Glutamine and alanyl-glutamine accelerate the recovery from 5-fluorouracil-induced experimental oral mucositis in hamster

Leitão, Renata F. C.; Ribeiro, Ronaldo A.; Lira, A. M. S.; Silva, L. R.; Bellaguarda, E. A. L.; Macedo, Filipa; Sousa, Romualdo Barroso de; Brito, Gerly A. C.

doi:10.1007/s00280-007-0463-2

Cited by 38 publications

(23 citation statements)

References 34 publications

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“…These observations were consistent with the peak of the inflammatory process described in the literature 12,13,15,16 . It was observed that macroscopically, when the cys-LT blocker dose was increased to 40 mg/ kg/d for 10 d, partial protection against OM induced by 5-FU occurred, but not as intense as when COX-2 was blocked.…”

Section: ■ Discussionsupporting

confidence: 81%

Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil

Silva

Leitão²,

Brito³

et al. 2017

Acta Cir. Bras.

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Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil 1 AbstractPurpose: To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. Methods: Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/ kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. Results: Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1β between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)-α expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. Conclusions: Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.

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Section: ■ Discussionsupporting

confidence: 81%

Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil

Silva

Leitão²,

Brito³

et al. 2017

Acta Cir. Bras.

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“…Interestingly, there is no evidence of off‐target effects of L‐citrulline in attenuating the chemotherapeutic action of 5FU, supporting its safe use during cancer treatment. In fact, previous studies have used the same model of mucositis associating with other compounds, indicating that no direct effects on the chemotherapeutic effect of 5FU are expected 23 , 24 , 28 . To our knowledge, this is the first study that has described the role of L‐citrulline in gut barrier function in this model.…”

Section: Discussionmentioning

confidence: 80%

Pretreatment With L‐Citrulline Positively Affects the Mucosal Architecture and Permeability of the Small Intestine in a Murine Mucositis Model

Antunes

Leocádio

Teixeira

et al. 2015

J Parenter Enteral Nutr

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“…There sections were analyzed by light microscopy. The criteria analyzed were included infiltration of inflammatory cells, vasodilatation, presence of hemorrhagic areas, edema, ulcerations, and abscesses were independently scored following the following classification: 1 – normal epithelium and connective tissue without vasodilation, absence or discrete cellular infiltration or absence of hemorrhagic areas, ulcerations or abscesses; 2 – discrete areas of vasodilation or re-epithelialization, mild inflammatory infiltration with mononuclear prevalence and absence of hemorrhagic areas, edema, ulcerations, or abscesses; 3 – moderate vasodilatation, areas of epithelial degeneration, inflammatory infiltration with neutrophil prevalence, presence of hemorrhagic areas, edema and eventual ulceration, and absence of abscesses; 4 – severe vasodilation and inflammatory infiltration with neutrophils (Leitao et al, 2007, 2008; Watanabe et al, 2009; Medeiros et al, 2011; Skeff et al, 2014; de Araujo et al, 2015; Ribeiro et al, 2017). …”

Section: Methodsmentioning

confidence: 99%

Telmisartan Modulates the Oral Mucositis Induced by 5-Fluorouracil in Hamsters

et al. 2018

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Oral mucositis (OM) is a common adverse effect resulting from cancer therapy. The OM it has implications that may compromise oncologic treatment and decrease the patient’s quality of life. The therapeutic options to prevent or treat the symptoms of OM are scarce; there is no effective therapy that improves the symptoms. Based on the need for further research for the treatment of OM, the present study objective was to evaluate the effect of telmisartan (TELM) on the OM induced by 5-fluorouracil (5-FU), using as animal model Golden Syrian hamsters. 5-FU followed by mechanical trauma on day 4 was used to induce OM in hamsters. Euthanasia occurred on the day 10. The experiments were constituted by the groups saline, mechanical trauma, 5-FU, and TELM in three doses (1, 5, or 10 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The samples also were used for analysis enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reactions (qPCR). TELM (5 or 10 mg/kg) was able to reduce the inflammatory ulceration and infiltration in the oral mucosa of the animals, decreasing the levels of the cytokines TNF-α and IL-1β. These treatments was minimize the immunostaining for cyclooxygenase-2, matrix metalloproteinase-9, transforming growth factor-β, and smad 2/3. The nuclear transcription factor kappa B (NFκB) p65 and inducible nitric oxide synthase were reduced in the oral mucosa. Finally, TELM (10 mg/kg) increased the PPARγ gene expression and reduced STAT1 and NFκB p65 gene expression relative to the 5-FU group. Therefore, TELM prevents the OM produced by 5-FU on animal model.

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Glutamine and alanyl-glutamine accelerate the recovery from 5-fluorouracil-induced experimental oral mucositis in hamster

Abstract: Glutamine or alanyl-glutamine accelerated the mucosal recovery increasing mucosal tissue glutathione stores, reducing inflammatory parameters and speeding reepithelization.

Cited by 38 publications

References 34 publications

Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil

Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil

Pretreatment With L‐Citrulline Positively Affects the Mucosal Architecture and Permeability of the Small Intestine in a Murine Mucositis Model

Telmisartan Modulates the Oral Mucositis Induced by 5-Fluorouracil in Hamsters

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