ArticleBrazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica2015
Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice.
Article in Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 34 citations in OpenAlex.
- Effects of different iron sources on growth performance, intestinal morphology, development, and cell proliferation in weanling piglets.Journal of nutritional science · 2025Article
- Polysaccharides from Passion Fruit Peels: From an Agroindustrial By-Product to a Viable Option for 5-FU-Induced Intestinal Damage.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Antarctic Strain of Rhodotorula mucilaginosa UFMGCB 18,377 Attenuates Mucositis Induced by 5-Fluorouracil in Mice.Probiotics and antimicrobial proteins · 2022Article
- Anti-inflammatory effect of L-cysteine (a semi-essential amino acid) on 5-FU-induced oral mucositis in hamsters.Amino acids · 2021Article
- Dietary Bioactive Peptide Alanyl-Glutamine Attenuates Dextran Sodium Sulfate-Induced Colitis by Modulating Gut Microbiota.Oxidative medicine and cellular longevity · 2021Article
- Beneficial Effects of Polysaccharides on the Epithelial Barrier Function in Intestinal Mucositis.Frontiers in physiology · 2021Review
- Acute blockade of endogenous melatonin by Luzindole, with or without peripheral LPS injection, induces jejunal inflammation and morphological alterations in Swiss mice.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2021Article
- Mining Anti-Inflammation Molecules FromFrontiers in cellular and infection microbiology · 2021Article
- Microbiota from alginate oligosaccharide-dosed mice successfully mitigated small intestinal mucositis.Microbiome · 2020Article
- Single-cell RNA sequencing analysis reveals alginate oligosaccharides preventing chemotherapy-induced mucositis.Mucosal immunology · 2020Review
- Volatile Oil from Amomi Fructus Attenuates 5-Fluorouracil-Induced Intestinal Mucositis.Frontiers in pharmacology · 2017Article
- Alteration of Gut Microbiota and Inflammatory Cytokine/Chemokine Profiles in 5-Fluorouracil Induced Intestinal Mucositis.Frontiers in cellular and infection microbiology · 2017Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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