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TU-100 exerts a protective effect against bacterial translocation by maintaining the tight junction
- Source :
- Surgery Today. 47:1287-1294
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- 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. 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. 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. 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.
- Subjects :
- Diarrhea
Male
Biology
Pharmacology
Irinotecan
Occludin
Tight Junctions
Proinflammatory cytokine
03 medical and health sciences
0302 clinical medicine
In vivo
Animals
Humans
Claudin-4
Rats, Wistar
Cells, Cultured
Tight junction
Toll-Like Receptors
General Medicine
Antineoplastic Agents, Phytogenic
digestive system diseases
In vitro
TLR2
Apoptosis
Bacterial Translocation
030220 oncology & carcinogenesis
Zonula Occludens-1 Protein
TLR4
Cytokines
Camptothecin
030211 gastroenterology & hepatology
Surgery
Inflammation Mediators
Naphthoquinones
Phytotherapy
Subjects
Details
- ISSN :
- 14362813 and 09411291
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- Surgery Today
- Accession number :
- edsair.doi.dedup.....ee4c84cc1bcefa1ccec867eba5bc57d0