Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

Autor: C.V. Araújo, C.R. Lazzarotto, C.C. Aquino, I.L. Figueiredo, T.B. Costa, L.A. de Oliveira Alves, R.A. Ribeiro, L.R. Bertolini, A.A.M. Lima, G.A.C. Brito, R.B. Oriá
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Brazilian Journal of Medical and Biological Research, Vol 48, Iss 6, Pp 493-501 (2015)
Druh dokumentu: article
ISSN: 1414-431X
DOI: 10.1590/1414-431X20144360
Popis: 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
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