epiglucan and Mucositis

(1→3)-β-D-glucans (BG) (the glucose polymers) are recognized as pathogen motifs, and different forms of BGs are reported to have various effects. Here, different BGs, including Pachyman (BG with very few (1→6)-linkages), whole-glucan particles (BG with many (1→6)-glycosidic bonds), and Oat-BG (BG with (1→4)-linkages), were tested. In comparison with dextran sulfate solution (DSS) alone in mice, DSS with each of these BGs did not alter the weight loss, stool consistency, colon injury (histology and cytokines), endotoxemia, serum BG, and fecal microbiome but Pachyman-DSS-treated mice demonstrated the highest serum cytokine elicitation (TNF-α and IL-6). Likewise, a tail vein injection of Pachyman together with intraperitoneal lipopolysaccharide (LPS) induced the highest levels of these cytokines at 3 h post-injection than LPS alone or LPS with other BGs. With bone marrow-derived macrophages, BG induced only TNF-α (most prominent with Pachyman), while LPS with BG additively increased several cytokines (TNF-α, IL-6, and IL-10); inflammatory genes (iNOS, IL-1β, Syk, and NF-κB); and cell energy alterations (extracellular flux analysis). In conclusion, Pachyman induced the highest LPS proinflammatory synergistic effect on macrophages, followed by WGP, possibly through Syk-associated interactions between the Dectin-1 and TLR-4 signal transduction pathways. Selection of the proper form of BGs for specific clinical conditions might be beneficial.

Topics: Animals; Avena; beta-Glucans; Cytokines; Dextran Sulfate; Glucans; Interleukin-6; Lipopolysaccharides; Macrophages; Mice; Mucositis; Tumor Necrosis Factor-alpha

Methotrexate (MTX) is a widely used cancer chemotherapy agent. The efficacy of MTX is often limited by serious side effects, such as intestinal mucositis. The aim of this study was to evaluate the protective effect of water-soluble β-glucan salecan on MTX-induced intestinal toxicity in mice.. Intestinal mucositis was induced in C57BL/6 mice by intraperitoneal injection of MTX for two consecutive days. Mice were orally administrated with saline or salecan for 6 days before MTX injection and continued to the end of the study. Several histological and biochemical parameters were measured in the jejunum.. Orally administration of salecan improved the severity of intestinal mucositis in a dose-dependent manner, as evidenced by the well-maintained mucosal architecture and body weight in salecan-treated groups. Salecan treatment inhibited MTX-induced oxidative stress and effectively scavenged free radicals both in vitro and in vivo. Metabolomics analysis revealed that salecan treatment reversed the intestinal metabolic profiling changes in mice with MTX-induced mucositis. Salecan treatment modulated the innate immunity through the regulation of TLR and Dectin1 expression in the jejunum, thus protecting mice from MTX-induced intestinal damage.. Salecan has potential advantages in the treatment of MTX-induced intestinal mucositis, and its protective effect is mainly attributed to its antioxidant and immunomodulatory properties.

Topics: Administration, Oral; Animals; Antimetabolites, Antineoplastic; Antioxidants; beta-Glucans; Disease Models, Animal; Free Radical Scavengers; Immunity, Innate; Intestinal Mucosa; Male; Metabolomics; Methotrexate; Mice; Mice, Inbred C57BL; Mucositis; Oxidative Stress

Blood citrulline and intestinal fatty acid binding protein were determined as biomarkers for intestinal mucositis. Biomarker levels were correlated with corresponding serum 1,3-beta-D-glucan levels in 56 samples obtained from 33 cases with underlying hematological malignancies receiving induction chemotherapy. No correlation between biomarkers of intestinal mucositis and BDG levels was observed. (This study has been registered at ClinicalTrials.gov under registration no. NCT01576653.).

Topics: Adult; Aged; Antineoplastic Agents; beta-Glucans; Biomarkers; False Positive Reactions; Female; Hematologic Neoplasms; Humans; Intestinal Mucosa; Male; Middle Aged; Mucositis; Sensitivity and Specificity; Young Adult

The present study aimed to determine the effect of oral β-glucan on mucositis and leukopenia in 62 consecutive patients with colorectal cancer treated with an adjuvant FOLFOX-4 regimen. The patients were retrospectively evaluated in 2 groups: one group received β-glucan and the other did not (control group). Leucocytes, neutrophils, and platelets were evaluated before and 1 week after chemotherapy and oral mucositis and diarrhea were noted. Leucocyte and neutrophil counts after chemotherapy in the β-glucan group were 7,300/mm3 and 3,800/mm3, respectively, and the reductions, as compared to baseline, were not significant (p=0.673 and 0.784). The median platelet count was 264,000/mm3 after chemotherapy in the β-glucan group and the reduction, as compared to baseline, was borderline significant (p=0.048). In the control group, reduction in leucocyte, neutrophil, and platelet counts was statistically significant. Oral mucositis and diarrhea were less common in the β-glucan group. We conclude that β-glucan can be used to reduce the adverse effects of chemotherapy.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Chemotherapy, Adjuvant; Cohort Studies; Colorectal Neoplasms; Diarrhea; Female; Fluorouracil; Humans; Leucovorin; Leukocyte Count; Leukopenia; Male; Middle Aged; Mucositis; Organoplatinum Compounds; Platelet Count; Retrospective Studies; Stomatitis; Treatment Outcome

5-Fluorouracil and its derivatives are widely used in the treatment of a variety of tumours. However, their use is associated with gastrointestinal toxicity, myelotoxicity and immune toxicity. In this study, we examined the protective effects of low-molecular-weight beta-glucan isolated from Aureobasidium pullulans GM-NH-1A1 against toxicity of UFT (combination of tegafur (1-(2-tetrahydrofuryl)-5-fluorouracil) and uracil) in mice bearing colon 26 tumours.. UFT was administered orally at 50 mg/kg once daily for 14 days alone or with orally administered low-molecular-weight beta-glucan, 25, 50 and 100 mg/kg twice daily.. Tumour growth was inhibited equally in all treatment groups. Onset of diarrhoea, which started on day 9 of UFT administration, was delayed by concomitant administration of the beta-glucan (50 and 100 mg/kg twice daily). Histological analysis showed that damage to small-intestine villi by UFT was inhibited by the orally administered beta-glucan.. Oral administration of low-molecular-weight beta-glucan prevents gastrointestinal mucositis associated with UFT therapy without interfering with its anti-tumour activity.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Basidiomycota; beta-Glucans; Cell Line, Tumor; Drug Synergism; Intestinal Diseases; Intestinal Mucosa; Intestine, Small; Male; Mice; Mice, Inbred BALB C; Molecular Weight; Mucositis; Neoplasm Transplantation; Tegafur; Uracil