TY - JOUR
T1 - Olprinone, a PDE3 inhibitor, modulates the inflammation associated with myocardial ischemia-reperfusion injury in rats
AU - Di Paola, Rosanna
AU - Mazzon, Emanuela
AU - Paterniti, Irene
AU - Impellizzeri, Daniela
AU - Bramanti, Placido
AU - Cuzzocrea, Salvatore
PY - 2011/1/15
Y1 - 2011/1/15
N2 - Coronary ischemia and subsequent reperfusion result in deleterious effects, one of the principal ones being vascular and myocardial inflammation. Olprinone hydrochloride, a specific phosphodiesterase III inhibitor, has anti-inflammatory effects in addition to its inotropic and vasodilator effects. The purpose of this study was to examine the beneficial effects of olprinone on myocardial ischemia-reperfusion injury. Myocardial ischemia-reperfusion injury was caused by clamping the LAD (left anterior descending) coronary artery for 25 min followed by a release of the clamp allowing reperfusion for 1 h. Olprinone i.p. (0.2 mg/kg, i.p.) was administrated 15 min after ischemia. The olprinone administration significantly reduced the: (1) histological evidence of myocardial injury, (2) pro-inflammatory cytokines: tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β), (3) adhesion molecules: Inter-Cellular Adhesion Molecule 1 (ICAM-1) and P-Selectin, (4) nitrotyrosine formation, (5) nuclear factor kappa-B (NF-κB) expression, (6) Poly (ADP-ribose) (PAR) formation, and (7) apoptosis (Bax, Bcl-2, Fas-L and terminal deoxynucleotidyl transferase-mediated UTP end labeling (TUNEL). Based on these findings this study provides the evidence that treatment with olprinone ameliorated the inflammatory process associated with myocardial ischemia-reperfusion in rats and suggests that this drug may have potential in the treatment of various ischemia and reperfusion diseases.
AB - Coronary ischemia and subsequent reperfusion result in deleterious effects, one of the principal ones being vascular and myocardial inflammation. Olprinone hydrochloride, a specific phosphodiesterase III inhibitor, has anti-inflammatory effects in addition to its inotropic and vasodilator effects. The purpose of this study was to examine the beneficial effects of olprinone on myocardial ischemia-reperfusion injury. Myocardial ischemia-reperfusion injury was caused by clamping the LAD (left anterior descending) coronary artery for 25 min followed by a release of the clamp allowing reperfusion for 1 h. Olprinone i.p. (0.2 mg/kg, i.p.) was administrated 15 min after ischemia. The olprinone administration significantly reduced the: (1) histological evidence of myocardial injury, (2) pro-inflammatory cytokines: tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β), (3) adhesion molecules: Inter-Cellular Adhesion Molecule 1 (ICAM-1) and P-Selectin, (4) nitrotyrosine formation, (5) nuclear factor kappa-B (NF-κB) expression, (6) Poly (ADP-ribose) (PAR) formation, and (7) apoptosis (Bax, Bcl-2, Fas-L and terminal deoxynucleotidyl transferase-mediated UTP end labeling (TUNEL). Based on these findings this study provides the evidence that treatment with olprinone ameliorated the inflammatory process associated with myocardial ischemia-reperfusion in rats and suggests that this drug may have potential in the treatment of various ischemia and reperfusion diseases.
KW - Apoptosis
KW - Inflammation
KW - Myocardial ischemia-reperfusion
KW - Olprinone
KW - Phosphodiesterase III inhibitor
KW - Pro-inflammatory cytokine
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U2 - 10.1016/j.ejphar.2010.10.043
DO - 10.1016/j.ejphar.2010.10.043
M3 - Article
C2 - 21035441
AN - SCOPUS:78651103004
VL - 650
SP - 612
EP - 620
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2-3
ER -