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The traditional studies on the mechanisms of liver injury induced by IIR focused on the direct effect of toxic substances including proinflammatory cytokines, chemokines, and adhesion molecules on target organs. However, recent studies have shown a role of these mediators in gene regulation of the NF-闎 in liver injuries. [22,23] NF-闎 is a rapid response transcription factor in the cytoplasm and consists of two subunits of 50 kDa and 65 kDa that are bound to an inhibitor protein termed I闎. This phosphorylated inhibitor unit is tagged by ubiquitin for subsequent proteolysis, then the freed NF-闎 complex is thus able to translocate into the nucleus where they trans-activate target genes, [24] which is a common end-point of various signal transduction pathways. [25] In the early stage of intestinal ischemia/reperfusion, the gut barrier function is progressively damaged, and bacteria, endogenous endotoxin, bacteriotoxin and reactive oxygen species (ROS) invade into the circulation, and the low levels of ROS and inflammatory mediators can activate the expression of NF-闎. [26,27] In our study, 1-hour intestinal ischemia followed by 2-hour reperfusion not only injured the intestine itself, but also induced liver injury. The levels of AST, ALT and pathological injury increased significantly in the IR group but improved in the PDTC group; these were parallel to the levels of the NF-闎 p65. This finding suggested that the activation of NF-闎 be involved in the pathogenesis of liver injury induced by IIR. As a consequence, activated PMN and pro-inflammatory cytokines (TNF-? were released into the systemic circulation, interacting with the vascular endothelium of organs. Endothelial adhesion molecules expressed on the surface of endothelial cells such as ICAM-1 play a key role in neutrophil chemoattraction, adhesion, and emigration from the vasculature to the tissue, contributing to the systemic inflammatory response and organ injury. [28,29]

PDTC is an antioxidant. Recent studies have suggested that the pro-oxidant and metal-chelating properties of PDTC could also involve in its ability to inhibit NF-闎. [30-32] Some studies showed that PDTC may inhibit NF-闎 activation via stabilization of the I闎-?[26] or likely via inhibition of the ubiquitin-proteasome pathway. [33] In our study, PDTC attenuated acute liver injury induced by IIR; level of serum TNF-? liver oxides level; neutrophil infiltration (reflected by ICAM-1 expression); and expression of liver NF-闎 p65. These demonstrate that PDTC as an important antioxidant and inhibitor of NF-闎 prevents liver injury induced by IIR.

Funding: None.

Ethical approval: Not needed.

Contributors: TXF proposed the study and wrote the first draft. YJH and LYH analyzed the data. All authors contributed to the design and interpretation. TXF is the guarantor.

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

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