Pyrrolidine Dithiocarbamate Inhibits Nuclear Factor κB and Toll-Like Receptor 4 Expression in Rats with Acute Necrotizing Pancreatitis

Background/Aims: To investigate the expression of Toll-like receptor 4 (TLR4) in the pancreases of rats with acute necrotizing pancreatitis (ANP) and any changes upon treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappa B (NF-kappa B), as well as to determine the relationship between TLR4 and NF-kappa B in ANP pathogenesis. Methods: A total of 72 SD rats were randomly divided into three groups, namely, the control (sham-operation), ANP, and ANP with PDTC pretreatment groups. The PDTC-pretreated group was intraperitoneally injected with PDTC at a dose of 100 mg/kg 1 hour before the induction of ANP. The expressions of TLR4 and NF-kappa B in pancreatic tissue were evaluated by immunohistochei-nistry and Western blot analysis. The mRNA levels of cytokines tumor necrosis factor a, interleukin (IL)-1 beta, and IL-6 were measured by reverse transcription polymerase chain reaction. Results: The expressions of TLR4, NF-kappa beta, and cytokine (NF-kappa B target) genes in the pancreatic tissue increased more significantly in the ANP groups than in the sham-operation group at 3, 6, and 12 hours. Pretreatment with PDTC alleviated the inflammatory activation in the pancreas with ANP, causing a significant decrease in the expressions of TLR4, NF-kappa B, and cytokine genes in the pancreatic tissue. Conclusions: The expressions of TLR4 and NF-kappa B were increased in the pancreases of rats with ANP. PDTC not only inhibits NF-kappa B but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.