Nrf2/PINK1-mediated mitophagy induction alleviates sodium fluoride-induced hepatic injury by improving mitochondrial function, oxidative stress, and inflammation

Mitophagy has distinct functions, which can lead to either protection or damage of tissues. Though current evidence indicated that NaF triggers mitophagy, the role and regulation of mitophagy in sodium fluoride (NaF)-induced liver injury still remain unclear. Therefore, we exployed the cell and mous...

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Veröffentlicht in:Ecotoxicology and environmental safety 2023-03, Vol.252, p.114646-114646, Article 114646
Hauptverfasser: Song, Chao, Zhang, Aiguo, Zhang, Man, Song, Yuzhen, Huangfu, Heping, Jin, Shuangxing, Sun, Yanting, Zhang, Chunhui, Shi, Dongmei, Wang, Jundong, Peng, Wei, Luo, Qin
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Sprache:eng
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Zusammenfassung:Mitophagy has distinct functions, which can lead to either protection or damage of tissues. Though current evidence indicated that NaF triggers mitophagy, the role and regulation of mitophagy in sodium fluoride (NaF)-induced liver injury still remain unclear. Therefore, we exployed the cell and mouse models and confirmed that NaF treatment activates mitophagy. Knocking down PTEN-induced putative kinase protein 1 (PINK1) expression attenuated mitophagy and increased the degree of mitochondrial impairment, oxidative stress, and apoptosis in NaF-treated HepG2 cells. In vivo experiments indicated that PINK1 deficiency weakened NaF-induced mitophagy. Moreover, PINK1-deficient mices aggravated NaF-induced hepatic mitochondrial injury, oxidative stress, and inflammation in livers, evidenced by the increased number of abnormal mitochondria, decreased adenosine triphosphate (ATP) and glutathione (GSH) levels, elevated reactive oxygen species (ROS) and malondialdehyde (MDA) content, enhanced hepatic macrophage infiltration and inflammatory cytokine levels. Notably, NaF exposure activated Nrf2 signaling both in vitro and in vivo. Nrf2 siRNA transfection blocked the upregulation of PINK1 expression and the induction of mitophagy in NaF-treated HepG2 cells. Also, ML385 (Nrf2 inhibitor) partially blocked the upregulation of PINK1 expression caused by NaF in mice livers. To sum up, the present study provided the demonstration that Nrf2/PINK1-mediated mitophagy activation offers a hepatoprotective effect by inhibiting NaF-induced mitochondrial dysfunction, oxidative stress, and inflammation. [Display omitted] •NaF-induced mitophagy activation is regulated by PINK1/Parkin signaling.•Mitophagy induction alleviates NaF-induced mitochondrial impairment.•Mitophagy inhibition aggravates NaF-induced oxidative stress and apoptosis.•Mitophagy induction ameliorates inflammation caused by NaF.•Nrf2 triggers PINK1 expression under NaF stimulation.
ISSN:0147-6513
1090-2414
DOI:10.1016/j.ecoenv.2023.114646