Chronic exposure to environmental concentrations of 6PPDQ induces neurotoxicity via perturbing multiple neurotransmission pathways in zebrafish
Previous research has demonstrated acute toxicity of 6PPD-quinone (6PPDQ), the ozonation product of tire-manufacturing additive 6PPD; however, chronic effects on aquatic organisms under real-world conditions remain unclear. We exposed 2-month-old zebrafish to 6PPDQ at concentrations of 2, 20 and 200...
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Elsevier
2025-07-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412025003307 |
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| author | Chuan Yi Chunyan Xu Pan Gao Hengtao Wang Yao Dang Song Hou Ruowen Zhang Mingdeng Xiang |
| author_facet | Chuan Yi Chunyan Xu Pan Gao Hengtao Wang Yao Dang Song Hou Ruowen Zhang Mingdeng Xiang |
| author_sort | Chuan Yi |
| collection | DOAJ |
| description | Previous research has demonstrated acute toxicity of 6PPD-quinone (6PPDQ), the ozonation product of tire-manufacturing additive 6PPD; however, chronic effects on aquatic organisms under real-world conditions remain unclear. We exposed 2-month-old zebrafish to 6PPDQ at concentrations of 2, 20 and 200 µg/L for 30 days.Whole-body desorption electrospray ionization–mass spectrometry (DESI–MS) revealed accumulation mainly in the muscle, abdomen, and brain of zebrafish exposed to 200 µg/L 6PPDQ, which was verified by MS quantification of muscle and brain tissues. Based on velocity and distance moved, 2 µg/L 6PPDQ induced zebrafish hyperactivity, whereas 20 and 200 µg/L significantly inhibited activity. H&E staining revealed that chronic exposure to 6PPDQ caused brain damage in zebrafish, characterized by vacuolation and ventriculomegaly. Transcriptomic analyses indicated that 6PPDQ exposure disturbed neuron-related signaling pathways, especially glutamatergic/GABAergic, dopaminergic, cholinergic, and serotoninergic pathways. Downregulation of genes related to neurotransmission pathways was noted following exposure to 200 µg/L 6PPDQ. Reduced neurotransmitters, serotonin, 5-hydroxyindolacetic acid, dopamine, γ-aminobutyric acid, glutamate, acetylcholinesterase, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels were also observed after 20 µg/L 6PPDQ exposure. Here, prolonged exposure to environmentally relevant concentrations of 6PPDQ induced neurotoxicity in zebrafish, and the neurotransmission system may be central to this process. These findings may help identify acceptable levels of aquatic 6PPDQ. |
| format | Article |
| id | doaj-art-fe972c57a0a04b2494bf34e0657fd0a7 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
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| series | Environment International |
| spelling | doaj-art-fe972c57a0a04b2494bf34e0657fd0a72025-08-20T03:30:49ZengElsevierEnvironment International0160-41202025-07-0120110957910.1016/j.envint.2025.109579Chronic exposure to environmental concentrations of 6PPDQ induces neurotoxicity via perturbing multiple neurotransmission pathways in zebrafishChuan Yi0Chunyan Xu1Pan Gao2Hengtao Wang3Yao Dang4Song Hou5Ruowen Zhang6Mingdeng Xiang7Hubei Key Laboratory of Pollution Damage Assessment and Environmental Health Risk Prevention and Control, Hubei Academy of Ecological and Environmental Sciences, Wuhan 430072, PR China; Corresponding author at: Hubei Academy of Ecological and Environmental Sciences, Wuhan 430072, China.Hubei Key Laboratory of Pollution Damage Assessment and Environmental Health Risk Prevention and Control, Hubei Academy of Ecological and Environmental Sciences, Wuhan 430072, PR China; School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR ChinaHubei Key Laboratory of Pollution Damage Assessment and Environmental Health Risk Prevention and Control, Hubei Academy of Ecological and Environmental Sciences, Wuhan 430072, PR ChinaHubei Key Laboratory of Pollution Damage Assessment and Environmental Health Risk Prevention and Control, Hubei Academy of Ecological and Environmental Sciences, Wuhan 430072, PR ChinaState Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510655, PR ChinaHubei Key Laboratory of Pollution Damage Assessment and Environmental Health Risk Prevention and Control, Hubei Academy of Ecological and Environmental Sciences, Wuhan 430072, PR ChinaHubei Key Laboratory of Pollution Damage Assessment and Environmental Health Risk Prevention and Control, Hubei Academy of Ecological and Environmental Sciences, Wuhan 430072, PR ChinaState Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510655, PR ChinaPrevious research has demonstrated acute toxicity of 6PPD-quinone (6PPDQ), the ozonation product of tire-manufacturing additive 6PPD; however, chronic effects on aquatic organisms under real-world conditions remain unclear. We exposed 2-month-old zebrafish to 6PPDQ at concentrations of 2, 20 and 200 µg/L for 30 days.Whole-body desorption electrospray ionization–mass spectrometry (DESI–MS) revealed accumulation mainly in the muscle, abdomen, and brain of zebrafish exposed to 200 µg/L 6PPDQ, which was verified by MS quantification of muscle and brain tissues. Based on velocity and distance moved, 2 µg/L 6PPDQ induced zebrafish hyperactivity, whereas 20 and 200 µg/L significantly inhibited activity. H&E staining revealed that chronic exposure to 6PPDQ caused brain damage in zebrafish, characterized by vacuolation and ventriculomegaly. Transcriptomic analyses indicated that 6PPDQ exposure disturbed neuron-related signaling pathways, especially glutamatergic/GABAergic, dopaminergic, cholinergic, and serotoninergic pathways. Downregulation of genes related to neurotransmission pathways was noted following exposure to 200 µg/L 6PPDQ. Reduced neurotransmitters, serotonin, 5-hydroxyindolacetic acid, dopamine, γ-aminobutyric acid, glutamate, acetylcholinesterase, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels were also observed after 20 µg/L 6PPDQ exposure. Here, prolonged exposure to environmentally relevant concentrations of 6PPDQ induced neurotoxicity in zebrafish, and the neurotransmission system may be central to this process. These findings may help identify acceptable levels of aquatic 6PPDQ.http://www.sciencedirect.com/science/article/pii/S01604120250033076PPDQZebrafishMass spectrometry imagingNeurotoxicityNeurotransmitterMolecular mechanism |
| spellingShingle | Chuan Yi Chunyan Xu Pan Gao Hengtao Wang Yao Dang Song Hou Ruowen Zhang Mingdeng Xiang Chronic exposure to environmental concentrations of 6PPDQ induces neurotoxicity via perturbing multiple neurotransmission pathways in zebrafish Environment International 6PPDQ Zebrafish Mass spectrometry imaging Neurotoxicity Neurotransmitter Molecular mechanism |
| title | Chronic exposure to environmental concentrations of 6PPDQ induces neurotoxicity via perturbing multiple neurotransmission pathways in zebrafish |
| title_full | Chronic exposure to environmental concentrations of 6PPDQ induces neurotoxicity via perturbing multiple neurotransmission pathways in zebrafish |
| title_fullStr | Chronic exposure to environmental concentrations of 6PPDQ induces neurotoxicity via perturbing multiple neurotransmission pathways in zebrafish |
| title_full_unstemmed | Chronic exposure to environmental concentrations of 6PPDQ induces neurotoxicity via perturbing multiple neurotransmission pathways in zebrafish |
| title_short | Chronic exposure to environmental concentrations of 6PPDQ induces neurotoxicity via perturbing multiple neurotransmission pathways in zebrafish |
| title_sort | chronic exposure to environmental concentrations of 6ppdq induces neurotoxicity via perturbing multiple neurotransmission pathways in zebrafish |
| topic | 6PPDQ Zebrafish Mass spectrometry imaging Neurotoxicity Neurotransmitter Molecular mechanism |
| url | http://www.sciencedirect.com/science/article/pii/S0160412025003307 |
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