title: Pretreatment with low doses of acenocoumarol inhibits the development of acute ischemia/reperfusion-induced pancreatitis.
abstract: Coagulative disorders are known to occur in acute pancreatitis and are related to the severity of this disease. Various experimental and clinical studies have shown protective and therapeutic effect of heparin in acute pancreatitis. Aim of the present study was to determine the influence of acenocoumarol, a vitamin K antagonist, on the development of acute pancreatitis. Studies were performed on male Wistar rats weighing 250 - 270 g. Acenocoumarol at the dose of 50, 100 or 150 μg/kg/dose or vehicle were administered once a day for 7 days before induction of acute pancreatitis. Acute pancreatitis was induced in rats by pancreatic ischemia followed by reperfusion. The severity of acute pancreatitis was assessed after 5-h reperfusion. Pretreatment with acenocoumarol given at the dose of 50 or 100 μg/kg/dose reduced morphological signs of acute pancreatitis. These effects were accompanied with a decrease in the pancreatitis-evoked increase in serum activity of lipase and serum concentration of pro-inflammatory interleukin-1β. Moreover, the pancreatitis-evoked reductions in pancreatic DNA synthesis and pancreatic blood flow were partially reversed by pretreatment with acenocoumarol given at the dose of 50 and 100 μg/kg/dose. Administration of acenocoumarol at the dose of 150 μg/kg/dose did not exhibit any protective effect against ischemia/reperfusion-induced pancreatitis. We concluded that pretreatment with low doses of acenocoumarol reduces the severity of ischemia/reperfusion-induced acute pancreatitis.
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland. mpwarzec@cyf-kr.edu.pl.
authors.forename: Z
authors.initials: Z
authors.lastname: Warzecha
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.|Department of Anesthesiology and Intensive Therapy, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Sendur
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Ceranowicz
authors.affiliation: The Second Department of General Surgery, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Dembinski
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Cieszkowski
authors.affiliation: Department of Clinical Biochemistry, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Kusnierz-Cabala
authors.affiliation: Department of Pathology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Tomaszewska
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Dembinski
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage / Q000494:pharmacology*; D000208:Acute Disease; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D053583:Interleukin-1beta / Q000097:blood; D008049:Lipase / Q000097:blood; D008297:Male; D010195:Pancreatitis / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy*; D012720:Severity of Illness Index
chemical_list: D000925:Anticoagulants; D053583:Interleukin-1beta; D004247:DNA; D008049:Lipase; D000074:Acenocoumarol