| Registro completo |
| Provedor de dados: |
BJMBR
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| País: |
Brazil
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| Título: |
Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice
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| Autores: |
Araújo,C.V.
Lazzarotto,C.R.
Aquino,C.C.
Figueiredo,I.L.
Costa,T.B.
de Oliveira Alves,L.A.
Ribeiro,R.A.
Bertolini,L.R.
Lima,A.A.M.
Brito,G.A.C.
Oriá,R.B.
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| Data: |
2015-06-01
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| Ano: |
2015
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| Palavras-chave: |
Apolipoprotein E
5-Fluorouracil
Alanyl-glutamine
Mucositis
Mice
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| Resumo: |
Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE-/-) and wild-type (APOE+/+) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE-/--challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge.
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| Tipo: |
Info:eu-repo/semantics/article
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| Idioma: |
Inglês
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| Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2015000600493
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| Editor: |
Associação Brasileira de Divulgação Científica
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| Relação: |
10.1590/1414-431x20144360
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| Formato: |
text/html
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| Fonte: |
Brazilian Journal of Medical and Biological Research v.48 n.6 2015
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| Direitos: |
info:eu-repo/semantics/openAccess
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