Protective effects of the free radical scavenger edaravone on acute pancreatitis-associated lung injury

• Published in: European journal of pharmacology Vol. 630; no. 1; pp. 152 - 157
• Main Authors: Yang, Tao, Mao, Yan-Fei, Liu, Shuang-Qing, Hou, Jiong, Cai, Zhi-Yang, Hu, Jin-Yu, Ni, Xin, Deng, Xiao-Ming, Zhu, Xiao-Yan
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.03.2010; Elsevier
• Subjects: Acute Lung Injury - etiology; Acute pancreatitis; Animals; Antipyrine - analogs & derivatives; Antipyrine - pharmacology; Biological and medical sciences; Disease Models, Animal; Edaravone; Free Radical Scavengers - pharmacology; Gastroenterology. Liver. Pancreas. Abdomen; Interleukin 6; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lung injury; Male; Medical sciences; Neutrophil infiltration; Other diseases. Semiology; Pancreatitis - complications; Pharmacology. Drug treatments; Protective Agents - pharmacology; Random Allocation; Rats; Rats, Sprague-Dawley; Tumor necrosis factor alpha; Interleukin 6; Tumor necrosis factor alpha; Acute pancreatitis; Edaravone; Neutrophil infiltration; Lung injury; Lung disease; Respiratory disease; Acute; Cytokine; Pancreatitis; Antioxidant; Radical scavenger; Free radical; Prevention; Digestive diseases; Neutrophil; Tumor necrosis factor α; Pancreatic disease
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2009.12.025

Impaired lung function is the primary contributor to most deaths associated with severe acute pancreatitis. It is widely accepted that oxidative stress plays a central role in the pathogenesis of pancreatitis and associated complications. Therefore, in the present study, we investigated whether therapeutic treatment with the free radical scavenger edaravone could protect rats against acute pancreatitis and the associated lung injury. Acute pancreatitis was induced by infusion of 1 ml/kg of sodium taurocholate (3% solution) into the biliopancreatic duct. Edaravone (8 mg/kg) was administered 1 h and 13 h after inducing pancreatitis, the severity of pancreatic and pulmonary injuries was evaluated 24 h after inducing pancreatitis. Edaravone treatment significantly reduced the elevated malondialdehyde levels in rat lungs after acute pancreatitis, suggesting an important role for free radicals in acute pancreatitis-associated lung injury. In addition, edaravone showed significant protective effects against neutrophil infiltration and tissue injury in both pancreas and lung, as demonstrated by serum amylase levels, myeloperoxidase activity and histopathological analysis. Edaravone treatment also attenuated the elevated mRNA levels of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) in rat lungs after acute pancreatitis. In conclusion, edaravone protects rats against acute pancreatitis-associated lung injury, probably through its antioxidant and anti-inflammatory effects. Thus, edaravone shows promise as a treatment for lung injury in patients with acute pancreatitis.