ArticleJournal of applied toxicology : JAT2022
Caffeine-induced neurotoxicity mediated by Nrf2 pathway in PC12 cells and zebrafish larvae.
Article in Journal of applied toxicology : JAT, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 13 citations in OpenAlex.
- Caffeine Biotransformation in Zebrafish Larvae: Integrated LC-MS/MS Quantification and FTIR Spatial Mapping.Molecules (Basel, Switzerland) · 2026Article
- Machine learning enables high-throughput, low-replicate screening for novel anti-seizure targets and compounds using combined movement and calcium fluorescence in larval zebrafish.European journal of pharmacology · 2025Article
- Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans: an overview of recent findings.Neural regeneration research · 2024Article
- Evaluating the Neuroprotective Potential of Caffeinated Coffee in the Context of Aluminum-Induced Neurotoxicity: Insights from a PC12 Cell Culture Model.Antioxidants (Basel, Switzerland) · 2024Article
- Ferroptosis contributes to hemolytic hyperbilirubinemia‑induced brain damage in vivo and in vitro.Molecular medicine reports · 2023Article
- Article
- Therapy of traumatic brain injury by modern agents and traditional Chinese medicine.Chinese medicine · 2023Review
- Temperature- and chemical-induced neurotoxicity in zebrafish.Frontiers in physiology · 2023Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
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Abstract
Caffeine is one of the most widely used psychostimulants in the world and possesses central excitative, anti-depressive, and neuroprotective properties. However, excessive ingestion or abuse of caffeine can lead to intoxication. Many toxic effects are attributed to oxidative damage, and nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical intracellular regulator of the oxidative stress response. Here, we investigated the neurotoxicity of caffeine in rat pheochromocytoma PC12 cells and zebrafish larvae. It was found that caffeine inhibited the viability of PC12 cells in a dose- and time-dependent manner. Furthermore, it induced PC12 cell apoptosis and elevated reactive oxygen species (ROS) production. Quantitative polymerase chain reaction (qPCR) and western blotting revealed that caffeine also inhibited the expression levels of Nrf2 mRNA and protein and its target genes (e.g., NADPH quinone oxidoreductase 1 [NQO1]). Furthermore, Nrf2 silencing attenuated the toxic effects of caffeine. In addition, zebrafish larvae were treated with different doses of caffeine. Behavioral experiments showed that a low dose of caffeine (0.05 to 0.3 mM) increased the average distance of movement and promoted excitation. Survivorship curves showed that caffeine (0.2 to 1.5 mM) caused lethality. Finally, qPCR revealed that a higher dose of caffeine inhibited mRNA levels in the Nrf2 pathway. Based on these results, this study identified for the first time that overuse of caffeine can induce neurotoxicity by inhibiting the Nrf2 pathway. These results will provide a new perspective for studies on caffeine toxicity.
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