Skip to main content
Erschienen in: Supportive Care in Cancer 4/2016

01.04.2016 | Original Article

Influence of an elemental diet on 5-fluorouracil-induced morphological changes in the mouse salivary gland and colon

verfasst von: Rei Kawashima, Mio Fujimaki, Yuka Ikenoue, Keiko Danjo, Wasaburo Koizumi, Takafumi Ichikawa

Erschienen in: Supportive Care in Cancer | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The elemental diet (ED) Elental® reportedly reduces adverse reactions to chemotherapy in digestive system cancer patients; however, the mechanism is unclear. Therefore, we verified the protective effect of ED against gastrointestinal disorders induced by the antineoplastic drug 5-fluorouracil (5-FU).

Methods

After 5 days of tail vein injections of 40 mg/kg/day 5-FU in female BALB/c mice, the mice were given oral ED (ED group) or dextrin with the same number of calories (control group). We measured the weight of salivary glands and the PAS-positive area of colonic mucosa and verified the antitumor effect in tumor-bearing mice given 5-FU and ED.

Results

Although body weight decreased after 5-FU treatment, ED group mice weighed more than control group mice. Additionally, although control mice developed diarrhea after 5-FU treatment, the ED group showed only loose stools. The control group saliva volume was approximately one sixth of the vehicle group volume after 5-FU treatment; this was improved to approximately half in the ED group. The area ratio of PAS-positive cells in the colonic mucosa was reduced by 5-FU treatment, with the ratio being higher in the ED group than that in the control group. Similar tumor growth suppression was observed in the 5-FU and ED groups.

Conclusions

ED alleviated adverse reactions to 5-FU without affecting antitumor activity. Protection against 5-FU-induced weight loss was potentially due to both improved nutritional support with combined ingredients and prevention of diarrhea that is associated with reduced colonic goblet cells and decreased saliva production from reduced salivary gland contraction.
Literatur
1.
Zurück zum Zitat Elting LS, Cooksley C, Chambers M, et al. (2003) The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer 98:1531–1539CrossRefPubMed Elting LS, Cooksley C, Chambers M, et al. (2003) The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer 98:1531–1539CrossRefPubMed
2.
Zurück zum Zitat Slavin RE, Dias MA, Saral R (1978) Cytosine arabinoside induced gastrointestinal toxic alterations in sequential chemotherapeutic protocols: a clinical-pathologic study of 33 patients. Cancer 42:1747–1759CrossRefPubMed Slavin RE, Dias MA, Saral R (1978) Cytosine arabinoside induced gastrointestinal toxic alterations in sequential chemotherapeutic protocols: a clinical-pathologic study of 33 patients. Cancer 42:1747–1759CrossRefPubMed
3.
Zurück zum Zitat Lochs H, Dejong C, Hammarqvist F, et al. (2006) ESPEN guidelines on enteral nutrition: gastroenterology. Clin Nutr 25:260–274CrossRefPubMed Lochs H, Dejong C, Hammarqvist F, et al. (2006) ESPEN guidelines on enteral nutrition: gastroenterology. Clin Nutr 25:260–274CrossRefPubMed
4.
Zurück zum Zitat Homan M, Baldassano RN, Mamula P (2005) Managing complicated Crohn’s disease in children and adolescents. Nat Clin Pract Gastroenterol Hepatol 2:572–579CrossRefPubMed Homan M, Baldassano RN, Mamula P (2005) Managing complicated Crohn’s disease in children and adolescents. Nat Clin Pract Gastroenterol Hepatol 2:572–579CrossRefPubMed
5.
Zurück zum Zitat Johnson T, Macdonald S, Hill SM, et al. (2006) Treatment of active Crohn’s disease in children using partial enteral nutrition with liquid formula: a randomised controlled trial. Gut 55:356–361PubMedCentralCrossRefPubMed Johnson T, Macdonald S, Hill SM, et al. (2006) Treatment of active Crohn’s disease in children using partial enteral nutrition with liquid formula: a randomised controlled trial. Gut 55:356–361PubMedCentralCrossRefPubMed
6.
Zurück zum Zitat Yamamoto T, Nakahigashi M, Umegae S, et al. (2005) Impact of elemental diet on mucosal inflammation in patients with active Crohn’s disease: cytokine production and endoscopic and histological findings. Inflamm Bowel Dis 11:580–588CrossRefPubMed Yamamoto T, Nakahigashi M, Umegae S, et al. (2005) Impact of elemental diet on mucosal inflammation in patients with active Crohn’s disease: cytokine production and endoscopic and histological findings. Inflamm Bowel Dis 11:580–588CrossRefPubMed
7.
Zurück zum Zitat Kawaguchi T, Mori M, Saito K, et al. (2015) Food antigen-induced immune responses in Crohn’s disease patients and experimental colitis mice. J. Gastroenterol Kawaguchi T, Mori M, Saito K, et al. (2015) Food antigen-induced immune responses in Crohn’s disease patients and experimental colitis mice. J. Gastroenterol
8.
Zurück zum Zitat Kajiura T, Takeda T, Sakata S, et al. (2009) Change of intestinal microbiota with elemental diet and its impact on therapeutic effects in a murine model of chronic colitis. Dig Dis Sci 54:1892–1900CrossRefPubMed Kajiura T, Takeda T, Sakata S, et al. (2009) Change of intestinal microbiota with elemental diet and its impact on therapeutic effects in a murine model of chronic colitis. Dig Dis Sci 54:1892–1900CrossRefPubMed
9.
Zurück zum Zitat Andou A, Hisamatsu T, Okamoto S, et al. (2009) Dietary histidine ameliorates murine colitis by inhibition of proinflammatory cytokine production from macrophages. Gastroenterology 136:564–774 e2CrossRefPubMed Andou A, Hisamatsu T, Okamoto S, et al. (2009) Dietary histidine ameliorates murine colitis by inhibition of proinflammatory cytokine production from macrophages. Gastroenterology 136:564–774 e2CrossRefPubMed
10.
Zurück zum Zitat Ogata Y, Takeuchi M, Ishibashi N, et al. (2012) Efficacy of Elental on prevention for chemotherapy-induced oral mucositis in colorectal cancer patients. Gan To Kagaku Ryoho. 39:583–587PubMed Ogata Y, Takeuchi M, Ishibashi N, et al. (2012) Efficacy of Elental on prevention for chemotherapy-induced oral mucositis in colorectal cancer patients. Gan To Kagaku Ryoho. 39:583–587PubMed
11.
Zurück zum Zitat Fukui T, Itoh Y, Orihara M, et al. (2011) Elental prevented and reduced oral mucositis during chemotherapy in patients esophageal cancer. Gan To Kagaku Ryoho 38:2597–2601PubMed Fukui T, Itoh Y, Orihara M, et al. (2011) Elental prevented and reduced oral mucositis during chemotherapy in patients esophageal cancer. Gan To Kagaku Ryoho 38:2597–2601PubMed
12.
Zurück zum Zitat Azuumi Y, Ohara S, Ishihara K, et al. (1980) Correlation of quantitative changes of gastric mucosal glycoproteins with aspirin-induced gastric damage in rats. 21:533–536. Azuumi Y, Ohara S, Ishihara K, et al. (1980) Correlation of quantitative changes of gastric mucosal glycoproteins with aspirin-induced gastric damage in rats. 21:533–536.
13.
Zurück zum Zitat Ikezawa T, Ichikawa T, Adachi K, et al. (2005) Analysis of mucin composition in gastric juices of chronic rheumatic patients with upper gastrointestinal damage. Biomed Res 26:147–151CrossRefPubMed Ikezawa T, Ichikawa T, Adachi K, et al. (2005) Analysis of mucin composition in gastric juices of chronic rheumatic patients with upper gastrointestinal damage. Biomed Res 26:147–151CrossRefPubMed
14.
Zurück zum Zitat Kojima Y, Ishihara K, Ohara S, et al. (1992) Effects of the M1 muscarinic receptor antagonist pirenzepine on gastric mucus glycoprotein in rats with or without ethanol-induced gastric damage. Scand J Gastroenterol 27:764–768CrossRefPubMed Kojima Y, Ishihara K, Ohara S, et al. (1992) Effects of the M1 muscarinic receptor antagonist pirenzepine on gastric mucus glycoprotein in rats with or without ethanol-induced gastric damage. Scand J Gastroenterol 27:764–768CrossRefPubMed
15.
Zurück zum Zitat Ikezawa T, Goso Y, Ichikawa T, et al. (2002) Immunohistochemical localization in rat gastrointestinal tract of a sialomucin species recognized by HCM31, a new anti-mucin monoclonal antibody. Biochem Res. 23:63–68 Ikezawa T, Goso Y, Ichikawa T, et al. (2002) Immunohistochemical localization in rat gastrointestinal tract of a sialomucin species recognized by HCM31, a new anti-mucin monoclonal antibody. Biochem Res. 23:63–68
16.
Zurück zum Zitat Ishihara K, Kurihara M, Goso Y, et al. (1996) Establishment of monoclonal antibodies against carbohydrate moiety of gastric mucins distributed in the different sites and layers of rat gastric mucosa. Glycoconj J 13:857–864CrossRefPubMed Ishihara K, Kurihara M, Goso Y, et al. (1996) Establishment of monoclonal antibodies against carbohydrate moiety of gastric mucins distributed in the different sites and layers of rat gastric mucosa. Glycoconj J 13:857–864CrossRefPubMed
17.
Zurück zum Zitat Tsubokawa D, Goso Y, Sawaguchi A, et al. (2007) A monoclonal antibody, PGM34, against 6-sulfated blood-group H type 2 antigen, on the carbohydrate moiety of mucin. FEBS J. 274:1833–1848CrossRefPubMed Tsubokawa D, Goso Y, Sawaguchi A, et al. (2007) A monoclonal antibody, PGM34, against 6-sulfated blood-group H type 2 antigen, on the carbohydrate moiety of mucin. FEBS J. 274:1833–1848CrossRefPubMed
18.
Zurück zum Zitat Saegusa Y, Ichikawa T, Iwai T, et al. (2008) Effects of acid antisecretory drugs on mucus barrier of the rat against 5-fluorouracil-induced gastrointestinal mucositis. Scand J Gastroenterol 43:531–537PubMedCentralCrossRefPubMed Saegusa Y, Ichikawa T, Iwai T, et al. (2008) Effects of acid antisecretory drugs on mucus barrier of the rat against 5-fluorouracil-induced gastrointestinal mucositis. Scand J Gastroenterol 43:531–537PubMedCentralCrossRefPubMed
19.
Zurück zum Zitat Yamamoto H, Ishihara K, Takeda Y, et al. (2013) Changes in the mucus barrier during cisplatin-induced intestinal mucositis in rats. Biomed Res Int. doi:10.1155/2013/276186 Yamamoto H, Ishihara K, Takeda Y, et al. (2013) Changes in the mucus barrier during cisplatin-induced intestinal mucositis in rats. Biomed Res Int. doi:10.​1155/​2013/​276186
20.
Zurück zum Zitat Imamura TK, Yoshino Y, Yamachika S, et al. (2012) Inhibition of pilocarpine-induced saliva secretion by adrenergic agonists in ICR mice. Clin Exp Pharmacol Physiol. 39:1038–1043CrossRefPubMed Imamura TK, Yoshino Y, Yamachika S, et al. (2012) Inhibition of pilocarpine-induced saliva secretion by adrenergic agonists in ICR mice. Clin Exp Pharmacol Physiol. 39:1038–1043CrossRefPubMed
21.
Zurück zum Zitat Saegusa Y, Ichikawa T, Iwai T, et al. (2008) Changes in the mucus barrier of the rat during 5-fluorouracil-induced gastrointestinal mucositis. Scand J Gastroenterol 43:59–65CrossRefPubMed Saegusa Y, Ichikawa T, Iwai T, et al. (2008) Changes in the mucus barrier of the rat during 5-fluorouracil-induced gastrointestinal mucositis. Scand J Gastroenterol 43:59–65CrossRefPubMed
22.
Zurück zum Zitat Jensen SB, Pedersen AM, Reibel J, et al. (2003) Xerostomia and hypofunction of the salivary glands in cancer therapy. Support Care Cancer 11:207–225PubMed Jensen SB, Pedersen AM, Reibel J, et al. (2003) Xerostomia and hypofunction of the salivary glands in cancer therapy. Support Care Cancer 11:207–225PubMed
23.
Zurück zum Zitat McCarthy GM, Awde JD, Ghandi H, et al. (1998) Risk factors associated with mucositis in cancer patients receiving 5-fluorouracil. Oral Oncol 34:484–490CrossRefPubMed McCarthy GM, Awde JD, Ghandi H, et al. (1998) Risk factors associated with mucositis in cancer patients receiving 5-fluorouracil. Oral Oncol 34:484–490CrossRefPubMed
24.
Zurück zum Zitat Harrison T, Bigler L, Tucci M, et al. (1998) Salivary sIgA concentrations and stimulated whole saliva flow rates among women undergoing chemotherapy for breast cancer: an exploratory study. Spec Care Dentist 18:109–112CrossRefPubMed Harrison T, Bigler L, Tucci M, et al. (1998) Salivary sIgA concentrations and stimulated whole saliva flow rates among women undergoing chemotherapy for breast cancer: an exploratory study. Spec Care Dentist 18:109–112CrossRefPubMed
25.
Zurück zum Zitat Dumbrigue HB, Sandow PL, Nguyen KH, et al. (2000) Salivary epidermal growth factor levels decrease in patients receiving radiation therapy to the head and neck. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 89:710–716CrossRefPubMed Dumbrigue HB, Sandow PL, Nguyen KH, et al. (2000) Salivary epidermal growth factor levels decrease in patients receiving radiation therapy to the head and neck. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 89:710–716CrossRefPubMed
26.
Zurück zum Zitat Iwai T, Ichikawa T, Goso Y, et al. (2009) Effects of indomethacin on the rat small intestinal mucosa: immunohistochemical and biochemical studies using anti-mucin monoclonal antibodies. J Gastroenterol 44:277–284CrossRefPubMed Iwai T, Ichikawa T, Goso Y, et al. (2009) Effects of indomethacin on the rat small intestinal mucosa: immunohistochemical and biochemical studies using anti-mucin monoclonal antibodies. J Gastroenterol 44:277–284CrossRefPubMed
Metadaten
Titel
Influence of an elemental diet on 5-fluorouracil-induced morphological changes in the mouse salivary gland and colon
verfasst von
Rei Kawashima
Mio Fujimaki
Yuka Ikenoue
Keiko Danjo
Wasaburo Koizumi
Takafumi Ichikawa
Publikationsdatum
01.04.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Supportive Care in Cancer / Ausgabe 4/2016
Print ISSN: 0941-4355
Elektronische ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-015-2947-7

Weitere Artikel der Ausgabe 4/2016

Supportive Care in Cancer 4/2016 Zur Ausgabe

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

16.05.2024 alpha-1-Rezeptorantagonisten Nachrichten

Nach einer Prostatabiopsie treten häufig Probleme beim Wasserlassen auf. Ob sich das durch den periinterventionellen Einsatz von Alphablockern verhindern lässt, haben australische Mediziner im Zuge einer Metaanalyse untersucht.

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

15.05.2024 Mammakarzinom Nachrichten

Frauen mit lokalem oder metastasiertem Brustkrebs, die Statine einnehmen, haben eine niedrigere krebsspezifische Mortalität als Patientinnen, die dies nicht tun, legen neue Daten aus den USA nahe.

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

13.05.2024 Pankreaskarzinom Nachrichten

Gerade bei aggressiven Malignomen wie dem duktalen Adenokarzinom des Pankreas könnte Früherkennung die Therapiechancen verbessern. Noch jedoch klafft hier eine Lücke. Ein Studienteam hat einen Weg gesucht, sie zu schließen.

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

12.05.2024 Prostatakarzinom Nachrichten

Ein hoher Anteil pflanzlicher Nahrung trägt möglicherweise dazu bei, das Progressionsrisiko von Männern mit Prostatakarzinomen zu senken. In einer US-Studie war das Risiko bei ausgeprägter pflanzlicher Ernährung in etwa halbiert.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.