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.

Automated summary

This study investigated the protective mechanisms of curcumin in spleen damage induced by mercury, revealing that curcumin combats autophagic cell death induced by mercury by activating the Nrf2 signaling pathway and inhibiting the PI3K-AKT signaling pathway. This research provides insight into potential pharmacological interventions to prevent spleen injury induced by mercury.