Cr(VI) promotes tight joint and oxidative damage by activating the Nrf2/ROS/Notch1 axis.

This study aimed to investigate whether Cr(VI) induced tight joint and oxidative damage in the small intestine, as mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2)/reactive oxygen species (ROS)/Notch1 axis crosstalk. Thirty-two ICR mice were obtained and subjected to Cr(VI) via intragastric administration daily for 5 days. Western blot (WB) analysis, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) staining, and immunofluorescence (IF) staining were applied to detect small intestinal damage, Nrf2, Notch1, and respective downstream targets in this research. Results showed that Cr(VI) led to the tight joint and oxidative damage in the small intestine of mice. Nrf2 was stimulated, and Notch1 (Notch intracellular domain, NICD1) was activated to translocate into the nucleus and activate an antioxidant action. These findings were validated by WB analysis and IF staining. ROS levels increased as the Cr(VI) concentration increased. The colocalization analysis of Nrf2 and NICD1 implied that a crosstalk between Nrf2 and Notch1 existed. Therefore, this study indicated that the Nrf2/ROS/Notch1 axis crosstalk could aggravate the tight joint and oxidative damage in the small intestine after Cr(VI) treatment.