title: Ethyl pyruvate significantly inhibits tumour necrosis factor-α, interleukin-1β and high mobility group box 1 releasing and attenuates sodium taurocholate-induced severe acute pancreatitis associated with acute lung injury.
abstract: In this study, we examined the effect of ethyl pyruvate (EP) on pulmonary inflammation in rats with severe pancreatitis-associated acute lung injury (ALI). Severe acute pancreatitis (SAP) was induced in rats by the retrograde injection of 5% sodium taurocholate into the pancreatic duct. Rats were randomly divided into the following experimental groups: control group, SAP group and EP-treated group. The tissue specimens were harvested for morphological studies, Streptavidin-peroxidase immunohistochemistry examination. Pancreatic or lung tissue oedema was evaluated by tissue water content. Serum amylase and lung tissue malondialdehyde (MDA) and myeloperoxidase (MPO) were measured. Meanwhile, the nuclear factor-κB (NF-κB) activation, tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels and HMGB1 protein expression levels in the lung were studied. In the present study, we demonstrated that treatment with EP after SAP was associated with a reduction in the severity of SAP and lung injury. Treatment with EP significantly decreased the expression of TNF-α, IL-1β, HMGB1 and ameliorated MDA concentration, MPO activity in the lung in SAP rats. Compared to SAP group, administration of EP prevented pancreatitis-induced increases in nuclear translocation of NF-κB in the lung. Similarly, treatment with EP significantly decreased the accumulation of neutrophils and markedly reduced the enhanced lung permeability. In conclusion, these results demonstrate that EP might play a therapeutic role in pulmonary inflammation in this SAP model.
authors.affiliation: Department of Intensive Care Unit, The First Hospital, China Medical University, Shenyang, China.
authors.forename: Z-G
authors.initials: ZG
authors.lastname: Luan
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: X-H
authors.initials: XH
authors.lastname: Yin
authors.forename: X-C
authors.initials: XC
authors.lastname: Ma
authors.forename: R-X
authors.initials: RX
authors.lastname: Guo
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D000681:Amylases / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010195:Pancreatitis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D011773:Pyruvates / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D053583:Interleukin-1beta; D011773:Pyruvates; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate; D008315:Malondialdehyde; D013656:Taurocholic Acid; D009195:Peroxidase; D000681:Amylases