title: Neuroprotective effects of olprinone after cerebral ischemia/reperfusion injury in rats.
abstract: Olprinone hydrochloride, a specific phosphodiesterase III inhibitor, has anti-inflammatory effects in addition to its inotropic and vasodilatory effects. The purpose of this study was to examine the beneficial effects of olprinone on cerebral ischemia reperfusion injury. In the present study, we examined the detailed mechanisms underlying the inhibitory effects of olprinone on inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAo) in rats. Focal cerebral ischemia was induced by transient MCAo in the right hemisphere, via the external carotid artery into the internal carotid to block the origin of the median carotid artery. The rats were subjected to artery occlusion (2 h) followed by reperfusion (22 h). Olprinone was administered 5 min before reperfusion. MCAo-induced cerebral ischemia was associated with an increase in inducible nitric oxide synthase expression, nitrotyrosine formation, as well as IL-1β expression and ICAM-1 expression in ischemic regions. Olprinone treatment showed marked reduction in infarct size compared with control rats. These expressions were markedly inhibited by olprinone treatment. We also demonstrated that olprinone reduces levels of apoptosis (TUNEL, Bax and Bcl-2 expression) resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Based on these findings we propose that olprinone would be useful in lowering the risk of damage or improving function in ischemia-reperfusion brain injury-related disorders.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina 98100, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000818:Animals; D017209:Apoptosis; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D002540:Cerebral Cortex / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000523:psychology; D008297:Male; D018696:Neuroprotective Agents; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D007093:Imidazoles; D018696:Neuroprotective Agents; D010726:Phosphodiesterase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011728:Pyridones; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C059498:olprinone; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3