Thallium-induced neurocardiotoxicity in zebrafish: Protective role of adaptive UPR and DNA repair.
Journal
Ecotoxicology and environmental safety
Journal Volume
298
Start Page
Article number 118321
ISSN
1090-2414
Date Issued
2025-06-15
Author(s)
Abstract
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.
Subjects
Adaptive UPR
DNA repair
Embryonic zebrafish model
IXA4
Thallium
Transcriptomic profiling
SDGs
Publisher
Academic Press
Type
journal article