Pentachloronitrobenzene Reduces the Proliferative Capacity of Zebrafish Embryonic Cardiomyocytes via Oxidative Stress

Pentachloronitrobenzene (PCNB) is an organochlorine protective fungicide mainly used as a soil and seed fungicide. Currently, there are few reports on the toxicity of PCNB to zebrafish embryo. Here, we evaluated the toxicity of PCNB in aquatic vertebrates using a zebrafish model. Exposure of zebrafi...

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Main Authors: Guoqiang Fan, Tianzhu Shen, Kun Jia, Xiaoping Xiao, Zhanfeng Wu, Fanghua Gong, Huiqiang Lu
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Toxics
Subjects:
Online Access:https://www.mdpi.com/2305-6304/10/6/299
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author Guoqiang Fan
Tianzhu Shen
Kun Jia
Xiaoping Xiao
Zhanfeng Wu
Fanghua Gong
Huiqiang Lu
author_facet Guoqiang Fan
Tianzhu Shen
Kun Jia
Xiaoping Xiao
Zhanfeng Wu
Fanghua Gong
Huiqiang Lu
author_sort Guoqiang Fan
collection DOAJ
description Pentachloronitrobenzene (PCNB) is an organochlorine protective fungicide mainly used as a soil and seed fungicide. Currently, there are few reports on the toxicity of PCNB to zebrafish embryo. Here, we evaluated the toxicity of PCNB in aquatic vertebrates using a zebrafish model. Exposure of zebrafish embryos to PCNB at concentrations of 0.25 mg/L, 0.5 mg/L, and 0.75 mg/L from 6 hpf to 72 hpf resulted in abnormal embryonic development, including cardiac malformation, pericardial edema, decreased heart rate, decreased blood flow velocity, deposition at yolk sac, shortened body length, and increased distance between venous sinus and arterial bulb (SV-BA). The expression of genes related to cardiac development was disordered. However, due to the unstable embryo status in the 0.75 mg/L exposure concentration group, the effect of PCNB on the expression levels of cardiac-related genes was not concentration-dependent. We found that PCNB increased reactive oxygen species stress levels in zebrafish, increased malondialdehyde (MDA) content and catalase (CAT) activity, and decreased superoxide dismutase (SOD) activity. The increased level of oxidative stress reduced the proliferation ability of zebrafish cardiomyocytes, and the expressions of zebrafish proliferation-related genes such as <i>cdk-2</i>, <i>cdk-6</i>, <i>ccnd1</i>, and <i>ccne1</i> were significantly down-regulated. Astaxanthin (AST) attenuates PCNB-induced reduction in zebrafish cardiomyocyte proliferation by reducing oxidative stress levels. Our study shows that PCNB can cause severe oxidative stress in zebrafish, thereby reducing the proliferative capacity of cardiomyocytes, resulting in zebrafish cardiotoxicity.
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spelling doaj.art-065815697a924497b0c19de0a01506452023-11-23T19:15:56ZengMDPI AGToxics2305-63042022-06-0110629910.3390/toxics10060299Pentachloronitrobenzene Reduces the Proliferative Capacity of Zebrafish Embryonic Cardiomyocytes via Oxidative StressGuoqiang Fan0Tianzhu Shen1Kun Jia2Xiaoping Xiao3Zhanfeng Wu4Fanghua Gong5Huiqiang Lu6School of Pharmacy, Wenzhou Medical University, Wenzhou 325000, ChinaSchool of Pharmacy, Wenzhou Medical University, Wenzhou 325000, ChinaCenter for Drug Screening and Research, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou 341000, ChinaCenter for Drug Screening and Research, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou 341000, ChinaInstitute of Chemistry, Chinese Academy of Sciences, Beijing 100000, ChinaSchool of Pharmacy, Wenzhou Medical University, Wenzhou 325000, ChinaSchool of Pharmacy, Wenzhou Medical University, Wenzhou 325000, ChinaPentachloronitrobenzene (PCNB) is an organochlorine protective fungicide mainly used as a soil and seed fungicide. Currently, there are few reports on the toxicity of PCNB to zebrafish embryo. Here, we evaluated the toxicity of PCNB in aquatic vertebrates using a zebrafish model. Exposure of zebrafish embryos to PCNB at concentrations of 0.25 mg/L, 0.5 mg/L, and 0.75 mg/L from 6 hpf to 72 hpf resulted in abnormal embryonic development, including cardiac malformation, pericardial edema, decreased heart rate, decreased blood flow velocity, deposition at yolk sac, shortened body length, and increased distance between venous sinus and arterial bulb (SV-BA). The expression of genes related to cardiac development was disordered. However, due to the unstable embryo status in the 0.75 mg/L exposure concentration group, the effect of PCNB on the expression levels of cardiac-related genes was not concentration-dependent. We found that PCNB increased reactive oxygen species stress levels in zebrafish, increased malondialdehyde (MDA) content and catalase (CAT) activity, and decreased superoxide dismutase (SOD) activity. The increased level of oxidative stress reduced the proliferation ability of zebrafish cardiomyocytes, and the expressions of zebrafish proliferation-related genes such as <i>cdk-2</i>, <i>cdk-6</i>, <i>ccnd1</i>, and <i>ccne1</i> were significantly down-regulated. Astaxanthin (AST) attenuates PCNB-induced reduction in zebrafish cardiomyocyte proliferation by reducing oxidative stress levels. Our study shows that PCNB can cause severe oxidative stress in zebrafish, thereby reducing the proliferative capacity of cardiomyocytes, resulting in zebrafish cardiotoxicity.https://www.mdpi.com/2305-6304/10/6/299pentachloronitrobenzenepericardial edemareactive oxygen speciesproliferation of cardiomyocyteszebrafish
spellingShingle Guoqiang Fan
Tianzhu Shen
Kun Jia
Xiaoping Xiao
Zhanfeng Wu
Fanghua Gong
Huiqiang Lu
Pentachloronitrobenzene Reduces the Proliferative Capacity of Zebrafish Embryonic Cardiomyocytes via Oxidative Stress
Toxics
pentachloronitrobenzene
pericardial edema
reactive oxygen species
proliferation of cardiomyocytes
zebrafish
title Pentachloronitrobenzene Reduces the Proliferative Capacity of Zebrafish Embryonic Cardiomyocytes via Oxidative Stress
title_full Pentachloronitrobenzene Reduces the Proliferative Capacity of Zebrafish Embryonic Cardiomyocytes via Oxidative Stress
title_fullStr Pentachloronitrobenzene Reduces the Proliferative Capacity of Zebrafish Embryonic Cardiomyocytes via Oxidative Stress
title_full_unstemmed Pentachloronitrobenzene Reduces the Proliferative Capacity of Zebrafish Embryonic Cardiomyocytes via Oxidative Stress
title_short Pentachloronitrobenzene Reduces the Proliferative Capacity of Zebrafish Embryonic Cardiomyocytes via Oxidative Stress
title_sort pentachloronitrobenzene reduces the proliferative capacity of zebrafish embryonic cardiomyocytes via oxidative stress
topic pentachloronitrobenzene
pericardial edema
reactive oxygen species
proliferation of cardiomyocytes
zebrafish
url https://www.mdpi.com/2305-6304/10/6/299
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