Suppressing progress of pancreatitis through selective inhibition of NF-KappaB activation by using NAC.
OBJECTIVE
To explore the characteristics of NF-KappaB activation in the progress of pancreatitis, the relationship with expression of TNF-alpha in the inflammatory reaction, and prevent the exacerbation of pancreatitis by using NAC.


METHODS
Forty-eight rats were divided into three groups: therapy (group C), pancreatitis (group B) and control (group A). NAC served as the inhibitor of NF-KappaB activation. In the time intervals of 1.5, 3.0, 6.0, 12.0 hour, NF-KappaB activation was detected with flow cytometry (FCM) and the expression of TNF-alpha mRNA and protein with in situ hybridization (ISH) and enzyme-linked immuno-sorbent assay (ELISA) respectively. Meanwhile, the level of lipase and amylase in the serum was assayed and the pathological change was evaluated.


RESULTS
NF-KappaB activation in the pancreatitis group was higher than that in the control group (P<0.01), peaked at 3 hours, and was depressed by the inhibitor of NF-KappaB, NAC. The expression of TNF-alpha as well as the level of lipase and amylase in the serum also rose synchronously with activation of NF-KappaB. In contrast to group A, it was significantly different (P<0.01) in group B. After using NAC in group C, all of these values were decreased and the inflammatory reaction in the pancreas abated evidently. The pathology changes of the pancreas were shown to be alleviated in group C.


CONCLUSIONS
First, NF-KappaB activity is intensively initiated in the course of pancreatitis and shown to have closely relationship with the release of cytokines. Second, use of NAC markedly depressed NF-KappaB activation. TNF-alpha expression is down regulated by cytokines. It is suggested that NAC probably acts as a useful agent for treatment of pancreatitis by indirectly inhibiting activation of NF-KappaB.
Zhao
Zhi-cheng
ZC
Dept. of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003, China. zc.zhao@163.com
Zheng
Shu-sen
SS
Cheng
Wen-liang
WL
Wang
Xuan
X
Qi
Ying
Y
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D017403:In Situ Hybridization; D016328:NF-kappa B / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000111:Acetylcysteine