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

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.

• Authors: Chie Takasu, Wubetu Gizachew Yismaw, Nobuhiro Kurita, Kozo Yoshikawa, Hideya Kashihara, Toru Kono, Mitsuo Shimada
• Journal: Surgery today (Surg Today) Vol. 47 Issue 10 Pg. 1287-1294 (Oct 2017) ISSN: 1436-2813 [Electronic] Japan
• PMID: 28421347 (Publication Type: Journal Article)

Chemical References

• 12,13-dihydro-N-methyl-6,11,13-trioxo-5H-benzo(4,5)cyclohepta(1,2-b)naphthalen-5,12-imine
• Antineoplastic Agents, Phytogenic
• Claudin-4
• Cytokines
• Inflammation Mediators
• Naphthoquinones
• Occludin
• Toll-Like Receptors
• Zonula Occludens-1 Protein
• Irinotecan
• Camptothecin

Topics

• Animals
• Antineoplastic Agents, Phytogenic (adverse effects)
• Bacterial Translocation (drug effects)
• Camptothecin (adverse effects, analogs & derivatives, antagonists & inhibitors)
• Cells, Cultured
• Claudin-4 (metabolism)
• Cytokines (metabolism)
• Diarrhea (chemically induced, drug therapy)
• Humans
• Inflammation Mediators (metabolism)
• Irinotecan
• Male
• Naphthoquinones (pharmacology, therapeutic use)
• Occludin (metabolism)
• Phytotherapy
• Rats, Wistar
• Tight Junctions (microbiology)
• Toll-Like Receptors (physiology)
• Zonula Occludens-1 Protein (metabolism)