Role of Nrf2 in bisphenol effects: a review study
2022
Salehabadi, Amin | Farkhondeh, Tahereh | Harifi-Mood, Mohammad Sadra | Aschner, Michael | Samarghandian, Saeed
Bisphenols (BPs), the main endocrine-disrupting chemicals used in polycarbonate plastics, epoxy-phenol resins, and some other manufacturers, have been interestingly focused to find their toxic effects in recent years. Due to the strong relation between bisphenols and some crucial receptors such as ERs, AR, glucocorticoid receptor, THRs, ERRs, hPXR, AhR, and etcetera, the disrupting and oncogenic role of these chemicals on reproductive, respiratory, and circulatory systems and a broad group of body tissues have been investigated. BPs induce oxidant enzymes, exert antioxidant enzymes from body cells, and result in the expression of proinflammatory genes, leading to cell apoptosis and inflammation. To maintain the homeostasis of human body cells, Nrf2, the key regulator of oxidative stress (Ashrafizadeh et al., 2020a; Ashrafizadeh et al., 2020c; Boroumand et al., 2018), confronts BP-induced ROS and RNS through the activation of antioxidant enzymes such as SOD1/2, CAT, GSH, GPX, HO-1, and etcetera. Chemicals and drugs such as LUT, NAC, GEN, L-NMMA, Ph₂Se₂, and GE can regulate the interactions between BPs and Nrf2. Despite the vital role of controlled levels of Nrf2 as an anti-inflammatory and antiapoptotic element, the uncontrolled activity of this transcription factor could lead to cell proliferation and tumorigenesis through NQO1, SLC7a11, Gclm, HMOX1, NQO1 gene activation, and some other genes. To avoid the excessive activity of Nrf2, some protein complexes like CUL3-RBX1-Keap1 (as the primary regulator), β-TrCP, and WDR23 regulate Nrf2’s function. It is necessary to note that BPA, as the most famous member, is further reviewed due to its resemblance to the bisphenol family to each other.
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