Hence, natural agents or compounds with antioxidant/anti-inflammatory properties, or those that help mitigate redox signaling and associated inflammation, may be suitable candidates to restrain 5-FU-enhanced kidney damage via the Nrf2/Keap1 and p38-MAPK/NF-κB pathways, thus providing striking therapeutic signaling targets for drug discovery. This evidence concerns the gene NFE2L2 and Nephropathy.