The role of toxic metals and metalloids in nrf2 signaling

Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2), an emerging regulator of cellular resis-tance to oxidants, serves as one of the key defensive factors against a range of pathological processessuch as oxidative damage, carcinogenesis, as well as various harmful chemicals, including metals.An increase in human exposure to toxic metals via air, food, and water has been recently observed,which is mainly due to anthropogenic activities. The relationship between environmental exposureto heavy metals, particularly cadmium (Cd), lead (Pb), mercury (Hg), and nickel (Ni), as well asmetaloid arsenic (As), and transition metal chromium (Cr), and the development of various humandiseases has been extensively investigated. Their ability to induce reactive oxygen species (ROS)production through direct and indirect actions and cause oxidative stress has been documentedin various organs. Taking into account that Nrf2 signaling represents an important pathway inmaintaining antioxidant balance, recent research indicates that it can play a dual role depending onthe specific biological context. On one side, Nrf2 represents a potential crucial protective mechanismin metal-induced toxicity, but on the other hand, it can also be a trigger of metal-induced carcinogen-esis under conditions of prolonged exposure and continuous activation. Thus, this review aims tosummarize the state-of-the-art knowledge regarding the functional interrelation between the toxicmetals and Nrf2 signaling.