Curcumin prevents cadmium or H2O2-induced oxidative stress via Nrf2/ARE signaling and autophagy in myeloid cells

The evidence linking high levels of environmental pollutants to chronic degenerative diseases is alarming, with heavy metals (HM) identified as a key factor. Research suggests that certain phytochemicals in the diet can reduce HM levels and mitigate their adverse health effects.Curcumin (Curc), a natural polyphenol, is particularly effective in protecting against Cadmium (Cd) toxicity. The present study demonstrates that preincubation with low doses of Curc (1 μM) in differentiated HL-60 and K-562 human myeloid cells can significantly protect against cytotoxicity induced by Cd and or hydrogen peroxide (H₂O₂). Curc reduced the increased levels of Reactive Oxygen Species (ROS) generated by Cd or H₂O₂ by inducing a protective form of autophagy, a relevant process for the cellular homeostasis. Curc activated mild oxidative stress that triggers the expression of Nrf2-dependent transcripts, such as Nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent transcripts, such as human NADPH Quinone Oxidoreductase 1 (NQO1) and Heme Oxygenase (HO1). The potential chemopreventive effects of Curc against redox stress have been strengthened by the observation that free and unmetabolized Curc is detectable inside the cells after 5 min of treatment, and its presence parallels with increased levels of intracellular Glutathione (GSH). These findings suggest that supplementation with Curc in the form of nutraceuticals may represent a promising way to protect people living in highly polluted areas against the adverse effects of HM contaminants.