Potential protective effect of nuclear factor-κB decoy oligodeoxynucleotides on endotoxin-induced liver injury.

PURPOSE

We sought to study the protective effects of nuclear factor-κB decoy oligodeoxynucleotides (ODNs) on endotoxin-induced liver injury in a rat model.

METHODS

Sixty Sprague-Dawley rats were randomly divided into a control (n=20), a lipopolysaccharide (LPS) (n=20), and an NF-κB decoy ODN group (n=20). Liver and blood serum samples were collected at 24 hours after the operation. NF-κB binding activity was detected by an electrophoretic mobility shift assay, liver histopathology, by light microscopy; and cell apoptosis, by a terminal-deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay. The serum of liver enzyme (aspartate transaminase [AST]) levels were measured using an automated biochemical analyzer and tumor necrosis factor (TNF)-α and interleukin (IL)-6 by enzyme-linked immunosorbent assays.

RESULTS

NF-κB was dramatically activated after endotoxin-induced liver injury. Many hepatocytes underwent degeneration and necrosis in the LPS group. The expressions of AST, TNF-α, and IL-6 were significantly increased compared with the control group (P=.0005), However, NF-κB decoy ODNs altered these undesirable changes. On the other hand, IL-6 expression was not significantly decreased by the NF-κB decoy versus the LPS group (P=.0745).

CONCLUSIONS

NF-κB decoy strategy inhibited the binding activity of NF-κB, thus suppressing production of downstream cytokines which play crucial roles in protection from endotoxin-induced injury.