title: Olprinone, a specific phosphodiesterase (PDE)-III inhibitor, reduces the development of multiple organ dysfunction syndrome in mice.
abstract: Olprinone is a specific phosphodiesterase (PDE)-III inhibitor, which has been found to have anti-inflammatory effects in addition to its main inotropic and peripheral vasodilatory effects. In the present study we investigated the effects of olprinone (0.2mg/kg, i.p.) on the development of zymosan-induced multiple organ failure in mice. Treatment with olprinone attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan. Olprinone also attenuated the lung, liver and pancreatic injury, renal dysfunction as well as the increased lung and intestine myeloperoxidase (MPO) activity caused by zymosan. Immunohistochemical analysis for inducible nitric oxide synthase (iNOS), nitrotyrosine, poly(ADP-ribose) (PAR), tumor necrosis factor-α (TNF-α) and interleuchin-1β (IL-1β) revealed positive staining in pancreatic and intestinal tissue obtained from zymosan-injected mice. The degree of staining for nitrotyrosine, iNOS, PAR, TNF-α and IL-1β was markedly reduced in tissue sections obtained from zymosan-injected mice, which had received olprinone. In addition, administration of zymosan caused a severe illness in the mice characterized by significant loss of body weight and a 60% of mortality at the end of observation period (7 days). Treatment with olprinone significantly reduced the development of systemic toxicity, loss in body weight and mortality, caused by zymosan. This study provides evidence that olprinone attenuates the degree of zymosan-induced shock in mice.
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", S.S. 113 Via Palermo, CTR Casazza, Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000681:Amylases / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001202:Ascitic Fluid / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001219:Aspartate Aminotransferases / Q000097:blood; D001639:Bicarbonates / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001784:Blood Gas Analysis; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D003404:Creatinine / Q000097:blood; D053222:Fas Ligand Protein / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008049:Lipase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009102:Multiple Organ Failure / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009566:Nitrates / Q000097:blood / Q000378:metabolism; D009573:Nitrites / Q000097:blood / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058987:Phosphodiesterase 3 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D015054:Zymosan / Q000008:administration & dosage / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D001639:Bicarbonates; D053222:Fas Ligand Protein; C090509:Icam1 protein, mouse; D007093:Imidazoles; D053583:Interleukin-1beta; D009566:Nitrates; D009573:Nitrites; D019007:P-Selectin; D058987:Phosphodiesterase 3 Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011728:Pyridones; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D018799:Intercellular Adhesion Molecule-1; C002744:3-nitrotyrosine; D014443:Tyrosine; C059498:olprinone; D015054:Zymosan; D003404:Creatinine; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008049:Lipase; D000469:Alkaline Phosphatase; D000681:Amylases; D001663:Bilirubin