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TU-100 exerts a protective effect against bacterial translocation by maintaining the tight junction

Surgery Today volume 47, pages 1287–1294 (2017)Cite this article

Abstract

Purpose

We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT.

Methods

Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i.p. for 2 days), and the CPT-11 and TU-100 co-treated group (1000 mg/kg, p.o. for 5 days). All of the rats were sacrificed on day 6 and their tissues were collected.

Results

CPT-11 and TU-100 co-treatment improved CPT-11 the related cytotoxicity in vitro. All CPT-11-treated rats developed different grades of diarrhea and BT was observed in 80% of the rats. CPT-11 caused a significant increase in the expression of TLR4, IL-6, TNF-α, IL-1β and caspase-3 mRNAs in the large intestine. The expression of tight junction (TJ) marker mRNAs (occludin, claudin-1 and 4, and ZO-1) was significantly decreased in comparison to the control group. TU-100 co-treatment significantly reversed diarrhea, BT, and the expression of TLR2, IL-6, TNF-α, IL-1β and caspase-3, and improved the expression of occludin, claudin-4 and ZO-1.

Conclusions

TU-100 can suppress the adverse effects associated with CPT-11 and improve the function of the TJ. It is possible that this occurs through the TLR pathway.

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Acknowledgements

This study was supported by a Grant from the Tsumura. & Co. and Cancer Research Project a cooperative project of the TAIHO Pharmaceutical Co., Ltd. and the University of Tokushima, and by the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research C: No. 22591489 and Research B: No. 23791536).

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Affiliations

  1. Departments of Surgery, Institute of Health Biosciences, Tokushima University, Kuramoto 3-18-15, Tokushima, 770-8503, Japan

    Chie Takasu, Wubetu Gizachew Yismaw, Nobuhiro Kurita, Kozo Yoshikawa, Hideya Kashihara & Mitsuo Shimada

  2. Center for Clinical and Biomedical Research, Sapporo Hisgashi Tokushukai Hospital, Hokkaido, Japan

    Toru Kono

Authors
  1. Chie Takasu
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  2. Wubetu Gizachew Yismaw
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  3. Nobuhiro Kurita
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  4. Kozo Yoshikawa
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  5. Hideya Kashihara
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  6. Toru Kono
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  7. Mitsuo Shimada
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Corresponding author

Correspondence to Chie Takasu.

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Conflict of interest

This study was supported by a Grant from the Tsumura. & Co. and Cancer Research Project a cooperative project of the TAIHO Pharmaceutical Co., Ltd. and the University of Tokushima, and by the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research C: No. 22591489 and Research B: No. 23791536). Mitsuo Shimada received a research Grant from Taiho Pharmaceutical Co. Ltd. The other authors declare no conflicts of interest in association with the present study.

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Takasu, C., Yismaw, W.G., Kurita, N. et al. TU-100 exerts a protective effect against bacterial translocation by maintaining the tight junction. Surg Today 47, 1287–1294 (2017). https://doi.org/10.1007/s00595-017-1518-6

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  • DOI: https://doi.org/10.1007/s00595-017-1518-6

Keywords

  • Kampo
  • Inflammatory cytokine
  • Toll-like-receptor