Vitamin D₃ attenuates cisplatin-induced intestinal injury by inhibiting ferroptosis, oxidative stress, and ROS-mediated excessive mitochondrial fission.

Intestinal injury is one of the main side-effects of cisplatin (CP) chemotherapy, severely limiting the clinical application of CP. Vitamin D₃ is an essential nutrient for mammals and exists in a wide range of foods; it regulates immune function and reduces oxidative stress. However, the effect of vitamin D₃ on CP-induced intestinal injury is not elucidated. This is the first study to investigate the relationship between ferroptosis and the protective effect of vitamin D₃ on CP-induced intestinal injury. An animal model of CP-induced intestinal injury was established to evaluate the effect of vitamin D₃ on CP-induced intestinal injury and elucidate the underlying mechanisms. We found that vitamin D₃ alleviated intestinal barrier injury and the abnormal morphological structure in CP-induced intestinal injury mice. Vitamin D₃ suppressed oxidative stress by increasing the antioxidant capacity, inhibiting the accumulation of ROS and MDA, and reducing intestinal inflammatory responses....