Inflammatory intestinal damage induced by 5-fluorouracil requires IL-4

Soares, Pedro Marcos Gomes; Mota, José Maurício; Souza, Emmanuel Prata de; Justino, Priscilla Fernanda Campos; Franco, Álvaro Xavier; Cunha, Fernando; Ribeiro, Ronaldo A.; Souza, Marcellus H.

doi:10.1016/j.cyto.2012.10.003

Cited by 68 publications

(64 citation statements)

References 14 publications

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“…Neutrophil infiltration has been reported in several studies that assessed mucositis (24,32,33). We observed intermediate MPO activity in animals receiving L-arginine.…”

Section: Discussionsupporting

confidence: 46%

L-Arginine Pretreatment Reduces Intestinal Mucositis as Induced by 5-FU in Mice

Leocádio

Antunes

Teixeira

et al. 2015

Nutrition and Cancer

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Beneficial effects of L-arginine on immune responses and bowel function have been reported. Mucositis is a side effect of chemotherapy treatment that affects approximately 40% of patients. This complication is characterized by inflammation that affects the gastrointestinal tract, increasing permeability and causing abdominal pain, nausea, vomiting, and diarrhea, which worsen the patient's nutritional status and increases morbimortality. The aim of this study was to evaluate the effect of pretreating with 2% L-arginine supplementation in water on mucositis as induced by 5-fluorouracil (5-FU; a single dose of 200 mg/kg body weight) in Swiss male mice. The effect of L-arginine on weight, intestinal permeability, morphology, and the histopathological score of the small intestine (from 0 to 12), oxidative stress, myeloperoxidase (MPO), and N-acetylglucosaminidase (NAG) activities were evaluated. Intestinal length improvement was observed, in addition to the partial recovery of the mucosal architecture. L-arginine attenuated the histopathological score and MPO activity. There was also an improvement in intestinal permeability, despite weight loss after 5-FU administration. In conclusion, L-arginine can positively impact intestinal mucositis by promoting partial mucosal recovery, reducing inflammation and improving intestinal permeability.

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“…Neutrophil infiltration has been reported in several studies that assessed mucositis (24,32,33). We observed intermediate MPO activity in animals receiving L-arginine.…”

Section: Discussionsupporting

confidence: 46%

L-Arginine Pretreatment Reduces Intestinal Mucositis as Induced by 5-FU in Mice

Leocádio

Antunes

Teixeira

et al. 2015

Nutrition and Cancer

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“…In addition, other factors, such as the use of some medications, can also contribute to the breakdown of this immunological tolerance against commensals. It has been reported that chemotherapeutic agents, such as 5-fluoracil, that are widely used in the treatment of advanced solid tumors, may also lead to the development of another inflammatory condition of the GIT known as mucositis, a disease characterized by painful inflammation and ulceration of the mucosal membranes (Soares et al, 2013; Pedroso et al, 2015). …”

Section: Introductionmentioning

confidence: 99%

Use of Wild Type or Recombinant Lactic Acid Bacteria as an Alternative Treatment for Gastrointestinal Inflammatory Diseases: A Focus on Inflammatory Bowel Diseases and Mucositis

et al. 2017

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The human gastrointestinal tract (GIT) is highly colonized by bacterial communities, which live in a symbiotic relationship with the host in normal conditions. It has been shown that a dysfunctional interaction between the intestinal microbiota and the host immune system, known as dysbiosis, is a very important factor responsible for the development of different inflammatory conditions of the GIT, such as the idiopathic inflammatory bowel diseases (IBD), a complex and multifactorial disorder of the GIT. Dysbiosis has also been implicated in the pathogenesis of other GIT inflammatory diseases such as mucositis usually caused as an adverse effect of chemotherapy. As both diseases have become a great clinical problem, many research groups have been focusing on developing new strategies for the treatment of IBD and mucositis. In this review, we show that lactic acid bacteria (LAB) have been capable in preventing and treating both disorders in animal models, suggesting they may be ready for clinical trials. In addition, we present the most current studies on the use of wild type or genetically engineered LAB strains designed to express anti-inflammatory proteins as a promising strategy in the treatment of IBD and mucositis.

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“…As observed in treated patients, 5-FU shows a high toxicity in gastrointestinal tract, inducing intestinal damage such as intestinal mucositis [34]. Previous studies have established the where R 1 is a C 1 -C 6 straight chain alkyl substituted with deuterium or (C 1 -C 5 straight chain alkylene)-COOR 2 wherein the straight chain alkylene is substituted with deuterium; and R 2 is selected from hydrogen, (C 1 -C 6 ) alkyl, (C 5 -C 14 ) aryl, (C 6 -C 16 ) arylalkyl, 5 --14 membered heteroaryl and 6 --16 membered heteroarylalkyl, wherein when R 2 is other than hydrogen, R 2 is optionally substituted with deuterium.…”

Section: -Fu Derivativesmentioning

confidence: 97%

5-Fluorouracil derivatives: a patent review (2012 – 2014)

Carrillo

Navarro-Marchal

Ramírez

et al. 2015

Expert Opinion on Therapeutic Patents

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Although in the past few years there has been a great advancement in the antitumor effectiveness and selectivity of 5-FU-based therapies, it is envisaged that future approaches using 'omics' technologies that could determine the tumor heterogeneity may help in identifying additional candidate genes, microRNAs or cytokines involved in both the path mechanisms of 5-FU-related toxicity and its therapeutic efficacy. Moreover, the development of novel targeted 5-FU derivatives or 5-FU-based therapies tailored to individual patients opens up new possibilities in the improvement of the quality of life and survival for those suffering from this devastating disease.

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Inflammatory intestinal damage induced by 5-fluorouracil requires IL-4

Abstract: Our data suggest that IL-4 participates as a pro-inflammatory cytokine in a 5-FU-induced intestinal damage model and suggests that IL-4 antagonists may be novel therapeutics for this condition.

Cited by 68 publications

References 14 publications

L-Arginine Pretreatment Reduces Intestinal Mucositis as Induced by 5-FU in Mice

L-Arginine Pretreatment Reduces Intestinal Mucositis as Induced by 5-FU in Mice

Use of Wild Type or Recombinant Lactic Acid Bacteria as an Alternative Treatment for Gastrointestinal Inflammatory Diseases: A Focus on Inflammatory Bowel Diseases and Mucositis

5-Fluorouracil derivatives: a patent review (2012 – 2014)

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