Academic Journal
Pyrethrin II impairs mitochondrial potential through ROS and MAPK pathways in HT‑22 cells.
| Τίτλος: | Pyrethrin II impairs mitochondrial potential through ROS and MAPK pathways in HT‑22 cells. |
|---|---|
| Συγγραφείς: | Gao J; Department of Biological and Food Engineering, Lyuliang University, Lvliang, Shanxi 033001, China., Zhang X; Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China., Mu Q; Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China., Liu Y; Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China., Yang H; Department of Hepatobiliary Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China., Cao R; Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China., Wang X; Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China., Yu B; Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China. Electronic address: shanxiyangcheng@126.com., Zhang L; Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Department of Hepatobiliary Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China. Electronic address: zhangli3788@163.com., Guo Y; Department of Pain Management, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan 030032, China. Electronic address: guoyaoyao@sxbqeh.com.cn. |
| Πηγή: | Neurotoxicology [Neurotoxicology] 2026 Sep; Vol. 116, pp. 103518. Date of Electronic Publication: 2026 Jul 13. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 7905589 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9711 (Electronic) Linking ISSN: 0161813X NLM ISO Abbreviation: Neurotoxicology Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2001- : Amsterdam : Elsevier Science Original Publication: Park Forest South, Ill., Pathotox Publishers. |
| Ιατρικοί όροι (MeSH): | Reactive Oxygen Species*/metabolism , Membrane Potential, Mitochondrial*/drug effects , Pyrethrins*/toxicity , MAP Kinase Signaling System*/drug effects , MAP Kinase Signaling System*/physiology , Insecticides*/toxicity , Neurons*/drug effects , Neurons*/metabolism, Apoptosis/drug effects ; Cell Survival/drug effects ; Cell Proliferation/drug effects ; Mitochondria/drug effects ; Animals ; Cell Line ; Mice ; Dose-Response Relationship, Drug |
| Περίληψη: | Objective: Pyrethrin II, a key active monomer of natural pyrethrins, is widely used in household insecticides. This study investigated whether Pyrethrin II induces hippocampal neuronal injury through ROS overproduction and MAPK pathway dysregulation. Methods: HT-22 cells were treated with Pyrethrin II at concentrations of 10 and 40 μg/mL for 24 h. Subsequently, cell viability was evaluated using the CCK-8 assay, transcriptomic sequencing was performed to identify global transcriptional changes, intracellular ROS levels were measured by flow cytometry, MAPK pathway protein expression was analyzed via Western blotting, mitochondrial membrane potential was assessed with JC-1 staining, apoptosis was determined by TUNEL staining and cleaved caspase-3 levels, and cell proliferation was examined using EdU incorporation and PCNA expression. Results: Transcriptomic analysis revealed dose-dependent transcriptional alterations, with the MAPK pathway identified as the core toxic mechanism. Pyrethrin II induced excessive ROS production, which activated JNK and p38 but suppressed ERK1/2. The ROS inhibitor NAC partially reversed these effects. JNK activation decreased mitochondrial membrane potential and triggered compensatory mitochondrial biogenesis (upregulated TOMM20). ERK suppression reduced cell proliferation, which was partially restored by the ERK activator TPA. JNK activation promoted apoptosis (increased cleaved caspase-3 and TUNEL‑positive cells), an effect attenuated by the JNK inhibitor SP600126. Conclusion: Pyrethrin II disrupts the proliferation-apoptosis balance by inducing ROS overproduction, suppressing ERK, and activating JNK/p38, leading to mitochondrial dysfunction and neuronal injury. Our findings identify the ROS‑mediated JNK/ERK axis as a key mechanism of its in vitro neurotoxicity. However, given the essential physiological functions of JNK and ERK, direct targeting may cause systemic side effects. Future studies should explore upstream or more selective modulators to avoid disrupting normal cellular functions. (Copyright © 2026. Published by Elsevier B.V.) |
| Competing Interests: | Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Li Zhang reports financial support was provided by National Natural Science Foundation of China (Grant No. 82201319). Jiaojiao Gao reports financial support was provided by Fundamental Research Program of Shanxi Province (Grant Nos. 202403021212086, 202503021212332, 202503021212256). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: MAPK signaling pathway; Mitochondrial function; Pyrethrin II; Reactive oxygen species |
| Substance Nomenclature: | 0 (Reactive Oxygen Species) 0 (Pyrethrins) 0 (Insecticides) |
| Entry Date(s): | Date Created: 20260713 Date Completed: 20260909 Latest Revision: 20260909 |
| Update Code: | 20260910 |
| DOI: | 10.1016/j.neuro.2026.103518 |
| PMID: | 42442637 |
| Βάση Δεδομένων: | MEDLINE |
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