Gut Liver.  2015 May;9(3):411-416. 10.5009/gnl14050.

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

• Xu M
• Wang KN
• Wu K
• Wang XP

• KMID: 2155650
• DOI: http://doi.org/10.5009/gnl14050

Abstract

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 kappaB (NF-kappaB), as well as to determine the relationship between TLR4 and NF-kappaB 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-kappaB in pancreatic tissue were evaluated by immunohistochemistry and Western blot analysis. The mRNA levels of cytokines tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 were measured by reverse transcription polymerase chain reaction.
RESULTS
The expressions of TLR4, NF-kappaB, and cytokine (NF-kappaB 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-kappaB, and cytokine genes in the pancreatic tissue.
CONCLUSIONS
The expressions of TLR4 and NF-kappaB were increased in the pancreases of rats with ANP. PDTC not only inhibits NF-kappaB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.

Keyword

Acute necrotizing pancreatitis; NF-kappa B; Toll-like receptor 4

MeSH Terms

Animals
Antioxidants/*pharmacology
Interleukin-1beta/genetics/metabolism
Interleukin-6/genetics/metabolism
Male
NF-kappa B/*drug effects/metabolism
Pancreas/metabolism/pathology
Pancreatitis, Acute Necrotizing/chemically induced/*drug therapy
Pyrrolidines/*pharmacology
RNA, Messenger/metabolism
Random Allocation
Rats
Rats, Sprague-Dawley
Thiocarbamates/*pharmacology
Toll-Like Receptor 4/*drug effects/metabolism
Tumor Necrosis Factor-alpha/genetics/metabolism
Antioxidants
Interleukin-1beta
Interleukin-6
NF-kappa B
Pyrrolidines
RNA, Messenger
Thiocarbamates
Toll-Like Receptor 4
Tumor Necrosis Factor-alpha