Phytochemicals Possess Selective Chemopreventive Mechanisms That Safeguard Human Cells from Oxidative Toxicity

Oxidative stress from environmental pollutants is linked to chronic degenerative diseases. Research indicates that specific phytochemicals in our diets can reduce and mitigate the harmful effects of pro-oxidant insults on health. However, limited randomized clinical trials show the protective effects of these compounds. This lack of in vivo evidence is partly due to the low bioavailability of these compounds, which can obscure their actual benefits. The present work investigates whether selected dietary phytochemicals are equally effective in activating cellular defense against oxidative stress at low doses. In a previous study, we found that Curcumin (Curc) at a concentration of 1 μM protected human myeloid cells from cytotoxicity induced by pro-oxidant species by activating the expression of Nrf2/ARE-dependent transcripts, including NADPH: quinone oxidoreductase-1 (NQO-1) and heme oxygenase-1 (HO-1). Now, we aim to extend our observation to other natural activators of the Nrf2 pathway, such as Sulforaphane (SFN) and three structurally related molecules belonging to the flavonoid family: Quercetin (Q), Catechin (C), and Fisetin (F). These compounds were applied at low concentrations (1 μM) to assess their antioxidant activity against H₂O₂-induced oxidative stress, their effects on cellular viability, and the capacity to drive the expression of NQO-1/HO-1 in various cellular models. Our findings indicate that low-dose phytochemicals differ in their cytoprotective efficacy, which depends on both dosage and intracellular uptake or metabolism. We propose that only specific natural antioxidants can protect cells from oxidative stress, underscoring the need to clarify the mechanisms behind this selectivity to better design nutraceuticals and functional foods.