Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats.
OBJECTIVE
To investigate the effect of delayed ethyl pyruvate (EP) delivery on distant organ injury, survival time and serum high mobility group box 1 (HMGB1) levels in rats with experimental severe acute pancreatitis (SAP).


METHODS
A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups (n = 32 in each group): sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP (30 mg/kg) at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels were measured. Lung wet-to-dry-weight (W/D) ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats.


RESULTS
Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios (8.22 +/- 0.42 vs 9.76 +/- 0.45, P < 0.01), pulmonary histological scores (7.1 +/- 0.7 vs 8.4 +/- 1.1, P < 0.01), serum AST (667 +/- 103 vs 1 368 +/- 271, P < 0.01), ALT (446 +/- 91 vs 653 +/- 98, P < 0.01) and Cr (1.2 +/- 0.3 vs 1.8 +/- 0.3, P < 0.01) levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h (P < 0.01).


CONCLUSIONS
Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGB1levels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome (MODS) in SAP patients.
Yang
Zhi-Yong
ZY
Department of Pancreatic Surgery, Huazhong University of Sciecne and Technology, China.
Ling
Yan
Y
Yin
Tao
T
Tao
Jing
J
Xiong
Jiong-Xin
JX
Wu
He-Shui
HS
Wang
Chun-You
CY
D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000097:blood*; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000503:physiopathology; D008099:Liver / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology; D008297:Male; D010195:Pancreatitis / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy*; D011773:Pyruvates / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D024243:HMGB1 Protein; D011773:Pyruvates; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase