Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in heavy metals-induced oxidative stress.

Organisms encounter reactive oxidants through intrinsic metabolism and environmental exposure to toxicants. Reactive oxygen and nitrogen species (ROS, RNS) are generally considered detrimental because they induce oxidative stress. In order to combat oxidative stress, a potential modulator of cellular defense nuclear factor erythroid 2-related factor 2 (Nrf2) and its endogenous inhibitor Kelch-like ECH-associated protein 1 (Keap1) operate as a common, genetically preserved intrinsic defense system. There has been a significant increase in the amount of harmful metalloids and metals that individuals are exposed to through their food, water, and air, primarily due to human activities. Many studies have looked at the connection between the emergence of different ailments in humans and ecological exposure to metalloids, i.e., arsenic (As) and metals viz., chromium (Cr), mercury (Hg), cadmium (Cd), cobalt (Co), and lead (Pb). It is known that they can produce ROS in several organs by both direct and indirect means. Studies suggest that Nrf2 signaling is a crucial mechanism in maintaining antioxidant balance and can have two roles, depending on the particular biological setting. From one perspective, Nrf2 is an essential defense mechanism against metal-induced toxicity. Still, it may also operate as a catalyst for metal-induced carcinogenesis in situations involving protracted exposure and persistent activation. Therefore, this review aims to provide an overview of the antioxidant defense mechanism of Nrf2-Keap1 signaling and the interrelation between Nrf2 signaling and the toxic elements.