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Salidroside Alleviates Fluoride-Induced Pyroptosis and Developmental Neurotoxicity Through P2X7R/NF-κB/NLRP3 Pathway
Ya Xia1, Zhiyuan Tian1,2, Yalan Guo1
1School of Public Health, Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 561113, People's Republic of China.
Biological Trace Element Research
|November 20, 2025
Summary
Fluoride exposure damages striatal neurons by activating the P2X7R/NF-κB/NLRP3 pathway, leading to pyroptosis and cognitive decline. Salidroside protects against this neurotoxicity by inhibiting this pathway.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Fluoride neurotoxicity mechanisms are unclear, with limited research on striatal neuron pyroptosis.
- Neuronal pyroptosis is linked to cognitive dysfunction, but studies often overlook the striatum.
Purpose of the Study:
- Investigate if the P2X7R/NF-κB/NLRP3 pathway triggers pyroptosis in striatal neurons, mediating fluoride neurotoxicity.
- Evaluate salidroside's therapeutic potential against fluoride-induced striatal neurotoxicity.
Main Methods:
- Established in vivo (F2 SD rats) and in vitro (NG108-15 cells) models of fluoride exposure with salidroside intervention.
- Assessed neurobehavioral changes using radial arm maze (RAM).
- Analyzed histopathological (HE staining), ultrastructural (TEM), and molecular changes (pyroptosis markers).
Main Results:
- Fluoride exposure caused striatal neuronal degeneration, neurobehavioral deficits, and impaired memory in rats.
- Fluoride activated the P2X7R/NF-κB/NLRP3 pathway, promoting striatal neuron pyroptosis.
- Salidroside treatment mitigated fluoride-induced neuronal damage and pyroptosis by inhibiting the P2X7R/NF-κB/NLRP3 pathway.
Conclusions:
- The P2X7R/NF-κB/NLRP3 signaling pathway mediates fluoride-induced striatal pyroptosis and neurotoxicity.
- Salidroside demonstrates significant neuroprotective effects against fluoride toxicity, highlighting its therapeutic potential.
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