Elemental diet directly affects chemotherapy‑induced dermatitis and raw wound areas

Abstract

Elental ® is an L-glutamine-rich elemental diet (ED) that has been widely used in Japan as a nutritional supplement for malnourished patients. In addition, Elental ® has been successfully used in the management of chemotherapy-induced mucositis in cancer patients. Recently, it was also reported that Elental ® can effectively reduce chemotherapy-induced oral mucositis in patients with oral squamous cell carcinoma, and can also reduce mucositis and dermatitis in animal models. However, it is unclear whether oral intake or topical application of Elental ® can act directly on chemotherapy-induced oral mucositis or dermatitis. The aim of the present study was to investigate the possible direct healing effect of Elental ® on chemotherapy-induced dermatitis and raw wound areas in a mouse model. Dermatitis and raw wounds were induced in nude mice by administration of 5-fluorouracil (5-FU) (via gastric tube) and mechanical injury (using a metal brush or a surgical knife). We then compared the outcome following oral or topical application of Elental ® in these mice. The effect of Elental ® on the growth and migration ability of the human oral keratinocyte cell line, HOK, was also examined using MTT and migration assays, respectively. In the mouse model, both oral administration and topical application of Elental ® reduced 5-FU-induced dermatitis and healed raw wound areas more effectively compared with the topical application of saline. The MTT assay revealed that Elental ® exerted a growth-promoting effect on HOKs. In addition, Elental ® enhanced the ability of HOKs to migrate, as demonstrated by the migration assay. These findings demonstrated that the topical application as well as the oral intake of Elental ® exerted a direct healing effect on chemotherapy-induced dermatitis or raw wound areas. The data also indicated that oral intake of an ED may exert a direct healing effect on chemotherapy-induced oral mucositis.

Amino Acids May Have Protective Effects on Salivary Glands of 5-FU-administered Mice

“…We have been using Elental ® for treating malnutrition in patients undergoing chemotherapy in recent years. Moreover, we observed that Elental ® improved chemotherapy-induced oral mucositis (25)(26)(27)(28). Based on our previous data, we hypothesized that Elental ® or Elental ® components may protect salivary glands, preserve saliva secretion volume and alleviate oral mucositis by improving the oral environment.…”

“…Several clinical studies showed the beneficial effects of Elental ® against chemotherapy-induced mucositis in cancer patients (23,24). Animal studies have shown that ED with glutamine may protect the gut from chemotherapeutic agents and radiation, and can help in the treatment of chemotherapy-induced mucositis and dermatitis (7,9,25,26). We also reported the healing effects of Elental ® against chemotherapy-induced mucositis and dermatitis in head and neck cancer patients (27,28).…”

An elemental diet protects mouse salivary glands from 5‑fluorouracil‑induced atrophy

“…Over the past few years, the usefulness of EDs against the negative side effects of antineoplastic drugs has been observed in patients with cancer at Yamaguchi University Hospital. Elental ® was effective against chemotherapy-and/or radiotherapy-induced mucositis and dermatitis in HNC patients, as well as in vitro and in vivo (21,22,42,43). Based on these results, it was hypothesized that Elental ® may help to alleviate oral mucositis by preserving saliva secretion volume and improving the oral environment.…”

“…None of the patients complained of any irritation, pain or difficulty during oral administration (22). Moreover, murine back skin wounds are healed by topical application of Elental ® , which suggests that it may have direct soothing effects on the wounded areas upon contact (43). Therefore, it was assumed that Elental ® is suitable for patients with severe oral mucositis who are unable to eat solid foods.…”

Effectiveness of elemental diets to prevent oral mucositis associated with cancer therapy: A meta-analysis

“…In nude mice with 5-FU-induced dermatitis, oral ED decreased the expression of tumor necrosis factor-a, interleukin-1b, and interleukin-6, and decreased the transcriptional activation of NF-kB in keratinocytes, suggesting that ED may alleviate dermatitis and other inflammatory conditions induced by anticancer therapy [32]. ED also promoted the growth and migration of human oral keratinocytes, suggesting that it might minimize dermatitis and possibly oral mucositis by directly stimulating the development of these cells [33].…”