Influence of nitric oxide-donating nonsteroidal anti-inflammatory drugs on the evolution of acute pancreatitis

Shock
Laura Iris Cosen-BinkerOsvaldo Tiscornia

Abstract

Microcirculatory disturbances and leukocyte activation are main events in the pathogenesis of acute pancreatitis (AP) that is characterized by inflammatory up-regulation. Nitric oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) regulate vascular function and mitigate inflammation. To investigate the influence of NO-NSAIDs on AP. AP was induced by the biliopancreatic duct outlet exclusion-closed duodenal loops model. Treatment with NO-flurbiprofen, NO-ibuprofen, NO-aspirin, or their parental drugs was done (i) 1 h before, (ii) 1 h after, (iii) 1 h before and 4 h after, or (iv) 4 h after surgery. The degree of severity was evaluated using biochemical and histopathological analyses. NO-NSAIDs given before and during the first hour of the noxia decreased blood levels of amylase, lipase, C-reactive protein, IL-6, IL-10, heat shock protein 72, prostaglandin E2 inactive metabolite, and 8-isoprostane, as well as pancreatic and lung myeloperoxidase and cyclooxygenase. Acinar and fat necrosis, hemorrhage, and leukocyte infiltrate were also reduced. The best protection was achieved when treatment was performed 1 h before and 4 h after triggering AP. NO-flurbiprofen was the most effective drug. AP severity was significantly a...Continue Reading

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Citations

Jul 23, 2011·Antioxidants & Redox Signaling·Péter Hegyi, Zoltán Rakonczay
Jun 7, 2008·The Journal of Clinical Investigation·Laura I Cosen-BinkerHerbert Y Gaisano
Mar 7, 2014·PloS One·Jordan M Willcox, Alastair J S Summerlee
Nov 26, 2010·World Journal of Gastroenterology : WJG·Marcelo-G BinkerLaura-I Cosen-Binker
Jun 24, 2008·Experimental Physiology·Marcelo G BinkerLaura I Cosen-Binker
Aug 8, 2008·Basic & Clinical Pharmacology & Toxicology·Riku KorhonenEeva Moilanen
Mar 10, 2010·Pharmaceuticals·Raffaele PezzilliRoberto Corinaldesi
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Nov 29, 2017·Annals of the Royal College of Surgeons of England·K A BaxterZzr Hamady
Jul 18, 2018·European Journal of Pharmacology·Paolo FagoneFerdinando Nicoletti

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