title: Beneficial synergistic effects of concurrent treatment with cilostazol and probucol against focal cerebral ischemic injury in rats.
abstract: In the present study, we assessed the beneficial synergistic effects of concurrent treatment with low doses of cilostazol and probucol against focal cerebral ischemic infarct in rats. The ischemic infarct induced by 2-h occlusion of middle cerebral artery (MCA) and 22-h reperfusion was significantly reduced in rat brain that received cilostazol (20 mg/kg) and probucol (30 mg/kg) twice together with prominent improvement of neurological function compared to the effect of cilostazol or probucol monotherapy. Increased myeloperoxidase activity, a marker of neutrophil infiltration, observed in the penumbral zone of vehicle-treated brain was more significantly reduced by cilostazol plus probucol in combination. Increased superoxide-, nitrotyrosine (a marker of peroxynitrite)-, poly(ADP-ribose) [a marker for poly(ADP-ribose) polymerase activity]-, and cleaved caspase-3-positive cells (a proapoptotic marker) in the vehicle sample were significantly attenuated by the combination therapy, while individual treatment with low dose of cilostazol or probucol showed a marginal effect. Taken together, it is suggested that the neuroprotective potentials of combination therapy with low doses of cilostazol plus probucol may provide beneficial therapeutic intervention in reducing the focal cerebral ischemic infarct in rats.
authors.affiliation: Department of Pharmacology, College of Medicine, Pusan National University, Busan 602-739, Republic of Korea.
authors.forename: So Youn
authors.initials: SY
authors.lastname: Park
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Chi Dae
authors.initials: CD
authors.lastname: Kim
authors.forename: Byung Yong
authors.initials: BY
authors.lastname: Rhim
authors.forename: Ki Whan
authors.initials: KW
authors.lastname: Hong
authors.forename: Won Suk
authors.initials: WS
authors.lastname: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D000077407:Cilostazol; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000378:metabolism; D011341:Probucol / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D013687:Telencephalon / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D004338:Drug Combinations; D018696:Neuroprotective Agents; D013777:Tetrazoles; D013481:Superoxides; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D000077407:Cilostazol; D011341:Probucol