Skip to main content

01.12.2014 | SHORT REPORT | Ausgabe 6/2014

Investigational New Drugs 6/2014

Human uridine phosphorylase-1 inhibitors: a new approach to ameliorate 5-fluorouracil-induced intestinal mucositis

Investigational New Drugs > Ausgabe 6/2014
Daiana Renck, André A. Santos Jr, Pablo Machado, Guilherme O. Petersen, Tiago G. Lopes, Diógenes S. Santos, Maria M. Campos, Luiz A. Basso
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s10637-014-0135-0) contains supplementary material, which is available to authorized users.


Purpose 5-fluorouracil (5-FU) has been broadly used to treat solid tumors for more than 50 years. One of the major side effects of fluoropyrimidines therapy is oral and intestinal mucositis. Human uridine phosphorylase (hUP) inhibitors have been suggested as modulators of 5-FU toxicity. Therefore, the present study aimed to test the ability of hUP blockers in preventing mucositis induced by 5-FU. Methods We induced intestinal mucositis in Wistar rats with 5-FU, and the intestinal damage was evaluated in presence or absence of two hUP1 inhibitors previously characterized. We examined the loss of weight and diarrhea following the treatment, the villus integrity, uridine levels in plasma, and the neutrophil migration by MPO activity. Results We found that one of the compounds, 6-hydroxy-4-methyl-1H-pyridin-2-one-3-carbonitrile was efficient to promote intestinal mucosa protection and to inhibit the hUP1 enzyme, increasing the uridine levels in the plasma of animals. However, the loss of body weight, diarrhea intensity or neutrophil migration remained unaffected. Conclusion Our results bring support to the hUP1 inhibitor strategy as a novel possibility of prevention and treatment of mucositis during the 5-FU chemotherapy, based on the approach of uridine accumulation in plasma and tissues.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

Online Resource 1 (DOC 53 kb)
Über diesen Artikel

Weitere Artikel der Ausgabe 6/2014

Investigational New Drugs 6/2014 Zur Ausgabe

Neu im Fachgebiet Onkologie

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Onkologie und bleiben Sie gut informiert – ganz bequem per eMail.