Effect of echinacoside as a palliative for irinotecan-induced intestinal mucositis
DOI:
https://doi.org/10.33910/2687-1270-2023-4-4-429-440Keywords:
irinotecan, anticancer, intestinal inflammation, echinacosides, diarrheaAbstract
Irinotecan, an anticancer drug, causes severe delayed diarrhea due to its active metabolite, SN-38, which damages the intestinal mucosa. This diarrhea may lead to the discontinuation of anticancer therapy in clinical practice. Therefore, in this study, we aimed to elucidate the pathogenesis of irinotecan-induced intestinal inflammation. We examined the effects of echinacoside, which has been reported to reduce LPS (lipopolysaccharide)-induced apoptosis and inflammation. We administered irinotecan (75 mg/kg) to seven-week-old male BALB/c mice intraperitoneally once daily for 4 d; a daily decrease in body weight, and no diarrhea was observed. Necropsies were performed 24 and 72 h after the last dose. Irinotecan caused cellular damage in the small intestine, particularly the ileum. After 72 h, a significant increase in myeloperoxidase activity was observed in the ileum. Concomitant oral administration of echinacoside (500 and 1000 mg/kg) with irinotecan significantly prevented weight loss and cellular damage in the ileal region. These results suggested the role of intestinal bacteria as previously reported with 5-FU-induced enteritis. The increased rate of deconjugation by β-glucuronidase may have increased the direct damage caused by SN-38. Additionally, irinotecan caused less histological damage to the large intestine than to the small intestine, possibly explaining the clinical absence of diarrhea. In conclusion, concomitant administration of echinacoside significantly inhibited the severity of irinotecan-induced intestinal inflammation, indicating their usefulness against irinotecan-induced enteritis.
References
Andrade, M. E. R., Trindade, L. M., Leocádio, P. C. L. et al. (2023) Association of fructo-oligosaccharides and arginine improves severity of mucositis and modulate the intestinal microbiota. Probiotics and Antimicrobial Proteins, vol. 15, no. 2, pp. 424–440. https://www.doi.org/10.1007/s12602-022-10032-8 (In English)
Andreyev, J., Ross, P., Donnellan, C. et al. (2014) Guidance on the management of diarrhoea during cancer chemotherapy. Lancet Oncology, vol. 15, no. 10, pp. e447–e460. https://www.doi.org/10.1016/S1470-2045(14)70006-3 (In English)
Bastos, R. W., Pedroso, S. H., Vieira, A. T. et al. (2016) Saccharomyces cerevisiae UFMG A-905 treatment reduces intestinal damage in a murine model of irinotecan-induced mucositis. Beneficial Microbes, vol. 7, no. 4, pp. 549–557. https://www.doi.org/10.3920/BM2015.0190 (In English)
Bauer, R. (1998) Echinacea: Biological effects and active principles. In: L. D. Lawson, R. Bauer (eds.). Phytomedicines of Europe: Chemistry and Biological Activity. Washington: American Chemical Society Publ., pp. 140–157. (In English)
Boeing, T., de Souza, P., Speca, S. et al. (2020) Luteolin prevents irinotecan-induced intestinal mucositis in mice through antioxidant and anti-inflammatory properties. British Journal of Pharmacology, vol. 177, no. 10, pp. 2393–2408. https://www.doi.org/10.1111/bph.14987 (In English)
Bowen, J. M., Gibson, R. J., Cummins, A. G. et al. (2006) Intestinal mucositis: The role of the Bcl-2 family, p53 and caspases in chemotherapy-induced damage. Support Care in Cancer, vol. 14, no. 7, pp. 713–731. https://www.doi.org/10.1007/s00520-005-0004-7 (In English)
Brevoort, P. (1998) The booming U.S. botanical market: A new overview. HerbalGram, vol. 44, pp. 33–46. (In English)
Cai, R.-L., Yang, M.-H., Shi, Y. et al. (2010) Antifatigue activity of phenylethanoid-rich extract from Cistanche deserticola. Phytotherapy Research, vol. 24, no. 2, pp. 313–315. https://www.doi.org/10.1002/ptr.2927 (In English)
Dancey, J., Eisenhauer, E. A. (1996) Current perspectives on camptothecins in cancer treatment. British Journal of Cancer, vol. 74, no. 3, pp. 327–338. https://www.doi.org/10.1038/bjc.1996.362 (In English)
Dong, L., Wang, H., Niu, J. et al. (2015) Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1. OncoTargets and Therapy, vol. 8, pp. 3649–3664. https://www.doi.org/10.2147/OTT.S94513 (In English)
Fassberg, J., Stella, V. J. (1992) A kinetic and mechanistic study of the hydrolysis of camptothecin and some analogues. Journal of Pharmaceutical Sciences, vol. 81, no. 7, pp. 676–684. https://www.doi.org/10.1002/jps.2600810718 (In English)
Gauthier, R., Harnois, C., Drolet, J. F. et al. (2001a) Human intestinal epithelial cell survival: Differentiation state-specific control mechanisms. American Journal of Physiology. Cell Physiology, vol. 280, no. 6, pp. C1540–C1554. https://pubmed.ncbi.nlm.nih.gov/11350749 (In English)
Gauthier, R., Laprise, P., Cardin, É. et al. (2001b) Differential sensitivity to apoptosis between the human small and large intestinal mucosae: Linkage with segment-specific regulation of Bcl-2 homologs and involvement of signaling pathways. Journal of Cellular Biochemistry, vol. 82, no. 2, pp. 339–355. https://www.doi.org/10.1002/jcb.1172 (In English)
Iyer, L., King, C. D., Whitington, P. F. et al. (1998) Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes. Journal of Clinical Investigation, vol. 101, no. 4, pp. 847–854. https://www.doi.org/10.1172/JCI915 (In English)
Jia, Y., Guan, Q., Guo, Y., Du, C. (2012) Echinacoside stimulates cell proliferation and prevents cell apoptosis in intestinal epithelial MODE-K cells by up-regulation of transforming growth factor-β1 expression. Journal of Pharmacological Sciences, vol. 118, no. 1, pp. 99–108. https://www.doi.org/10.1254/jphs.11186FP (In English)
Jonan, S., Hamouda, N., Fujiwara, A. et al. (2022) Alleviative effects of glutamate against chemotherapeutic agent-induced intestinal mucositis. Journal of Physiology and Pharmacology, vol. 73, no. 4, pp. 539–546. https://www.doi.org/10.26402/jpp.2022.4.07 (In English)
Keefe, D. M., Elting, L. S., Nguyen, H. T. et al. (2014) Risk and outcomes of chemotherapy-induced diarrhea (CID) among patients with colorectal cancer receiving multi-cycle chemotherapy. Cancer Chemotherapy and Pharmacology, vol. 74, no. 4, pp. 675–680. https://www.doi.org/10.1007/s00280-014-2526-5 (In English)
Kobayashi, K., Bouscarel, B., Matsuzaki, Y. et al. (1999) pH-dependent uptake of irinotecan and its active metabolite, SN-38, by intestinal cells. International Journal of Cancer, vol. 83, no. 4, pp. 491–496. https://doi.org/10.1002/(sici)1097-0215(19991112)83:4%3C491::aid-ijc10%3E3.0.co;2-m (In English)
Lalla, R. V., Bowen, J., Barasch, A. et al. (2014) MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer, vol. 120, no. 10, pp. 1453–1461. https://doi.org/10.1002/cncr.28592 (In English)
Li, L., Wan, G., Han, B. et al. (2018) Echinacoside alleviated LPS-induced cell apoptosis and inflammation in rat intestine epithelial cells by inhibiting the mTOR/STAT3 pathway. Biomedicine & Pharmacotherapy, vol. 104, pp. 622–628. https://doi.org/10.1016/j.biopha.2018.05.072 (In English)
Lian, Q., Xu, J., Yan, S. et al. (2017) Chemotherapy-induced intestinal inflammatory responses are mediated by exosome secretion of double-strand DNA via AIM2 inflammasome activation. Cell Research, vol. 27, no. 6, pp. 784–800. https://doi.org/10.1038/cr.2017.54 (In English)
Ribeiro, R. A., Wanderley, C. W. S, Wong, D. V. T. et al. (2016) Irinotecan- and 5-fluorouracil-induced intestinal mucositis: Insights into pathogenesis and therapeutic perspectives. Cancer Chemotherapy and Pharmacology, vol. 78, no. 5, pp. 881–893. https://doi.org/10.1007/s00280-016-3139-y (In English)
Ringel-Kulka, T., Choi, C. H., Temas, D. et al. (2015) Altered colonic bacterial fermentation as a potential pathophysiological factor in irritable bowel syndrome. American Journal of Gastroenterology, vol. 110, no. 9, pp. 1339–1346. https://doi.org/10.1038/ajg.2015.220 (In English)
Roberts, A. B., Wallace, B. D., Venkatesh, M. K. et al. (2013) Molecular insights into microbial β-glucuronidase inhibition to abrogate CPT-11 toxicity. Molecular Pharmacology, vol. 84, no. 2, pp. 208–217. https://doi.org/10.1124/mol.113.085852 (In English)
Sezer, A., Usta, U., Cicin, I. (2009) The effect of Saccharomyces boulardii on reducing irinotecan-induced intestinal mucositis and diarrhea. Medical Oncology, vol. 26, no. 3, pp. 350–357. https://doi.org/10.1007/s12032-008-9128-1 (In English)
Stringer, A. M., Gibson, R. J., Logan, R. M. et al. (2008) Faecal microflora and beta-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats. Cancer Biology & Therapy, vol. 7, no. 12, pp. 1919–1925. https://doi.org/10.4161/cbt.7.12.6940 (In English)
Takasuna, K., Hagiwara, T., Hirohashi, M. et al. (1996) Involvement of beta-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats. Cancer Research, vol. 56, no. 16, pp. 3752–3757. https://pubmed.ncbi.nlm.nih.gov/8706020 (In English)
Wang, Y.-H., Xuan, Z.-H., Tian, S. et al. (2015) Echinacoside protects against 6-hydroxydopamine-induced mitochondrial dysfunction and inflammatory responses in PC12 cells via reducing ROS production. Evidence-Based Complementary and Alternative Medicine, vol. 2015, article 189239. https://doi.org/10.1155/2015/189239 (In English)
Zhang, D., Lu, C., Yu, Z. et al. (2017) Echinacoside alleviates UVB irradiation-mediated skin damage via inhibition of oxidative stress, DNA damage, and apoptosis. Oxidative Medicine and Cellular Longevity, vol. 2017, article 6851464. https://doi.org/10.1155/2017/6851464 (In English)
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Hikaru Otsuki, Shizuka Jonan, Taisei Tsujii, Nahla Hamouda, Kikuko Amagase
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The work is provided under the terms of the Public Offer and of Creative Commons public license Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). This license allows an unlimited number of persons to reproduce and share the Licensed Material in all media and formats. Any use of the Licensed Material shall contain an identification of its Creator(s) and must be for non-commercial purposes only.
