Dietary CA supplementation decreases AOM/DSS-induced colitis in Nrf2+/+ but not Nrf2−/− mice. A, Eight-week-old Nrf2+/+ and Nrf2−/− mice were fed with standard diet or received diet supplemented with 0.5% CA. AOM injection was performed at the beginning of week 9, followed by three cycles of DSS (2.5 %) administration in drinking water. CA-supplementation was initiated one week before AOM injection and then maintained after AOM injection for one (CA2) or ten (CA11) weeks. Eleven weeks after the initiation of the experiment, mice were sacrificed for analysis. B, CA supplementation significantly decreased loss of crypts and maintained mucosal crypt organization in Nrf2+/+ mice only, as demonstrated by H&E staining (100 x magnification). C, Histopathological assessment of colon mucosa in Nrf2+/+ and Nrf2−/− mice was performed following the chronic colitis scoring system described in Materials and Methods. Horizontal lines indicate median values (*p<0.05; Mann-Whitney test); N.S.: not significant. D, AOM/DSS-induced weight loss was significantly attenuated by CA11 supplementation in Nrf2+/+ mice. The graph indicates average body weight (mean + SD) per treatment group at the beginning and at the end of the experimental regimen (eleven weeks total duration; *p < 0.05 versus control; #p < 0.05 versus AOM/DSS;). E–F, AOM/DSS-induced body weight loss in Nrf2+/+ versus Nrf2−/− mice was analyzed as a function of CA supplementation. At the end of the treatment regimen, the relative weight loss was compared between treatment groups; the difference between AOM/DSS versus untreated control was numerically defined as 1 (*p < 0.05).