Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 217, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2021.111389
Keywords
Cadmium; Puerarin; Nrf2; Autophagy; NLRP3; Inflammation
Funding
- Chengdu Science and Technology Bureau [2018YFYF00055SN]
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The study found that puerarin can prevent autophagy inhibition and NLRP3 inflammasome activation induced by cadmium by restoring Nrf2 pathway, providing novel insights into the protection of puerarin against cadmium-induced hepatic cell damage.
Liver is the main target organ of cadmium (Cd) toxicity and puerarin (PU) has been shown to prevent Cd-induced hepatic cell damage via its antioxidant activity. Nrf2 acts as a critical regulator of cellular defense against various oxidative insults, but its role in the protection of PU against Cd-induced hepatic damage has not yet been clarified. Hereby, this study was designed to investigate the underlying mechanism using mouse hepatocyte line AML-12. Data firstly showed that Cd-inhibited Nrf2 pathway was markedly restored by PU treatment, assessed by Nrf2 nuclear translocation, protein levels of Keap1 and Nrf2 downstream target genes. Accordingly, Cd-reduced protein levels of antioxidant enzymes were significantly up-regulated by PU. Next, Nrf2 silencing cellular model was established to further elucidate the role of Nrf2 in the protection of PU against Cd-induced hepatic damage. Attenuation of Cd-induced autophagy inhibition and autophagosome accumulation by PU was remarkably countered by Nrf2 silencing. Moreover, alleviation of Cd-induced NLRP3 inflammasome activation by PU was distinctly prevented by Nrf2 knockdown, assessed by protein levels of NLRP3 inflammosome complex and downstream IL-18 and IL-1? production. Collectively, our data suggest that PU restores Cd-induced Nrf2 inhibition to prevent autophagy inhibition and NLRP3 inflammasome activation, providing novel insights into the protection of PU against Cd-induced hepatic cell damage.
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