Antagonizing effects of curcumin against mercury-induced autophagic death and trace elements disorder by regulating PI3K/AKT and Nrf2 pathway in the spleen

Mercury is a naturally occurring element and highly toxic to humans even at a low dosage. Curcumin is a polyphenol found in turmeric (Curcuma longa), widely used as a treatment strategy to improve antioxidant and anti-inflammatory properties. The purpose of this study was to investigate the potential protective mechanisms of curcumin in spleen damage induced by HgCl₂. The mice were given curcumin by intragastric administration 2 h before HgCl₂ injection for 24 h. At first, splenic transcriptome analysis showed that 3334 genes (2134 up and 1200 down) were differently expressed in HgCl₂-induced spleen damage model. Notably, KEGG enrichment showed phosphatidylinositol 3-kinase (PI3K)-AKT might be a key signaling pathways in HgCl₂-induced spleen damage. Furthermore, our data demonstrated that HgCl₂ could induce autophagic cell death, evidenced by increases the protein expression of PI3K, Akt, LC3-II and p62 and the number of apoptotic cells. Furthermore, we found that curcumin significantly combated autophagic cell death, sodium overload and calcium leak induced by HgCl₂. Simultaneously, further studies demonstrated that curcumin significantly activated nuclear factor (erythroid-derived-2)-like 2 (Nrf2) signaling pathway, and subsequent enhancing antioxidant defenses. Taken together, our data indicated that inorganic mercury could result in autophagic cell death, which may be related to the regulation of PI3K-AKT signaling cascades. Furthermore, Nrf2-mediated antioxidant defenses may be the target of curcumin to confers an adaptive survival response to resist spleen damage induced by HgCl₂. The present study perfects the mechanism theory of HgCl₂-induced spleen damage and provides a way for pharmacological intervention to prevent spleen injury.