Adopting Nrf2 and NF-κB from cancer: Is there any role of the duo in diabetes?

Oxidative stress and inflammation are two well-recognized events occurring in normal cells during cancer chemotherapy. Several antioxidant and anti-inflammatory agents have therefore been tried as rational and effective strategies for chemoprotection. Elaborate studies on antioxidants and anti-inflammatory agents in various experimental models of cancer revealed that these agents act by modulating the expression and/or activity of transcription factors nuclear factor erythroid 2related factor 2 (Nrf2) and nuclear factor-kappa B (NFκB). Nrf2 is considered main sentinel of antioxidant defence as it induces many antioxidant and phase 2 enzymes in response to stressful conditions. Likewise NF-κB is considered as denominator of chronic and acute inflammatory processes. In the recent years, it was found that a large pool of chemopreventive and chemoprotective agents that restrain NF-κB inflammatory cascade also activates Nrf2 signaling. Diabetes and complications thereof are also conditions of amplified oxidative stress and inflammation in various targets organs like retina, kidneys, nerves and vasculature. Here we propose that Nrf2 and NF-κB are involved in the etiopathogenesis of diabetes and thus form attractive therapeutic targets. Elucidation of potential involvement of Nrf2 and NF-κB pathways that are operative during multi-organ injury in diabetes may provide basis for development of novel therapies.