The chemopreventive effects of Curcumin against oxidative stress induced by Cadmium or H2O2 are mediated by Nrf2/ARE signaling and protective 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 (Cur), a natural polyphenol, is particularly effective in protecting against Cadmium (Cd) toxicity. The present study demonstrates that preincubation with low doses of Cur (1 M) in differentiated HL-60 and K-562 human myeloid cells can significantly protect against cytotoxicity induced by Cd and or H2O2. Cur reduced the increased levels of reactive oxygen species (ROS) generated by Cd or H2O2 by inducing a protective form of autophagy. Cur activated mild oxidative stress that triggers the expression of Nrf2-dependent transcripts, such as HO and NQO1. The potential chemopreventive effects of Cur against redox stress have been strengthened by the observation that free and unmetabolized Cur is detectable inside the cells after 5 minutes of treatment, and its presence parallels with increased levels of intracellular GSH. These findings suggest that supplementation with Cur 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.