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08.05.2019 | Original Article | Ausgabe 1/2019

Cancer Chemotherapy and Pharmacology 1/2019

Orally administered salecan ameliorates methotrexate-induced intestinal mucositis in mice

Zeitschrift:
Cancer Chemotherapy and Pharmacology > Ausgabe 1/2019
Autoren:
Yan Gao, Qi Sun, Xiao Yang, Weiling Lu, Yang Zhao, Wenhao Ge, Yunxia Yang, Xi Xu, Jianfa Zhang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00280-019-03854-x) contains supplementary material, which is available to authorized users.

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Zusatzmaterial
Supplementary material 1 (PDF 90 kb)
280_2019_3854_MOESM1_ESM.pdf
Supplementary Fig. 1 The relative viability of B16F10 cells after being exposed to MTX and salecan at different concentrations for 24 h by a MTT assay. Data are shown as the mean ± SEM, n = 6, #p < 0.05, ##p < 0.01, compared to control group; *p < 0.05, **p < 0.01, compared to MTX (10 μg/ml) group. (TIFF 159 kb)
280_2019_3854_MOESM2_ESM.tif
Supplementary Fig. 2 Typical 500 MHz 1H NMR spectra of the small intestine of mice from the control group, MTX group, and high-dose salecan group were in black, green and red, respectively. Labeled metabolites: 1. Isoleucine, 2. Leucine, 3. Valine, 4. Lactate, 5. Threonine, 6. Alanine, 7. Lysine, 8. Acetate, 9. Glutamate, 10. Glutathione, 11. Succinate, 12. Methionine, 13. Creatine phosphate, 14. O-Phosphocholine, 15. Taurine, 16. Glycine, 17. Glucose, 18. Uridine, 19. Inosine, 20. Fumarate, 21. Tyrosine, 22. Phenylalanine, 23. Histidine, 24. 3-Methylxanthine, 25. Adenosine, 26. AMP. (TIFF 597 kb)
280_2019_3854_MOESM3_ESM.tif
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