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Erschienen in: Investigational New Drugs 6/2014

01.12.2014 | SHORT REPORT

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

verfasst von: Daiana Renck, André A. Santos Jr, Pablo Machado, Guilherme O. Petersen, Tiago G. Lopes, Diógenes S. Santos, Maria M. Campos, Luiz A. Basso

Erschienen in: Investigational New Drugs | Ausgabe 6/2014

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Summary

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.
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Metadaten
Titel
Human uridine phosphorylase-1 inhibitors: a new approach to ameliorate 5-fluorouracil-induced intestinal mucositis
verfasst von
Daiana Renck
André A. Santos Jr
Pablo Machado
Guilherme O. Petersen
Tiago G. Lopes
Diógenes S. Santos
Maria M. Campos
Luiz A. Basso
Publikationsdatum
01.12.2014
Verlag
Springer US
Erschienen in
Investigational New Drugs / Ausgabe 6/2014
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-014-0135-0

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