title: Potential of sivelestat in protection against severe acute pancreatitis-associated lung injury in rats.
abstract: The incidence of acute pancreatitis has been rising worldwide in the past few decades. Despite extensive research efforts, the population-based mortality from acute pancreatitis remains high. Since dysfunction of multiple vital organs, most importantly the lungs, is the major cause of early death in acute pancreatitis patients, developing effective strategies to manage lung injury has become one of the focuses of recent research efforts aiming at improving the outcome of patients with acute pancreatitis. In this study, we attempted to create a rat model of acute pancreatitis through intraductal infusion of taurocholate and to evaluate the potential of sivelestat, a synthetic neutrophil elastase inhibitor, in protection against acute pancreatitis-associated lung injury using this rat model. The results demonstrated that: (1) 5% sodium taurocholate successfully induced histopathologic and biochemical abnormalities in the circulation, lung and pancreas characteristic of human acute pancreatitis, including an increase in amylase concentration and a decrease in partial arterial oxygen pressure (PaO2) in the blood, increases in activities of myeloperoxidase (MPO) (a lung injury marker) and neutrophil elastase (a quantitative indicator of neutrophil infiltration), and levels of malondialdehyde (an indicator of lipid peroxidation) and tumor necrosis factor-alpha (a major inflammatory mediator) in the lung; (2) intravenous administration of sivelestat effectively attenuated the taurocholate-induced abnormalities in all parameters analyzed except for serum amylase concentration. Our findings have validated the taurocholate model of acute pancreatitis and demonstrated great therapeutic potential for sivelestat in managing acute pancreatitis-associated lung injury.
authors.affiliation: Department of Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Hou-Hong
authors.initials: HH
authors.lastname: Wang
authors.forename: A-Mao
authors.initials: AM
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Meng-Tao
authors.initials: MT
authors.lastname: Zhou
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008168:Lung / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000150:complications* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D005998:Glycine