Inducible nitric oxide synthase-deficient mice exhibit resistance to the acute pancreatitis induced by cerulein

Salvatore Cuzzocrea, Emanuela Mazzon, Laura Dugo, Ivana Serraino, Tommaso Centorrino, Antonio Ciccolo, F. A J Van De Loo, Domenico Britti, Achille P. Caputi, Christoph Thiemermann

Research output: Contribution to journalArticle

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Abstract

Oxidative stress plays an important role in the early stage of acute pancreatitis as well as the associated multiple organ injury. Here we compare the degree of pancreatitis caused by cerulein in mice lacking the inducible (or type 2) nitric oxide synthase (iNOS) and in the corresponding wild-type mice. Intraperitoneal injection of cerulein resulted in wild-type mice in a severe, acute pancreatitis, which was characterized by edema, neutrophil infiltration, tissue hemorrhage and cell necrosis as well as increases in the serum levels of amylase and/or lipase. The infiltration of the pancreatic tissue of these animals with neutrophils (measured as increase in myeloperoxidase activity) was associated with up-regulation/expression of the adhesion molecules ICAM-1 and P-selectin as well as signs of enhanced lipid peroxidation (e.g., increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in the staining (immunoreactivity) for nitrotyrosine and poly (ADP-ribose) synthetase (PARS) in the pancreas of cerulein-treated iNOS wild-type mice. In contrast, the degree of pancreatic inflammation and tissue injury (histological score), upregulation/ expression of P-selectin and ICAM-1, the staining for nitrotyrosine and PARS, and lipid peroxidation was markedly reduced in pancreatic tissue sections obtained from cerulein-treated iNOS-deficient mice. These findings support the view that iNOS plays an important, pro-inflammatory role in the acute pancreatitis caused by cerulein in mice.

Original languageEnglish
Pages (from-to)416-422
Number of pages7
JournalShock
Volume17
Issue number5
Publication statusPublished - May 2002

Fingerprint

Ceruletide
Nitric Oxide Synthase Type II
Pancreatitis
Poly Adenosine Diphosphate Ribose
P-Selectin
Intercellular Adhesion Molecule-1
Ligases
Lipid Peroxidation
Up-Regulation
Staining and Labeling
Neutrophil Infiltration
Multiple Trauma
Amylases
Intraperitoneal Injections
Malondialdehyde
Lipase
Peroxidase
Pancreas
Edema
Oxidative Stress

Keywords

  • Free radicals
  • Inflammation
  • iNOS
  • Peroxynitrite
  • Poly (ADP-ribose) polymerase

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

Cuzzocrea, S., Mazzon, E., Dugo, L., Serraino, I., Centorrino, T., Ciccolo, A., ... Thiemermann, C. (2002). Inducible nitric oxide synthase-deficient mice exhibit resistance to the acute pancreatitis induced by cerulein. Shock, 17(5), 416-422.

Inducible nitric oxide synthase-deficient mice exhibit resistance to the acute pancreatitis induced by cerulein. / Cuzzocrea, Salvatore; Mazzon, Emanuela; Dugo, Laura; Serraino, Ivana; Centorrino, Tommaso; Ciccolo, Antonio; Van De Loo, F. A J; Britti, Domenico; Caputi, Achille P.; Thiemermann, Christoph.

In: Shock, Vol. 17, No. 5, 05.2002, p. 416-422.

Research output: Contribution to journalArticle

Cuzzocrea, S, Mazzon, E, Dugo, L, Serraino, I, Centorrino, T, Ciccolo, A, Van De Loo, FAJ, Britti, D, Caputi, AP & Thiemermann, C 2002, 'Inducible nitric oxide synthase-deficient mice exhibit resistance to the acute pancreatitis induced by cerulein', Shock, vol. 17, no. 5, pp. 416-422.
Cuzzocrea S, Mazzon E, Dugo L, Serraino I, Centorrino T, Ciccolo A et al. Inducible nitric oxide synthase-deficient mice exhibit resistance to the acute pancreatitis induced by cerulein. Shock. 2002 May;17(5):416-422.
Cuzzocrea, Salvatore ; Mazzon, Emanuela ; Dugo, Laura ; Serraino, Ivana ; Centorrino, Tommaso ; Ciccolo, Antonio ; Van De Loo, F. A J ; Britti, Domenico ; Caputi, Achille P. ; Thiemermann, Christoph. / Inducible nitric oxide synthase-deficient mice exhibit resistance to the acute pancreatitis induced by cerulein. In: Shock. 2002 ; Vol. 17, No. 5. pp. 416-422.
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