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.