Thallium-induced neurocardiotoxicity in zebrafish: Protective role of adaptive UPR and DNA repair
Thallium (Tl) is a hazardous heavy metal widely used in industrial applications, leading to significant environmental contamination. Tl concentrations in surface waters can reach up to 1520 μg/L, exceeding safe limits and posing risks to aquatic ecosystems and human health. Monovalent thallium [Tl(I...
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Elsevier
2025-06-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325006578 |
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| author | Yung Chang Chia-Hsien Wu Jia-Huang Chen Tsuyoshi Inoue Chih-Kang Chiang |
| author_facet | Yung Chang Chia-Hsien Wu Jia-Huang Chen Tsuyoshi Inoue Chih-Kang Chiang |
| author_sort | Yung Chang |
| collection | DOAJ |
| description | Thallium (Tl) is a hazardous heavy metal widely used in industrial applications, leading to significant environmental contamination. Tl concentrations in surface waters can reach up to 1520 μg/L, exceeding safe limits and posing risks to aquatic ecosystems and human health. Monovalent thallium [Tl(I)] is highly stable and bioaccumulative, readily accumulating in aquatic organisms, plants, and the human food chain. Exposure to Tl has been associated with neurotoxicity, kidney dysfunction, and cardiovascular diseases, particularly affecting children and pregnant women, and may increase the risk of neurodegenerative diseases and cardiac arrhythmias. However, effective strategies to mitigate Tl toxicity remain lacking. This study establishes a zebrafish embryo model to investigate the toxicological mechanisms of Tl and evaluate the protective effects of IXA4, a selective XBP1 activator. Our results show that Tl exposure increases mortality, reduces hatching rates, impairs swim bladder development, and causes pericardial edema and brain abnormalities. Transcriptomic and qPCR analyses confirm that Tl induces endoplasmic reticulum (ER) stress and activates the unfolded protein response (UPR), key pathways involved in cellular toxicity. Co-treatment with IXA4 significantly improves survival rates and developmental outcomes by upregulating DNA repair genes, particularly in the nucleotide excision repair (NER) pathway, thereby reducing cardiac and neural damage. This study provides novel insights into the mechanisms of Tl toxicity, underscores the urgent need for stricter regulatory measures, and highlights IXA4 as a potential intervention for mitigating heavy metal toxicity in aquatic ecosystems. |
| format | Article |
| id | doaj-art-934f134ef6614989934b4605fbd8a6a2 |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-934f134ef6614989934b4605fbd8a6a22025-08-20T03:13:29ZengElsevierEcotoxicology and Environmental Safety0147-65132025-06-0129811832110.1016/j.ecoenv.2025.118321Thallium-induced neurocardiotoxicity in zebrafish: Protective role of adaptive UPR and DNA repairYung Chang0Chia-Hsien Wu1Jia-Huang Chen2Tsuyoshi Inoue3Chih-Kang Chiang4Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, JapanGraduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, JapanGraduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan; Correspondence to: Graduate Institute of Toxicology,College of Medicine, National Taiwan University, No. 1, Section 1, Ren'ai Rd., Taipei City 100233, Taiwan.Thallium (Tl) is a hazardous heavy metal widely used in industrial applications, leading to significant environmental contamination. Tl concentrations in surface waters can reach up to 1520 μg/L, exceeding safe limits and posing risks to aquatic ecosystems and human health. Monovalent thallium [Tl(I)] is highly stable and bioaccumulative, readily accumulating in aquatic organisms, plants, and the human food chain. Exposure to Tl has been associated with neurotoxicity, kidney dysfunction, and cardiovascular diseases, particularly affecting children and pregnant women, and may increase the risk of neurodegenerative diseases and cardiac arrhythmias. However, effective strategies to mitigate Tl toxicity remain lacking. This study establishes a zebrafish embryo model to investigate the toxicological mechanisms of Tl and evaluate the protective effects of IXA4, a selective XBP1 activator. Our results show that Tl exposure increases mortality, reduces hatching rates, impairs swim bladder development, and causes pericardial edema and brain abnormalities. Transcriptomic and qPCR analyses confirm that Tl induces endoplasmic reticulum (ER) stress and activates the unfolded protein response (UPR), key pathways involved in cellular toxicity. Co-treatment with IXA4 significantly improves survival rates and developmental outcomes by upregulating DNA repair genes, particularly in the nucleotide excision repair (NER) pathway, thereby reducing cardiac and neural damage. This study provides novel insights into the mechanisms of Tl toxicity, underscores the urgent need for stricter regulatory measures, and highlights IXA4 as a potential intervention for mitigating heavy metal toxicity in aquatic ecosystems.http://www.sciencedirect.com/science/article/pii/S0147651325006578ThalliumEmbryonic zebrafish modelAdaptive UPRIXA4Transcriptomic profilingDNA repair |
| spellingShingle | Yung Chang Chia-Hsien Wu Jia-Huang Chen Tsuyoshi Inoue Chih-Kang Chiang Thallium-induced neurocardiotoxicity in zebrafish: Protective role of adaptive UPR and DNA repair Ecotoxicology and Environmental Safety Thallium Embryonic zebrafish model Adaptive UPR IXA4 Transcriptomic profiling DNA repair |
| title | Thallium-induced neurocardiotoxicity in zebrafish: Protective role of adaptive UPR and DNA repair |
| title_full | Thallium-induced neurocardiotoxicity in zebrafish: Protective role of adaptive UPR and DNA repair |
| title_fullStr | Thallium-induced neurocardiotoxicity in zebrafish: Protective role of adaptive UPR and DNA repair |
| title_full_unstemmed | Thallium-induced neurocardiotoxicity in zebrafish: Protective role of adaptive UPR and DNA repair |
| title_short | Thallium-induced neurocardiotoxicity in zebrafish: Protective role of adaptive UPR and DNA repair |
| title_sort | thallium induced neurocardiotoxicity in zebrafish protective role of adaptive upr and dna repair |
| topic | Thallium Embryonic zebrafish model Adaptive UPR IXA4 Transcriptomic profiling DNA repair |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325006578 |
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