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Cancer Chemotherapy and Pharmacology

, Volume 84, Issue 1, pp 105–116 | Cite as

Orally administered salecan ameliorates methotrexate-induced intestinal mucositis in mice

  • Yan Gao
  • Qi Sun
  • Xiao Yang
  • Weiling Lu
  • Yang Zhao
  • Wenhao Ge
  • Yunxia Yang
  • Xi Xu
  • Jianfa ZhangEmail author
Original Article
  • 54 Downloads

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.

Keywords

Methotrexate Intestine mucositis Salecan Antioxidant Metabonomics 

Notes

Acknowledgements

This work was supported by the grant from National Nature Science Foundation of China (Numbers 31671220, 31471111).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

280_2019_3854_MOESM1_ESM.pdf (91 kb)
Supplementary material 1 (PDF 90 kb)
280_2019_3854_MOESM2_ESM.tif (160 kb)
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_MOESM3_ESM.tif (598 kb)
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)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Yan Gao
    • 1
  • Qi Sun
    • 1
  • Xiao Yang
    • 1
  • Weiling Lu
    • 1
  • Yang Zhao
    • 1
  • Wenhao Ge
    • 1
  • Yunxia Yang
    • 1
  • Xi Xu
    • 1
  • Jianfa Zhang
    • 1
    Email author
  1. 1.Center for Molecular Metabolism, Nanjing University of Science and TechnologyNanjingPeople’s Republic of China

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