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

Harada,Koji; Takenawa,Takanori; Ferdous,Tarannum; Mizukami,Yoichi; Mishima,Katsuaki

doi:10.3892/mco.2020.2050

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

Authors:
- Koji Harada
- Takanori Takenawa
- Tarannum Ferdous
- Yoichi Mizukami
- Katsuaki Mishima
View Affiliations

Affiliations: Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan, Center for Gene Research, Yamaguchi University, Ube, Yamaguchi 755‑8505, Japan
Published online on: May 22, 2020 https://doi.org/10.3892/mco.2020.2050
Pages: 209-215

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Online EA Pharma Co., Ltd Products Information, Elental®. http://www.eapharma.co.jp/medicalexpert/product/elental/elentalinformation.html, Webpage in Japanese. Accessed online: 25 July 2019.
2	Kawada J, Nishino M, Hata T, Tanizaki K, Ogino T, Hoshino H, Okano M, Nagai K, Kim Y, Okuyama M, et al: Analysis of patients who received nutritional support and the enhanced recovery after surgery (ERAS) protocol after esophagectomy. Gan To Kagaku Ryoho. 45:1524–1526. 2018.(In Japanese). PubMed/NCBI
3	Ohkura Y, Haruta S, Tanaka T, Ueno M and Udagawa H: Effectiveness of postoperative elemental diet (Elental^®) in elderly patients after gastrectomy. World J Surg Oncol. 14(268)2016.PubMed/NCBI View Article : Google Scholar
4	Imamura H, Nishikawa K, Kishi K, Inoue K, Matsuyama J, Akamaru Y, Kimura Y, Tamura S, Kawabata R, Kawada J, et al: Effects of an oral elemental nutritional supplement on post-gastrectomy body weight loss in gastric cancer patients: A randomized controlled clinical trial. Ann Surg Oncol. 23:2928–2935. 2016.PubMed/NCBI View Article : Google Scholar
5	Yamamoto T, Nakahigashi M, Umegae S, Kitagawa T and Matsumoto K: Impact of elemental diet on mucosal inflammation in patients with active Crohn's disease: Cytokine production and endoscopic and histological findings. Inflamm Bowel Dis. 11:580–588. 2005.PubMed/NCBI View Article : Google Scholar
6	Hanai H, Iida T, Takeuchi K, Arai H, Arai O, Abe J, Tanaka T, Maruyama Y, Ikeya K, Sugimoto K, et al: Nutritional therapy versus 6-mercaptopurine as maintenance therapy in patients with Crohn's disease. Dig Liver Dis. 44:649–54. 2012.PubMed/NCBI View Article : Google Scholar
7	Johtatsu T, Andoh A, Kurihara M, Iwakawa H, Tsujikawa T, Kashiwagi A, Fujiyama Y and Sasaki M: Serum concentrations of trace elements in patients with Crohn's disease receiving enteral nutrition. J Clin Biochem Nutr. 4:197–201. 2007.PubMed/NCBI View Article : Google Scholar
8	Yamamoto T, Nakahigashi M, Saniabadi AR, Iwata T, Maruyama Y, Umegae S and Matsumoto K: Impacts of long-term enteral nutrition on clinical and endoscopic disease activities and mucosal cytokines during remission in patients with Crohn's disease: A prospective study. Inflamm Bowel Dis. 13:1493–1501. 2007.PubMed/NCBI View Article : Google Scholar
9	Yamamoto T, Nakahigashi M, Umegae S, Kitagawa T and Matsumoto K: Impact of long-term enteral nutrition on clinical and endoscopic recurrence after resection for Crohn's disease: A prospective, non-randomized, parallel, controlled study. Aliment Pharmacol Ther. 25:67–72. 2007.PubMed/NCBI View Article : Google Scholar
10	Kawada J, Nishino M, Hata T, Ogino T, Hoshino H, Okano M, Nagai K, Kim Y, Okuyama M and Tsujinaka T: Analysis of patients who received enteral nutrition in the course of chemotherapy. Gan To Kagaku Ryoho. 44:900–902. 2017.(In Japanese). PubMed/NCBI
11	Kawaguchi Y, Lin JC, Kawashima Y, Maruno A, Ito H, Ogawa M and Mine T: Relationship between pain and plasma amino acid levels in chronic pancreatitis. JOP. 16:53–57. 2015.PubMed/NCBI View Article : Google Scholar
12	Ogata Y, Ishibashi N, Yamaguchi K, Uchida S, Kamei H, Nakayama G, Hirakawa H, Tanigawa M and Akagi Y: Preventive effects of amino-acid-rich elemental diet Elental® on chemotherapy-induced oral mucositis in patients with colorectal cancer: A prospective pilot study. Support Care Cancer. 24:783–789. 2016.PubMed/NCBI View Article : Google Scholar
13	Ogata Y, Takeuchi M, Ishibashi N, Kibe S, Takahashi K, Uchida S, Murakami N, Yahara T and Shirouzu K: Efficacy of Elental on prevention for chemotherapy-induced oral mucositis in colorectal cancer patients. Gan To Kagaku Ryoho. 39:583–587. 2012.(In Japanese). PubMed/NCBI
14	Toyomasu Y, Mochiki E, Yanai M, Suzuki M, Yanoma T, Kimura A, Kogure N, Ogata K and Kuwano H: A prospective pilot study of an elemental nutritional supplement for prevention of oral mucositisduring S-1 adjuvant chemotherapy for gastric cancer. Surg Oncol. 29:97–101. 2019.PubMed/NCBI View Article : Google Scholar
15	Ishikawa T, Yasuda T, Doi T, Okayama T, Sakamoto N, Gen Y, Dohi O, Yoshida N, Kamada K, Uchiyama K, et al: The amino acid-rich elemental diet Elental^® preserves lean body mass during chemo- or chemoradiotherapy for esophageal cancer. Oncol Rep. 36:1093–1100. 2016.PubMed/NCBI View Article : Google Scholar
16	Fukui T, Itoh Y, Orihara M, Yoshizawa K, Takeda H, Kawada S and Yoshioka T: Elental prevented and reduced oral mucositis during chemotherapy in patients esophageal cancer. Gan To Kagaku Ryoho. 38:2597–2601. 2011.(In Japanese). PubMed/NCBI
17	Miki H, Tokuhara K, Oishi M, Tanaka Y, Nakatake R, Ueyama Y, Kaibori M, Nishizawa M, Okumura T and Kon M: Elental^® amino acid component has protective effects on primary cultured hepatocytes and a rat model of acute liver injury. Nutr Res. 42:71–84. 2017.PubMed/NCBI View Article : Google Scholar
18	Harada K, Ferdous T, Horinaga D, Uchida K, Mano T, Mishima K, Park S, Hanazawa H, Takahashi S, Okita A, et al: Efficacy of elemental diet on prevention for chemoradiotherapy-induced oral mucositis in patients with oral squamous cell carcinoma. Support Care Cancer. 24:953–959. 2016.PubMed/NCBI View Article : Google Scholar
19	Harada K, Minami H, Ferdous T, Kato Y, Umeda H, Horinaga D, Uchida K, Park SC, Hanazawa H, Takahashi S, et al: The Elental^® elemental diet for chemoradiotherapy-induced oral mucositis: A prospective study in patients with oral squamous cell carcinoma. Mol Clin Oncol. 10:159–167. 2019.PubMed/NCBI View Article : Google Scholar
20	Harada K, Ferdous T, Kobayashi H and Ueyama Y: Elemental diet accelerates the recovery from oral mucositis and dermatitis induced by 5-Fluorouracil through the induction of fibroblast growth factor 2. Integr Cancer Ther. 17:423–430. 2018.PubMed/NCBI View Article : Google Scholar
21	Harada K, Ferdous T, Mizukami Y and Mishima K: Elemental diet inhibits pro-inflammatory cytokine production in keratinocytes through the suppression of NF-κB activation. Oncol Rep. 40:361–368. 2018.PubMed/NCBI View Article : Google Scholar
22	Svanberg A, Ohrn K and Birgegard G: Oral cryotherapy reduces mucositis and improves nutrition- A randomised controlled trial. J Clin Nurs. 19:2146–2151. 2010.PubMed/NCBI View Article : Google Scholar
23	Scully C, Epstein J and Sonis S: Oral mucositis: A challenging complication of radiotherapy, chemotherapy, and radiochemotherapy. Part 2: Diagnosis and management of mucositis. Head Neck. 26:77–84. 2004.PubMed/NCBI View Article : Google Scholar
24	Cowen D, Tardieu C, Schubert M, Peterson D, Resbeut M, Faucher C and Franquin JC: Low energy helium-neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: Results of a double blind randomized trial. Int J Radiat Oncol Biol Phys. 38:697–703. 1997.PubMed/NCBI View Article : Google Scholar
25	O´Dwyer ST, Scott T, Smith RJ and Wilmore DW: 5-fluorouracil toxicity on small intestinal mucosa but not white blood cells is decreased by glutamine. Clin Res. 35(367A)1987.
26	Carneiro-Filho BA, Oriá RB, Wood Rea K, Brito GA, Fujii J, Obrig T, Lima AA and Guerrant RL: Alanyl-glutamine hastens morphologic recovery from 5-fluorouracil-induced mucositis in mice. Nutrition. 20:934–941. 2004.PubMed/NCBI View Article : Google Scholar
27	Kandil HM, Argenzio RA, Chen W, Berschneider HM, Stiles AD, Westwick JK, Rippe RA, Brenner DA and Rhoads JM: L-glutamine and l-asparagine stimulate ODC activity and proliferation in a porcine jejunal enterocyte line. Am J Physiol. 269:G591–G599. 1995.PubMed/NCBI View Article : Google Scholar
28	Rhoads JM, Argenzio RA, Chen W, Rippe RA, Westwick JK, Cox AD, Berschneider HM and Brenner DA: L-glutamine stimulates intestinal cell proliferation and activates mitogen-activated protein kinases. Am J Physiol. 272:G943–G953. 1997.PubMed/NCBI View Article : Google Scholar
29	Hong RW, Rounds JD, Helton WS, Robinson MK and Wilmore DW: Glutamine preserves liver glutathione after lethal hepatic injury. Ann Surg. 215:114–119. 1992.PubMed/NCBI View Article : Google Scholar
30	Denno R, Rounds JD, Faris R, Holejko LB and Wilmore DW: Glutamine-enriched total parenteral nutrition enhances plasma glutathione in the resting state. J Surg Res. 61:35–38. 1996.PubMed/NCBI View Article : Google Scholar