Influence of nitric oxide-donating nonsteroidal anti-inflammatory drugs on the evolution of acute pancreatitis.
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 ameliorated by NO-NSAIDs being the administration time essential to achieve optimal pancreatic protection that may result to be useful in the prevention of postendoscopic severe AP.
Cosen-Binker
Laura Iris
LI
Programa de Estudios Pancreáticos, Hospital de Clínicas, Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. laura.cosen.binker@utoronto.ca
Binker
Marcelo Gustavo
MG
Cosen
Rodica
R
Negri
Gustavo
G
Tiscornia
Osvaldo
O
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D004195:Disease Models, Animal; D018450:Disease Progression; D007263:Infusions, Parenteral; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D010183:Pancreatic Ducts / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020030:Nitric Oxide Donors