Preventive Effect of Daiokanzoto TJ-84 on 5-Fluorouracil-Induced Human Gingival Cell Death through the Inhibition of Reactive Oxygen Species ProductionReport as inadecuate




Preventive Effect of Daiokanzoto TJ-84 on 5-Fluorouracil-Induced Human Gingival Cell Death through the Inhibition of Reactive Oxygen Species Production - Download this document for free, or read online. Document in PDF available to download.

Daiokanzoto TJ-84 is a traditional Japanese herbal medicine Kampo formulation. While many Kampo formulations have been reported to regulate inflammation and immune responses in oral mucosa, there is no evidence to show that TJ-84 has beneficial effects on oral mucositis, a disease resulting from increased cell death induced by chemotherapeutic agents such as 5-fluorouracil 5-FU. In order to develop effective new therapeutic strategies for treating oral mucositis, we investigated i the mechanisms by which 5-FU induces the death of human gingival cells and ii the effects of TJ-84 on biological events induced by 5-FU. 5-FU-induced lactate dehydrogenase LDH release and pore formation in gingival cells Sa3 cell line resulted in cell death. Incubating the cells with 5-FU increased the expression of nucleotide-binding domain and leucine-rich repeat containing PYD-3 NLRP3 and caspase-1. The cleavage of caspase-1 was observed in 5-FU-treated cells, which was followed by an increased secretion of interleukin IL-1β. The inhibition of the NLRP3 pathway slightly decreased the effects of 5-FU on cell viability and LDH release, suggesting that NLRP3 may be in part involved in 5-FU-induced cell death. TJ-84 decreased 5-FU-induced LDH release and cell death and also significantly inhibited the depolarization of mitochondria and the up-regulation of 5-FU-induced reactive oxygen species ROS and nitric oxide NO production. The transcriptional factor, nuclear factor-κB NF-κB was not involved in the 5-FU-induced cell death in Sa3 cells. In conclusion, we provide evidence suggesting that the increase of ROS production in mitochondria, rather than NLRP3 activation, was considered to be associated with the cell death induced by 5-FU. The results also suggested that TJ-84 may attenuate 5-FU-induced cell death through the inhibition of mitochondrial ROS production.



Author: Kaya Yoshida , Masami Yoshioka, Hirohiko Okamura, Satomi Moriyama, Kazuyoshi Kawazoe, Daniel Grenier, Daisuke Hinode

Source: http://plos.srce.hr/



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