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Ceftriaxone affects ferroptosis and alleviates glial cell activation in Parkinson's disease

  • Authors:
    • Hui Zhi
    • Xiaoyu Wang
    • Yujia Chen
    • Zenglin Cai
    • Jingwei Li
    • Dongkai Guo
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, Jiangsu 215153, P.R. China, Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu 215002, P.R. China
    Copyright: © Zhi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 85
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    Published online on: April 1, 2025
       https://doi.org/10.3892/ijmm.2025.5526
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Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder, which is characterized by the death of dopaminergic neurons. It has been reported that ceftriaxone (CEF) exerts promising effects on alleviating dopaminergic neuron death in PD models. However, the neuroprotective mechanisms of CEF in PD have not been well understood. In the present study, to investigate the neuroprotective effects of CEF through western blot and immunofluorescence assays, two in vivo models were established, namely the 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP)‑ and lipopolysaccharide (LPS)‑induced models. Additionally, three in vitro models were used to explore the neuroprotective mechanisms of CEF, namely the 1‑methyl‑4‑phenylpyridinium ion (MPP+)‑induced dopaminergic neuron injury, LPS‑induced microglia activation and TNFα‑induced astrocyte activation models, with key insights derived from western blot and qPCR experiments. The in vivo studies demonstrated that CEF exerted neuroprotective effects and reduced glial cell activation. Additionally, CEF reversed the reduction of tyrosine hydroxylase and suppressed the activation of microglia and astrocytes. Furthermore, the in vitro experiments revealed that CEF could display both direct and indirect neuroprotective effects and could directly alleviate MPP+‑induced neuronal toxicity and suppress the activation of microglia and astrocytes. In addition, CEF indirectly reduced neuronal injury caused by conditioned medium from activated microglia and astrocytes. Mechanistic studies revealed that CEF inhibited the ferroptosis pathway via regulating the expression of solute carrier family 7 member 11 and glutathione peroxidase 4 in a non‑cell‑specific manner. Via inhibiting ferroptosis, CEF could directly protect dopaminergic neurons and prevent glial cell activation, and indirectly impair neurons. In conclusion, the results of the current study highlighted the potential research and therapeutic value of CEF in regulating ferroptosis in PD.
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Copy and paste a formatted citation
Spandidos Publications style
Zhi H, Wang X, Chen Y, Cai Z, Li J and Guo D: Ceftriaxone affects ferroptosis and alleviates glial cell activation in Parkinson's disease. Int J Mol Med 55: 85, 2025.
APA
Zhi, H., Wang, X., Chen, Y., Cai, Z., Li, J., & Guo, D. (2025). Ceftriaxone affects ferroptosis and alleviates glial cell activation in Parkinson's disease. International Journal of Molecular Medicine, 55, 85. https://doi.org/10.3892/ijmm.2025.5526
MLA
Zhi, H., Wang, X., Chen, Y., Cai, Z., Li, J., Guo, D."Ceftriaxone affects ferroptosis and alleviates glial cell activation in Parkinson's disease". International Journal of Molecular Medicine 55.6 (2025): 85.
Chicago
Zhi, H., Wang, X., Chen, Y., Cai, Z., Li, J., Guo, D."Ceftriaxone affects ferroptosis and alleviates glial cell activation in Parkinson's disease". International Journal of Molecular Medicine 55, no. 6 (2025): 85. https://doi.org/10.3892/ijmm.2025.5526
Copy and paste a formatted citation
x
Spandidos Publications style
Zhi H, Wang X, Chen Y, Cai Z, Li J and Guo D: Ceftriaxone affects ferroptosis and alleviates glial cell activation in Parkinson's disease. Int J Mol Med 55: 85, 2025.
APA
Zhi, H., Wang, X., Chen, Y., Cai, Z., Li, J., & Guo, D. (2025). Ceftriaxone affects ferroptosis and alleviates glial cell activation in Parkinson's disease. International Journal of Molecular Medicine, 55, 85. https://doi.org/10.3892/ijmm.2025.5526
MLA
Zhi, H., Wang, X., Chen, Y., Cai, Z., Li, J., Guo, D."Ceftriaxone affects ferroptosis and alleviates glial cell activation in Parkinson's disease". International Journal of Molecular Medicine 55.6 (2025): 85.
Chicago
Zhi, H., Wang, X., Chen, Y., Cai, Z., Li, J., Guo, D."Ceftriaxone affects ferroptosis and alleviates glial cell activation in Parkinson's disease". International Journal of Molecular Medicine 55, no. 6 (2025): 85. https://doi.org/10.3892/ijmm.2025.5526
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