxicity in various organs and a reduction in the expression of related genes, including cardiovascular toxicity, neurotoxicity, and hepatic and pancreatic toxicity, which were detected in flk1:eGFP, olig2:dsRED, and L-fabp:dsRed;elastase:GFP transgenic zebrafish models, respectively. Overall, this study partly determined the developmental toxicity of thiabendazole in zebrafish and provided evidence of the environmental hazards of this fungicide.http://www.sciencedirect.com/science/article/pii/S0160412023002465Zebrafish modelThiabendazoleApoptosisOxidative stressSignaling cascade |
spellingShingle | Junho Park Garam An Hahyun Park Taeyeon Hong Whasun Lim Gwonhwa Song Developmental defects induced by thiabendazole are mediated via apoptosis, oxidative stress and alteration in PI3K/Akt and MAPK pathways in zebrafish Environment International Zebrafish model Thiabendazole Apoptosis Oxidative stress Signaling cascade |
title | Developmental defects induced by thiabendazole are mediated via apoptosis, oxidative stress and alteration in PI3K/Akt and MAPK pathways in zebrafish |
title_full | Developmental defects induced by thiabendazole are mediated via apoptosis, oxidative stress and alteration in PI3K/Akt and MAPK pathways in zebrafish |
title_fullStr | Developmental defects induced by thiabendazole are mediated via apoptosis, oxidative stress and alteration in PI3K/Akt and MAPK pathways in zebrafish |
title_full_unstemmed | Developmental defects induced by thiabendazole are mediated via apoptosis, oxidative stress and alteration in PI3K/Akt and MAPK pathways in zebrafish |
title_short | Developmental defects induced by thiabendazole are mediated via apoptosis, oxidative stress and alteration in PI3K/Akt and MAPK pathways in zebrafish |
title_sort | developmental defects induced by thiabendazole are mediated via apoptosis oxidative stress and alteration in pi3k akt and mapk pathways in zebrafish |
topic | Zebrafish model Thiabendazole Apoptosis Oxidative stress Signaling cascade |
url | http://www.sciencedirect.com/science/article/pii/S0160412023002465 |
work_keys_str_mv | AT junhopark developmentaldefectsinducedbythiabendazolearemediatedviaapoptosisoxidativestressandalterationinpi3kaktandmapkpathwaysinzebrafish AT garaman developmentaldefectsinducedbythiabendazolearemediatedviaapoptosisoxidativestressandalterationinpi3kaktandmapkpathwaysinzebrafish AT hahyunpark developmentaldefectsinducedbythiabendazolearemediatedviaapoptosisoxidativestressandalterationinpi3kaktandmapkpathwaysinzebrafish AT taeyeonhong developmentaldefectsinducedbythiabendazolearemediatedviaapoptosisoxidativestressandalterationinpi3kaktandmapkpathwaysinzebrafish AT whasunlim developmentaldefectsinducedbythiabendazolearemediatedviaapoptosisoxidativestressandalterationinpi3kaktandmapkpathwaysinzebrafish AT gwonhwasong developmentaldefectsinducedbythiabendazolearemediatedviaapoptosisoxidativestressandalterationinpi3kaktandmapkpathwaysinzebrafish |