Background/Aim: This study aimed to identify the most useful components of Elental ® in the treatment of 5fluorouracil (FU)-induced mucositis and salivary gland atrophy in mice. Materials and Methods: Mice (except the control group) were intraperitoneally injected with 5-FU. The mice received saline (control group and 5-FU group), dextrin (Dextrin group), amino acids (17AA group), or Elental ® (Elental ® group). Results: The volume and weight of salivary glands was higher in 17AA and Elental ® groups compared to 5-FU group. The number of mucous glands was higher, whereas the number of damaged granular ductal epithelial cells was lower in the salivary glands of all groups except the 5-FU group. Salivation was also decreased in the 5-FU group compared to the other groups. Conclusion: Amino acids could be the most effective components of Elental ® for protecting mouse salivary glands from 5-FUinduced atrophic changes, and might be useful in the treatment of oral mucositis in cancer patients.

An elemental diet (ED) reduces adverse effects of chemotherapy, including oral mucositis, in patients with cancer. However, the detailed mechanism(s) of the healing effects of an ED remains unclear. In the present study, the protective effects of the ED, Elental ® , were examined against 5-fluorouracil (5-FU)-induced oral mucositis and salivary gland atrophy in mice. Mucositis was induced in female ICR mice by injection of 5-FU. The mice were orally administered Elental ® (ED group) or saline (control group). After treatment, the mice body weight, salivary gland weight and the histological changes in the salivary gland granular duct area were monitored. The mice body weight remained stable in the ED group, but was significantly decreased in the control group. Moreover, the salivary gland weight was higher in the ED group compared with the control group. In addition, the salivary gland granular duct area cells were larger in the ED group compared with the control group. Whole transcriptome analysis and network analysis were conducted to understand the mechanisms of action of Elental ® against oral mucositis. Whole transcriptome analysis and Ingenuity Pathways Analysis data suggested that Elental ® contributed to the recovery of mitochondrial function in 5-FU-damaged salivary glands. Immunohistochemical analysis of salivary gland tissue demonstrated that the expression of cytochrome c oxidase subunit 4 and epidermal growth factor were higher in the ED group compared with the control group. Next, the rate of apoptosis in the salivary glands was examined using terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assays. The number of TUNEL-positive cells in the salivary glands was lower in the ED group compared with the control group. These findings suggested that Elental ® may protect mouse salivary glands from 5-FU-induced atrophic changes, which suggests that ED treatment may improve xerostomia and alleviate oral mucositis in patients with cancer receiving 5-FU-based chemotherapy.