Synergistic synbiotic containing fructooligosaccharides and Lactobacillus delbrueckii CIDCA 133 alleviates chemotherapy-induced intestinal mucositis in mice.

Intestinal mucositis is a commonly reported side effect in oncology patients undergoing chemotherapy and radiotherapy. Probiotics, prebiotics, and synbiotics have been investigated as alternative therapeutic approaches against intestinal mucositis due to their well-known anti-inflammatory properties and health benefits to the host. Previous studies showed that the potential probiotic Lactobacillus delbrueckii CIDCA 133 and the prebiotic Fructooligosaccharides (FOS) alleviated the 5-Fluorouracil (5-FU) chemotherapy-induced intestinal mucosa damage. Based on these previous beneficial effects, this work evaluated the anti-inflammatory property of the synbiotic formulation containing L. delbrueckii CIDCA 133 and FOS in mice intestinal mucosa inflammation induced by 5-FU. This work showed that the synbiotic formulation was able to modulate inflammatory parameters, including reduction of cellular inflammatory infiltration, gene expression downregulation of Tlr2, Nfkb1, and Tnf, and upregulation of the immunoregulatory Il10 cytokine, thus protecting the intestinal mucosa from epithelial damage caused by the 5-FU. The synbiotic also improved the epithelial barrier function by upregulating mRNA transcript levels of the short chain fatty acid (SCFA)-associated GPR43 receptor and the occludin tight junction protein, with the subsequent reduction of paracellular intestinal permeability. The data obtained showed that this synbiotic formulation could be a promising adjuvant treatment to be explored against inflammatory damage caused by 5-FU chemotherapy.

Polysaccharide Fraction from Campomanesia adamantium and Campomanesia pubescens Attenuates 5-Fluorouracil-Induced Intestinal Mucosal Inflammation in Mice.

Gastrointestinal toxicity, including diarrhea and inflammation, is commonly observed with the use of 5-fluorouracil (5-FU). Several studies have shown that polysaccharides are interesting bioactive macromolecules for the treatment or prevention of gastrointestinal diseases. Therefore, in this study, the effect of a polysaccharide fraction from a mixture of two Guavira species (Campomanesia adamantium and Campomanesia pubescens), referred to here as CPW, on the development of intestinal mucositis was investigated. Intestinal mucositis was induced by a single injection of 5-FU (450 mg/kg), and various doses of CPW (3-100 mg/kg) were tested. CPW attenuated disease development and prevented small bowel dysmotility and colon shortening. CPW prevented the increase in villi width, crypt depth, and mucosal thickness in the duodenum, but not in the colon. Preservation of mucus, reduction of oxidative stress, inflammation, and prevention of the 5-FU-induced enlargement and swelling of the spleen were observed. In conclusion, this study demonstrated for the first time that CPW alleviates the intestinal damage induced by 5-FU and could be used as an adjuvant strategy during chemotherapy.

Developing Ice Cream for Mucositis Management and Improving the Nutritional Support for Pediatric Cancer Patients / Desenvolvimento de um Sorvete para Prevenção e Tratamento da Mucosite e Suporte Nutricional a Pacientes Pediátricos com Câncer / Desarrollo de Helados para el Manejo de la Mucositis y del Soporte Nutricional a Pacientes Pediátricos con Cáncer

Introduction: Mucositis is one of the main complications of cancer treatment, associated with several nutritional limitations and the ability to cause secondary infections. Cryotherapy is a low-cost treatment consistent with clinical practice guidelines for treating patients with mucositis. Objective: To develop and evaluate the acceptance of ice cream for the prevention and treatment of mucositis and nutritional support of pediatric cancer patients. Method: Based on knowledge about the side effects of chemotherapy (especially in oral and gastrointestinal mucositis) and the nutritional needs of pediatric cancer patients, a literature search for ingredients that could meet the study's objectives was undertaken. Food Technology Laboratory of the São Paulo State University (Unesp), Botucatu campus, and in partnership with Sorvetes Naturais ice cream shop in the municipality of Botucatu-SP, produced the ice cream. An acceptance test was applied in ten patients undergoing cancer treatment and 30 individuals in the control group using the 5-point mixed facial hedonic scale. Results: The final formula consisted of semi-skimmed lactose-free milk, extra virgin coconut oil, oat flour, honey, chamomile, Fortini food supplement, demerara sugar, and stabilizer/emulsifier. 90% of patients undergoing cancer treatment rated the final product as "liked" or "loved it," compared to 63% of the control group. Conclusion: Development of an ice cream that met the objectives of the study was possible through the choice of its composition. Honey and chamomile can favor the prevention of mucositis, and other ingredients offer the caloric density and protein supply.

Introdução: A mucosite é uma das principais complicações do tratamento oncológico, está associada a várias limitações nutricionais e é capaz de causar infecções secundárias. A crioterapia é uma forma de tratamento de baixo custo, consistente com as diretrizes de prática clínica para o cuidado de pacientes com mucosite. Objetivo: Desenvolver e avaliar a aceitação de um sorvete para prevenção e tratamento da mucosite e para suporte nutricional de pacientes pediátricos com câncer. Método: Baseado no conhecimento sobre os efeitos colaterais da quimioterapia (especialmente na mucosite oral e gastrointestinal) e nas necessidades nutricionais do paciente oncológico pediátrico, buscou-se, na literatura, por ingredientes que pudessem alcançar os objetivos do estudo. O sorvete foi produzido no Laboratório de Tecnologia de Alimentos da Universidade Estadual Paulista (Unesp), campus de Botucatu, e em parceria com a sorveteria Sorvetes Naturais no município de Botucatu-SP. Foi realizado teste de aceitação com dez pacientes em tratamento oncológico e com 30 indivíduos do grupo controle usando a escala hedônica facial mista de 5 pontos. Resultados: A fórmula final consistiu em leite sem lactose semidesnatado, óleo de coco extravirgem, farinha de aveia, mel, camomila, suplemento alimentar Fortini, açúcar demerara e estabilizante/emulsificante. Dos pacientes em tratamento oncológico, 90% classificaram o produto final em "gostei" ou "adorei", comparado com 63% do grupo controle. Conclusão: O desenvolvimento de um sorvete que alcançasse os objetivos do estudo foi possível por meio da escolha da sua composição. O mel e a camomila podem favorecer a prevenção da mucosite, e outros ingredientes oferecem densidade calórica e oferta proteica.

Introducción: La mucositis es una de las principales complicaciones del tratamiento del cáncer, asociada a varias limitaciones nutricionales y la capacidad de causar infecciones secundarias. La crioterapia es una forma de tratamiento de bajo costo consistente con las guías de práctica clínica para el cuidado de pacientes con mucositis. Objetivo: Desarrollar y evaluar la aceptación de un helado para la prevención y tratamiento de la mucositis y para el apoyo nutricional de pacientes pediátricos con cáncer. Método: Con base en el conocimiento sobre los efectos secundarios de la quimioterapia (especialmente en la mucositis oral y gastrointestinal) y las necesidades nutricionales de los pacientes con cáncer pediátrico, buscamos en la literatura ingredientes que pudieran lograr los objetivos del estudio. El helado fue producido en el Laboratorio de Tecnología de Alimentos de la Universidad Estatal de São Paulo (Unesp), campus de Botucatu y en sociedad con la heladería Sorvetes Naturais del municipio de Botucatu-SP. Se realizó una prueba de aceptación con diez pacientes en tratamiento oncológico y 30 individuos del grupo control utilizando la escala hedónica facial mixta de 5 puntos. Resultados: La fórmula final estuvo compuesta por leche semidesnatada sin lactosa, aceite de coco virgen extra, harina de avena, miel, manzanilla, complemento alimenticio Fortini, azúcar demerara y estabilizante/emulsionante. El 90% de los pacientes en tratamiento contra el cáncer calificaron el producto final como "me gustó" o "me encantó", en comparación con el 63% del grupo de control. Conclusión: El desarrollo de un helado que cumpliera con los objetivos del estudio fue posible a través de la elección de su composición. La miel y la manzanilla pueden favorecer la prevención de la mucositis y otros ingredientes ofrecen densidad calórica y aporte proteico.

Kappaphycus Alvarezii Compound Powder Prevents Chemotherapy-Induced Intestinal Mucositis in BALB/c Mice.

This study aimed to formulate Kappaphycus alvarezii compound powder containing Kappaphycus alvarezii powder (KP), cooked sorghum powder (SP), and longan powder (LP); which was evaluated for its therapeutic effects against chemotherapy-induced intestinal mucosal injury (CIMI). Based on rheological properties, sensory evaluation, and antioxidant activity and using single factor and response surface methodology, the optimal formula to develop the compound powder was determined to be 35% KP, 30% SP, 5% LP, and 30% xylitol. Thereafter, the efficacy of the compound powder was tested by feeding BALB/c mice with diets supplemented with the Kappaphycus alvarezii compound powder (3% and 5%) for 14 consecutive days. The chemotherapeutic drug 5-fluorouracil was intraperitoneally injected (50 mg/kg) in the mice to induce CIMI for the last three consecutive days. Compared to the CIMI mice, those fed 5% Kappaphycus alvarezii compound powder (HC) showed significantly improved the intestinal injury, increased mucin-2 secretion, and reduced TNF-α, IL-1ß, IL-6, LT, and COX-2 levels. Furthermore, HC intake significantly reduced the Firmicutes-to-Bacteroidetes ratio, promoted the growth of beneficial bacteria, such as Alloprevotella, and inhibited the growth of harmful bacteria, such as Clostridium. In conclusion, HC has a protective effect against CIMI and provides a novel dietary strategy for patients undergoing chemotherapy.

Investigation of the protective effect of gel incorporating Eugenia jambolana leaf extract on 5-fluorouracil-induced oral mucositis: an animal study.

PURPOSE: The study aimed to evaluate the possible preventive effect of two concentrations (3 and 5% w/w) of Eugenia jambolana (EJ) extract against 5-FU-induced mucositis. METHOD: Sixteen adult rats were separated into four groups: two control and two preventive groups. Animals in Groups 1, 2, and 3 were injected intraperitoneally with 60 mg/kg/day of 5-FU on Day 1 followed by 150 mg/kg/day on Day 5. The rats in Group 4 (negative control) were given physiological saline at the same times and doses. Furthermore, on the fifth day of the study, the cheek and sublingual mucosa were irritated by external superficial scratches using the tip of an 18-G needle, followed by the application 15 µL of 20% acetic acid, after which 3 and 5% EJ w/w gels were applied topically for animals in Groups 2 and 3, respectively. RESULTS: The weight and the mucositis scores were recorded. Antioxidant and anti-inflammatory markers and biochemical tests were analyzed. Significant differences were found between the study groups in weight loss, clinical mucositis scores, mortality rates, and antioxidant and anti-inflammatory parameters. CONCLUSION: The preventive effect of 3% gel was significant, with no mortality rate, making it an option for preventive strategies.

Efficacy of Kanglaite against radiotherapy-induced mucositis in head and neck cancer, a phase II trial.

PURPOSE: To explore the potential protective effect of Kanglaite injection against radiotherapy-induced mucositis in patients with head and neck cancer. PATIENTS AND METHODS: This was an open-label, single-arm, and phase II trial. The primary endpoint was the incidence of grade 3-4 radiation-induced mucositis. The secondary endpoints were hematological toxicity, non-hematological toxicity, nutritional status, and quality of life. All patients received 20g Kanglaite daily concurrently with radiotherapy. RESULTS: The data of 46 patients were available for analysis. The incidence rates of grade 3 mucositis, pain, dysphagia, and neutropenia were 10.9%, 2.2%, 10.9%, and 6.5%, respectively, while the incidence of grade 4 acute toxicities was zero. The rate of opioid use was 2.2%. Radiotherapy dose reduction was 2.2% and no irradiation field was modified. The nutritional supports were oro-enteral nutritional supplements (13.0%), TPN (10.9%), and feeding tubes (0%) during radiotherapy. After radiotherapy, 52.2% of patients lost weight, and the weight loss was <10%. The mean pain score in the QLQ-H&N35 and QLQ-C30 was <50. Patients had nearly normal physical, emotional, and cognitive functions. CONCLUSIONS: A low incidence of grade 3-4 radiation-induced mucositis and no severe acute toxic events, with favorable nutritional status and quality of life, were observed in cancer patients after Kanglaite injection. Our findings highlight the need for a prospective, multicenter, and randomized study to investigate the effect of Kanglaite injection on the reduction of radiation-induced mucositis in patients with head and neck cancer.

Sun-Dried and Air-Dried Kappaphycus alvarezii Attenuates 5-Fluorouracil-Induced Intestinal Mucositis in Mice.

5-fluorouracil (5-FU)-induced intestinal mucositis (IM) often makes chemotherapy patients suffer from physical and psychological suffering. Kappaphycus alvarezii (KA) is known for its potent multiple biological activities from decades. In the current study, we explored the effect of sun-dried and air-dried Kappaphycus alvarezii as a whole food supplement on 5-FU-induced IM. Diets supplemented with sun-dried Kappaphycus alvarezii (SKA, 3%), air-dried Kappaphycus alvarezii (AKA, 3%), and 5-aminosalicylic acid (0.005%) for consecutive14 days. While intraperitoneal injection of 5-FU (50 mg/kg) induced IM for last three consecutive days, and IM was assessed by the disease activity index (DAI) and inflammatory cytokine levels. Pretreatment of KA could alleviate phenotypic index, inhibit the increase of DAI, and reverse villus/crypt ratio. On the 14th day, AKA significantly increased the weight growth rate of the mice. The intervention of SKA significantly reduced the level of TNF-α and IL-1ß (P < 0.01, P < 0.01), while the intervention of AKA significantly inhibited the level of TNF-α, IL-1ß, and LT (P < 0.01, P < 0.01, P < 0.001). Therefore, these results showed that KA as a whole food supplement might be prevent the 5-FU-induced IM. For the first time suggest that the use of AKA might be more effective than SKA despite exact mechanism still needs further study.

Antarctic Strain of Rhodotorula mucilaginosa UFMGCB 18,377 Attenuates Mucositis Induced by 5-Fluorouracil in Mice.

Mucositis is one of the most strenuous side effects caused by chemotherapy drugs, such as 5-fluorouracil (5-FU), during the treatment of several types of cancers. The disease is so prevalent and aggressive that many patients cannot resist such symptoms. However, despite its frequency and clinical significance, there is no effective treatment to prevent or treat mucositis. Thus, the use of probiotics as an adjuvant for the treatment has gained prominence. In the present study, we evaluated the effectiveness of oral administration of the Antarctic strain of Rhodotorula mucilaginosa UFMGCB 18,377 as an alternative to minimize side effects of 5-FU-induced mucositis in mice. Body weight, food consumption, stool consistency, and presence of blood in the feces were assessed daily in mice orally treated or not with the yeast and submitted or not to experimental mucositis. Blood, bones, and intestinal tissues and fluid were used to determine intestinal permeability and immunological, microbiological, and histopathological parameters. Treatment with R. mucilaginosa UFMGCB 18,377 was able to decrease clinical signs of the disease, such as reduction of food intake and body weight loss, and also decreased the number of intestinal enterobacteria and intestinal length shortening. Additionally, treatment was able to decrease the levels of MPO and EPO activities and inflammatory infiltrates, as well as the histopathological lesions characteristic of mucositis in the jejunum and ileum. Results of the present study showed that the oral administration of R. mucilaginosa UFMGCB 18,377 protected mice against mucositis induced by 5-FU.

Development of a self-limiting model of methotrexate-induced mucositis reinforces butyrate as a potential therapy.

Gastrointestinal mucositis is a complication of anticancer treatment, with few validated in vitro systems suitable to study the complex mechanisms of mucosal injury. Therefore, we aimed to develop and characterize a chemotherapeutic-induced model of mucositis using 3D intestinal organoids. Organoids derived from mouse ileum were grown for 7 days and incubated with different concentrations of the chemotherapeutic agent methotrexate (MTX). Metabolic activity, citrulline levels and cytokine/chemokine production were measured to determine the optimal dosage and incubation time. The protective effects of folinic acid on the toxicity of MTX were investigated by pre-treating organoids with (0.0005-50 µg/mL) folinic acid. The impact of microbial-derived short-chain fatty acids was evaluated by supplementation with butyrate in the organoid model. MTX caused a dose-dependent reduction in cell metabolic activity and citrulline production that was salvaged by folinic acid treatment. Overall, MTX causes significant organoid damage, which can be reversed upon removal of MTX. The protective effect of folinic acid suggest that the organoids respond in a clinical relevant manner. By using the model for intervention, it was found that prophylactic treatment with butyrate might be a valuable strategy for prophylactic mucositis prevention.

Role of honey in preventing radiation-induced oral mucositis: a meta-analysis of randomized controlled trials.

BACKGROUND: Radiotherapy-induced mucositis easily arouses oral ulceration, pain and xerostomia. Intense pain, difficulty swallowing and speaking greatly affect the quality of life and the treatment process. OBJECTIVE: This study aimed to examine the effects of honey in preventing and treating radiotherapy-induced mucositis in patients with head and neck cancer using a different analytical strategy. METHODS: Articles published until July 2020 were searched across PubMed, Embase, and Cochrane Library databases. Randomized controlled trials that evaluated honey were assessed by two reviewers. The number of mucositis incidences was the primary outcome. Weight loss, pain scale and incidence of severe pain were pooled to be calculated as secondary outcomes. Statistical analyses were conducted using RevMan5.3 software. The funnel plot was used to detect publication bias. RESULTS: Overall, 11/179 records with 715 patients who received radiotherapy were included. Honey significantly reduced the incidence of grade 2 (OR: 0.43, 95%CI: 0.54-0.98, P = 0.03), grade 3 (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.16-0.35, P < 0.001) and grade 4 mucositis (OR: 0.17, 95%CI: 0.08-0.36, P < 0.001). In grade 1 (OR: 1.54, 95%CI: 1.15-2.06, P = 0.003), and honey was not significant in preventing radiation-induced mucositis. The incidence of unbearable pain was lower in the honey group at all grades (OR: -0.20, 95%CI: -0.33 to -0.07). The effect of honey on weight loss and pain score was not statistically significant. CONCLUSION: Honey can prevent and alleviate grade 2-4 mucositis, especially in high grade mucositis. Honey also provides some relief from severe pain. But, more evidence is required to prove that honey is an effective substance for relieving pain or minimizing weight loss.

Anti-inflammatory effects of Radix Aucklandiae herbal preparation ameliorate intestinal mucositis induced by 5-fluorouracil in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: 5-Fluorouracil (5-FU) is a chemotherapy agent that is widely used in clinical oncologic practice. However, intestinal mucositis is the most frequently occurring side effect of cancer therapy with 5-FU. Based on a literature survey, Radix Aucklandiae herbal preparation potentially ameliorates intestinal mucositis in 5-FU-treated mice. AIM OF THE STUDY: The aim of this study was to investigate the inflammation and gastrointestinal regulation of intestinal mucositis induced by 5-FU, including the intestinal morphology, as well as the reduction in food intake, body weight loss, and diarrhea. MATERIALS AND METHODS: Intestinal mucositis was induced in mice by 5-FU (30 mg/kg, i.p., for 5 consecutive days). The dose-dependent Radix Aucklandiae herbal preparation (0.3, 1, and 3 g/kg/day, p.o.), loperamide (3 mg/kg/day, p.o.) or celecoxib (40 mg/kg/day, p.o.) was concurrently administered until the 7th day. Physical status observation, diarrhea assessment, serum proinflammatory cytokine levels, intestinal villus height and crypt depth, and total goblet cells from tissues were assessed. RESULTS: The dosage regimen of 5-FU administration caused severe intestinal mucositis in mice, including damage to the intestinal morphology, accompanied by a reduction in food intake, body weight loss, and diarrhea. The high-dose Radix Aucklandiae herbal preparation significantly relieves 5-FU-induced intestinal mucositis by enhancing proliferative activity in epithelial crypts; improving anepithymia, body weight loss, and diarrhea; and displaying protective effects on goblet cells in intestinal mucosal epithelia. Activation of NF-κB in the intestinal mucositis model was also suppressed by the Radix Aucklandiae herbal preparation, suggesting that it is a potent inhibitor of NF-κB and proinflammatory cytokines, such as IL-1ß, IL-6, TNF-α, and COX-2. CONCLUSIONS: Our data support the conclusion that the Radix Aucklandiae herbal preparation could effectively ameliorate 5-FU-induced gastrointestinal toxicity and be applied clinically for the prevention of intestinal mucositis during chemotherapy.

Glutamine for Amelioration of Radiation and Chemotherapy Associated Mucositis during Cancer Therapy.

Glutamine is a major dietary amino acid that is both a fuel and nitrogen donor for healing tissues damaged by chemotherapy and radiation. Evidence supports the benefit of oral (enteral) glutamine to reduce symptoms and improve and/or maintain quality of life of cancer patients. Benefits include not only better nutrition, but also decreased mucosal damage (mucositis, stomatitis, pharyngitis, esophagitis, and enteritis). Glutamine supplementation in a high protein diet (10 grams/day) + disaccharides, such as sucrose and/or trehalose, is a combination that increases glutamine uptake by mucosal cells. This increased topical effect can reduce painful mucosal symptoms and ulceration associated with chemotherapy and radiation in the head and neck region, esophagus, stomach and small intestine. Topical and oral glutamine seem to be the preferred routes for this amino acid to promote mucosal healing during and after cancer treatment.

Patchouli alcohol attenuates 5-fluorouracil-induced intestinal mucositis via TLR2/MyD88/NF-kB pathway and regulation of microbiota.

Intestinal mucositis causes great suffering to cancer patients who undergo chemotherapy and radiotherapy. Owing to the uncertain side effects of anticancer drugs to attenuate patients' intestinal mucositis, many studies focused on traditional Chinese medicine (TCM). Patchouli alcohol (PA) is an active compound extracted from Pogostemon cablin, and has potent gastrointestinal protective effect. However, whether PA has an effect on intestinal mucositis is still unknown. Therefore, we established a rat model of intestinal mucositis via intraperitoneal injection of 5-fluorouracil, and intragastrically administrated PA (10, 20, and 40 mg/kg) to evaluate the effect of PA on intestinal mucositis. The routine observation (body weight, food intake, and diarrhea) in rats was used to detect whether PA had an effect on intestinal mucositis. Levels of inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-10, and MPO), mucosal barrier proteins (zonula occludens -1 (ZO-1), claudin-1, occludin, myosin light chain (MLC), and mucin-2) and intestinal microbiota were determined to elucidate the underlying mechanism of PA action on intestinal mucositis in rats. The results showed that PA could effectively improve body weight, food intake, and diarrhea in intestinal mucositis rats, preliminary confirming PA efficacy. Further experiments revealed that PA not only decreased the levels of TNF-α, IL-1ß, IL-6, and MPO but also increased the level of IL-10 significantly. In addition, the expression of mucosal barrier proteins and microbiota community were also improved after PA treatment in diseased rats. Hence, PA may prevent the development and progression of intestinal mucositis by improving inflammation, protecting mucosal barrier, and regulating intestinal microbiota.

Patchouli oil ameliorates 5-fluorouracil-induced intestinal mucositis in rats via protecting intestinal barrier and regulating water transport.

ETHNOPHARMACOLOGICAL RELEVANCE: Pogostemon cablin, commonly named "Guang-Huo-Xiang" in China, has long been renowned for its ability to dispel dampness and regulate gastrointestinal functions. Patchouli oil (P.oil), the major active fraction of Pogostemon cablin, has been traditionally used as the principal component of Chinese medicinal formulae to treat exterior syndrome and diarrhea. However, the effects of P.oil in treating 5-fluorouracil (5-FU)-induced intestinal mucositis have not yet been reported. AIM OF THE STUDY: To investigate the protective effects of P.oil against 5-FU-induced intestinal mucositis and the mechanisms underlying these effects. MATERIALS AND METHODS: Sprague-Dawley rats were intraperitoneally injected with 5-FU (30 mg/kg) to establish an intestinal mucositis model. Meanwhile, rats with intestinal mucositis were orally administered with P.oil (25, 50, and 100 mg/kg). Histological analysis, ELISA (for detecting inflammatory cytokines and aquaporins), immunohistochemistry analysis (for examining caspases), qRT-PCR analysis (for assessment tight junctions), and western blotting analysis (for the assessment of TLR2/TLR4-MyD88 and VIP-cAMP-PKA signaling pathway-related proteins) were performed to estimate the protective effects of P.oil against intestinal mucositis and the mechanisms underlying these effects. RESULTS: The histopathological assessment preliminarily exhibited that P.oil alleviated the 5-FU-induced damage to the intestinal structure. After P.oil administration, the elevation of the expression of cytokines (TNF-α, IFN-γ, and IL-13) decreased markedly and the activation of NF-κB and MAPK signaling was significantly inhibited. P.oil also increased the mRNA expression of ZO-1 and Occludin, thereby stabilizing intestinal barrier. In addition, P.oil decreased the expressions of caspase-8, caspase-3, and Bax, and increased the expression of Bcl-2, thereby reducing the apoptosis of the intestinal mucosa. These results were closely related to the regulation of the TLR2/TLR4-MyD88 signaling pathway. It has been indicated that P.oil possibly protected the intestinal barrier by reducing inflammation and apoptosis. Furthermore, this study showed that P.oil inhibited the abnormal expression of AQP3, AQP7, and AQP11 by regulating the VIP-cAMP-PKA signaling pathway. Furthermore, it restored the intestinal water absorption, thereby alleviating diarrhea. CONCLUSIONS: P.oil ameliorated 5-FU-induced intestinal mucositis in rats via protecting intestinal barrier and regulating water transport.

Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines-part 1: vitamins, minerals, and nutritional supplements.

PURPOSE: To update the clinical practice guidelines for the use of natural and miscellaneous agents for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, out of which 29 were included in this part, and were analyzed with 27 previously reviewed studies. A new Suggestion was made for oral glutamine for the prevention of OM in head and neck (H&N) cancer patients receiving radiotherapy with concomitant chemotherapy. The previous Recommendation against the use of parenteral glutamine for the prevention of OM in hematopoietic stem cell transplantation (HSCT) patients was re-established. A previous Suggestion for zinc to prevent OM in H&N cancer patients treated with radiotherapy or chemo-radiotherapy was reversed to No Guideline Possible. No guideline was possible for other interventions. CONCLUSIONS: Of the vitamins, minerals, and nutritional supplements studied for the management of OM, the evidence supports a Recommendation against parenteral glutamine in HSCT patients and a Suggestion in favor of oral glutamine in H&N cancer patients for the management of OM.

Systematic review of agents for the management of cancer treatment-related gastrointestinal mucositis and clinical practice guidelines.

PURPOSE: The aim of this study was to update the clinical practice guidelines for the use of agents for the prevention and/or treatment of gastrointestinal mucositis (GIM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, and No Guideline Possible. RESULTS: A total of 78 papers across 13 interventions were examined of which 25 were included in the final review. No new guidelines were possible for any agent due to inadequate and/or conflicting evidence. Existing guidelines for probiotics and hyperbaric oxygen were unchanged. CONCLUSIONS: Of the agents studied for the prevention and treatment of GIM, the evidence continues to support use of probiotics containing Lactobacillus spp. for prevention of chemoradiotherapy and radiotherapy-induced diarrhea in patients with pelvic malignancy, and hyperbaric oxygen therapy to treat radiation-induced proctitis. Additional well-designed research is encouraged to enable a decision regarding palifermin, glutamine, sodium butyrate, and dietary interventions, for the prevention or treatment of GIM.

Treatment with selenium-enriched Saccharomyces cerevisiae UFMG A-905 partially ameliorates mucositis induced by 5-fluorouracil in mice.

PURPOSE: Gastrointestinal mucositis is a major problem associated with cancer therapy. To minimize these deleterious effects, simultaneous administration of antioxidant components, such as selenium, can be considered. There is a growing interest in the use of yeasts because they are able to convert inorganic selenium into selenomethionine. In the present study, oral administration of Saccharomyces cerevisiae UFMG A-905 enriched with selenium was evaluated as an alternative in minimizing the side effects of 5FU-induced mucositis in mice. METHODS: Mice body weight, food consumption, faeces consistency and the presence of blood in faeces were assessed daily during experimental mucositis induced by 5-fluorouracil (5FU). Blood was used for intestinal permeability determination, and small intestine for oxidative stress, immunological and histopathological examination. RESULTS: The increased intestinal permeability observed with mucositis induction was partially reverted by S. cerevisiae and selenium-enriched yeast. Both treatments were able to reduce myeloperoxidase activity, but only selenium-enriched yeast reduced eosinophil peroxidase activity. CXCL1/KC levels, histopathological tissue damage and oxidative stress (lipid peroxidation and nitrite production) in the small intestine were reduced by both treatments; however, this reduction was always higher when treatment with selenium-enriched yeast was evaluated. CONCLUSIONS: Results of the present study showed that the oral administration of S. cerevisiae UFMG A-905 protected mice against mucositis induced by 5-FU, and that this effect was potentiated when the yeast was enriched with selenium.

Preventative effects of selenium-enriched Bifidobacterium longum on irinotecan-induced small intestinal mucositis in mice.

Intestinal mucositis is a frequent side effect in cancer patients who are treated with chemotherapy. There are no effective treatment strategies to date. To find a novel way to alleviate mucositis, the effects of selenium-enriched Bifidobacterium longum (Se-B. longum) in preventing irinotecan (CPT-11)-induced intestinal mucositis in a mouse model were investigated. We tested the ability of Se-B. longum (Se 0.6 mg/kg, 5×108 cfu/mice) to reduce small intestinal mucositis induced by CPT-11 (75 mg/kg, daily) injected intraperitoneally for four consecutive days in mice. Se-B. longum significantly decreased mortality induced by CPT-11 from 71.4% to 16.7%. CPT-11 induced body weight loss, which was alleviated by preventative and simultaneous administration of Se-B. longum. Se-B. longum significantly decreased the severity of diarrhoea from 11 to 4% compared to the CPT-11 group. Inflammation, including intestinal shortening and upregulation of tumour necrosis factor-α and interleukin-1ß induced by CPT- 11, were prevented by Se-B. longum. Se-B. longum is effective in preventing small intestinal mucositis induced by CPT-11 and therefore has potential to be used clinically by cancer patients.