Antioxidant inhibits HMGB1 expression and reduces pancreas injury in rats with severe acute pancreatitis.
BACKGROUND
Pathogenesis of severe acute pancreatitis is still unclear, which leads to a lack of proper treatment in severe acute pancreatitis therapeutic strategy.


OBJECTIVE
To investigate the effect of treatment with antioxidant pyrrolidine dithiocarbamate on pancreas injury in rats with severe acute pancreatitis and its possible mechanism.


METHODS
A total of 144 male Sprague-Dawley rats were randomly allocated into a sham operation group (n=48), a severe acute pancreatitis group (n=48), and a pyrrolidine dithiocarbamate-treated group (n=48). All the rats were killed at 1, 3, 6, 12, 24, and 48 h after operation. The pancreas histopathologies were observed and serum amylase levels were tested. Meanwhile, the nuclear factor-kappaB activation, tumor necrosis factor-alpha levels and high-mobility group box protein-1 expression levels in pancreatic tissue were studied.


RESULTS
Animals receiving pyrrolidine dithiocarbamate had significantly improved pancreas histopathology and lower serum amylase levels (p<0.05). In the severe acute pancreatitis group, pancreas tumor necrosis factor-alpha levels reached a peak at 6 h after operation and afterwards rapidly declined to normal levels. However, high-mobility group box protein-1 levels in pancreatic tissue increased remarkably at the 12th hour, reached a peak at 24 h, and maintained up to 48 h post-severe acute pancreatitis. Compared to the severe acute pancreatitis group, the pancreas nuclear factor-kappaB activity, tumor necrosis factor-alpha, high-mobility group box protein-1 levels in the pyrrolidine dithiocarbamate-treated group all remarkably decreased (p<0.05).


CONCLUSIONS
High-mobility group box protein-1 seems to act as a late cytokine mediator in the pathogenesis of severe acute pancreatitis. Pyrrolidine dithiocarbamate might inhibit the activation of nuclear factor-kappaB to blockade tumor necrosis factor-alpha, thereby indirectly suppressing the high-mobility group box protein-1 and reducing pancreatic tissue damage in rats with severe acute pancreatitis.
Zhang
Zhong Wei
ZW
Department of General Surgery, Shaoxing Second Hospital, 123 Yan'an Road, 312000, Shaoxing, Zhejiang province, China. zzwgood@163.com
Zhang
Qi Yu
QY
Zhou
Meng Tao
MT
Liu
Na Xin
NX
Chen
Tong Ke
TK
Zhu
Ye Fan
YF
Wu
Liang
L
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D024243:HMGB1 Protein / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013859:Thiocarbamates / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid; D000681:Amylases