PMID- 23426538
OWN - NLM
STAT- MEDLINE
DCOM- 20130617
LR  - 20220311
IS  - 1128-3602 (Print)
IS  - 1128-3602 (Linking)
VI  - 17
IP  - 3
DP  - 2013 Feb
TI  - The role of intestinal mucosa oxidative stress in gut barrier dysfunction of 
      severe acute pancreatitis.
PG  - 349-55
LID - 3123 [pii]
AB  - BACKGROUND: Severe acute pancreatitis (SAP) is a serious systemic disease with a 
      sustained high mortality rate. Extensive evidence has shown that gut barrier 
      dysfunction plays a critical role in the pathophysiology of SAP. AIM: 
      Investigating the role of intestinal mucosa oxidative stress in gut barrier 
      dysfunction of SAP. MATERIALS AND METHODS: Twenty-four BALB/c mice were randomly 
      divided into two groups with twelve mice each group. The SAP group mice received 
      six intraperitoneal injections of cerulein (50 microg/kg) at 1-hour intervals, then 
      given one intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS from E. 
      coli) for inducing SAP. Normal saline was given to the mice of control group. The 
      animals of each group were averaged to two batches. Four and eight hours after 
      the final injection, respectively, mice were anesthetized and blood and tissue 
      samples were harvested for examination. The pathological changes of pancreas and 
      gut were observed and scored. The serum levels of diamine oxidase (DAO), amylase 
      and tumor necrosis factor-alpha (TNF-alpha) were measured. The contents of 
      malondialdehyde (MDA) and reduced glutathione (GSH) and activity of superoxide 
      dismutase (SOD) and xanthine oxidase (XO) in gut mucosa were detected. In gut 
      mucosa, the caspase-3 activity was measured and the cell apoptosis and apoptosis 
      index (AI) were determined by terminal deoxynucleotidyl transferase-mediated dUTP 
      nick end labeling (TUNEL) assay. The data were analyzed by ANOVA and t-test. 
      RESULTS: At four and eight hours after SAP induction, the SAP group mice had 
      significantly higher pancreatic and gut pathological scores (p < 0.01) and 
      increased serum levels of amylase (p < 0.05), DAO and TNF-alpha (p < 0.01) and 
      increased MDA contents and XO activity of gut mucosa (p < 0.01) compared with 
      those of control mice. There were significantly lower GSH contents (p < 0.05) and 
      SOD activity (p < 0.01) of gut mucosa in the SAP mice. It was also observed that 
      the gut mucosa cells of SAP mice had significantly higher caspase-3 activity and 
      apoptosis index (p < 0.01). CONCLUSIONS: In SAP, waterfall-style release of 
      inflammatory factors such as TNF-alpha led to ischemia-reperfusion injury of gut 
      mucosa which resulted in serious oxidative stress and activation of caspase-3 
      pathway and severe apoptosis of gut mucosa. Therefore, intestinal mucosal 
      oxidative stress may play an important role in the mechanism of gut barrier 
      dysfunction.
FAU - Tian, R
AU  - Tian R
AD  - Intensive Care Unit, First People's Hospital, Shanghai Jiaotong University, 
      Shanghai, China.
FAU - Tan, J-T
AU  - Tan JT
FAU - Wang, R-L
AU  - Wang RL
FAU - Xie, H
AU  - Xie H
FAU - Qian, Y-B
AU  - Qian YB
FAU - Yu, K-L
AU  - Yu KL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Inflammation Mediators)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 888Y08971B (Ceruletide)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Acute Disease
MH  - Analysis of Variance
MH  - Animals
MH  - Apoptosis
MH  - Caspase 3/metabolism
MH  - Ceruletide/toxicity
MH  - Disease Models, Animal
MH  - In Situ Nick-End Labeling
MH  - Inflammation Mediators/metabolism
MH  - Intestinal Mucosa/*physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - *Oxidative Stress
MH  - Pancreatitis/*physiopathology
MH  - Random Allocation
MH  - Reperfusion Injury/*physiopathology
MH  - Severity of Illness Index
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2013/02/22 06:00
MHDA- 2013/06/19 06:00
CRDT- 2013/02/22 06:00
PHST- 2013/02/22 06:00 [entrez]
PHST- 2013/02/22 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
AID - 3123 [pii]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2013 Feb;17(3):349-55.