2. Academic Validation
  3. Naringin alleviates fluoride-induced neurological impairment: A focus on the regulation of energy metabolism mediated by mitochondrial permeability transition pore

Naringin alleviates fluoride-induced neurological impairment: A focus on the regulation of energy metabolism mediated by mitochondrial permeability transition pore

  • Sci Total Environ. 2024 Dec 10:955:177073. doi: 10.1016/j.scitotenv.2024.177073.
Yuhui Du 1,  Guoqing Wang 2,  Bin Liu 3,  Meng Guo 4,  Xi Yan 5,  Ming Dou 6,  Fangfang Yu 7,  Yue Ba 8,  Guoyu Zhou 9
Affiliations

Affiliations

  • 1 Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China; School of Water Conservancy Science and Engineering, Zhengzhou University, Zhengzhou, Henan 450001, China. Electronic address: duyuhui@zzu.edu.cn.
  • 2 Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China. Electronic address: wgq1001@gs.zzu.edu.cn.
  • 3 Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China.
  • 4 Wuhan Asia Heart Hospital, Wuhan, Hubei 430000, China.
  • 5 Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan 450001, China.
  • 6 School of Water Conservancy Science and Engineering, Zhengzhou University, Zhengzhou, Henan 450001, China.
  • 7 Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China. Electronic address: yufangfang@zzu.edu.cn.
  • 8 Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China; National Health Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Zhengzhou, Henan 450001, China. Electronic address: byyue@zzu.edu.cn.
  • 9 Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China; National Health Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Zhengzhou, Henan 450001, China. Electronic address: zhouguoyu@zzu.edu.cn.
PMID: 39447898 DOI: 10.1016/j.scitotenv.2024.177073
Abstract

The neurological impairment induced by fluoride is associated with mitochondrial dysfunction. Normal mitochondrial permeability transition pore (mPTP) opening plays a pivotal role in mitochondrial function. However, it remains unclear whether p53-dependent mPTP-related mitochondrial Apoptosis is associated with fluoride-induced neurological impairment, and the alleviation of naringin on those. In vivo, NaF-treated rats had impaired learning and memory abilities, damaged hippocampal structure, and higher respiratory exchange rates (RER). In vitro, the increased Apoptosis rates, excessive opening of mPTP, and decreased mitochondrial membrane potential (MMP) were observed in PC12 cells treated with NaF. The protein expressions of p53, CytoC, and cleaved Caspase 3 were significantly increased in hippocampi of rats treated with 50 mg/L and 100 mg/L NaF and in 40 mg/L and 80 mg/L NaF-treated PC12 cells, while the protein expression of CypD remains stable. And the changes of p53 and CypD were also confirmed by the immunofluorescence staining in vivo. After inhibiting the expression of p53 with pifithrin-α and p53-siRNA, the decreased Apoptosis rates and mPTP opening, increased MMP, and decreased protein expressions of p53, CytoC, and cleaved Caspase 3 were observed in NaF-treated PC12 cells. Rats, treated with NaF and naringin, had alleviated impaired neurological function, and had lower RER than rats treated with NaF alone. And compared with those in the NaF group, the decreased Apoptosis rates and mPTP opening, and increased MMP were also found in PC12 cells treated with NaF and naringin. Furthermore, hippocampi of rats and PC12 cells treated with NaF and naringin had decreased protein expressions of p53, CytoC, and cleaved Caspase 3. Our results indicate that fluoride activates the p53-dependent mPTP-related mitochondrial Apoptosis, which then affects energy metabolism, resulting in neurological impairment. Additionally, naringin can alleviate this damage, and further studies on the potential health benefits of naringin are needed.

Keywords

Energy metabolism; Fluoride; Naringin; mPTP; p53.

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