Antithrombin III prevents cerulein-induced acute pancreatitis in rats.
OBJECTIVE
Systemic inflammatory mediators, including the protein high-mobility group box 1 (HMGB1), play an important role in the development of acute pancreatitis. Anticoagulants, such as antithrombin III (AT III), inhibit inflammation resulting from various causes, but their mechanism of action is not well understood. Because acute pancreatitis is a severe inflammatory disease, we hypothesized that AT III would inhibit inflammation and prevent cerulein-induced acute pancreatitis.


METHODS
Experimental animals received or were saline injected with a bolus of 250 IU/kg of AT III followed by intraperitoneal injections of 50 mg/kg of cerulein. Levels of cytokines (interleukin 6 and tumor necrosis factor alpha), nitric oxide (NO), and HMGB1 were measured in serum and pancreatic tissue at regular intervals for 12 hours after the cerulein injection.


RESULTS
Pancreas histopathology and wet-dry ratio significantly improved in the AT III-injected (250 IU/kg) animals compared with the saline-injected rats. Serum and pancreas HMGB1 levels decreased over time in AT III-treated animals. Antithrombin III also decreased cytokine, NO, and HMGB1 levels during cerulein-induced inflammation. As a result, AT III ameliorated the pathologic pancreas in the rat model of cerulein-induced acute pancreatitis.


CONCLUSIONS
Antithrombin III treatment inhibited the secretion of cytokines, NO, and HMGB1 and prevented cerulein-induced acute pancreatitis in the rat model.
Hagiwara
Satoshi
S
Departments of Anesthesiology and Intensive Care Medicine, Oita University, Yufu City, Japan. saku@med.oita-u.ac.jp
Iwasaka
Hideo
H
Shingu
Chihiro
C
Matsumoto
Shigekiyo
S
Uchida
Tomohisa
T
Noguchi
Takayuki
T
D000208:Acute Disease; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000990:Antithrombin III / Q000494:pharmacology*; D015153:Blotting, Western; D002108:Ceruletide; D024243:HMGB1 Protein / Q000097:blood / Q000378:metabolism; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000925:Anticoagulants; D024243:HMGB1 Protein; D015850:Interleukin-6; D009569:Nitric Oxide; D002108:Ceruletide; D000990:Antithrombin III