FIGURE 4.

A systematic schematic of protective agents against drug-induced toxicity via modulating the mutual interference between Nrf2 and NF-κB pathways. The protective candidates improve the antioxidant capacity by activating the Nrf2 pathway and inhibiting the NF-κB-mediated inflammatory response, thereby antagonizing the drug-induced organ toxicity. Specifically, on the one hand, the protective agents directly or indirectly activate the Nrf2 signaling, then prevent IκBα degradation, or increase HO-1 expression to inhibit NF-κB activation, thereby increasing antioxidant defense ability to resist drug-induced toxicity. On the other hand, the protective agents may inhibit the nuclear translocation of NF-κB which activating by drug-induced toxicity to increase the activation of the Nrf2 pathway by increasing ARE gene transcription and Free CBP, and reducing the recruitment of HDAC3 to the ARE region.