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Toxicology ; 214(1-2): 131-9, 2005 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-16085349

RESUMEN

We investigated the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the levels of plasma and brain matrix metalloproteinase-9 (MMP-9) and the expression of nuclear factor kappa B (NF-kappaB) during experimental focal cerebral ischemia. The 3-aminobenzamide (3-AB), a PARP inhibitor, and saline were administered to 80 Sprague-Dawley rats [3-AB group; 5 rats for plasma sampling, 35 for brain sampling, and 40 for TTC staining] and to 85 rats (10, 35, and 40, respectively), respectively, 10 min before the occlusion of the left middle cerebral artery (MCAo) for 2 h. Infarct volume was measured by TTC staining, the serial levels of plasma and brain MMP-9 were measured by zymography just before and 2, 4, 8, 24, 48, and 72 h after MCAo, brain NF-kappaB activity was determined by Western blotting, and neutrophil infiltration was evaluated by assessing myeloperoxidase activity. Compared with control group, the levels of plasma and brain MMP-9, brain NF-kappaB, and MPO activities were significantly reduced in 3-AB group at each time point (p<0.05). Plasma MMP-9 increased maximally at 4h and then decreased rapidly, brain MMP-9 increased maximally at 24 h and persisted until 72 h, and NF-kappaB increased maximally at 24h and then decreased slowly in both groups. Therefore, the PARP inhibitor reduces the expression of MMP-9 and NF-kappaB and the infiltration of neutrophils in ischemic stroke.


Asunto(s)
Benzamidas/uso terapéutico , Isquemia Encefálica/complicaciones , Encéfalo/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/sangre , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Benzamidas/farmacología , Encéfalo/enzimología , Encéfalo/metabolismo , Isquemia Encefálica/enzimología , Modelos Animales de Enfermedad , Metaloproteinasa 9 de la Matriz/biosíntesis , FN-kappa B/biosíntesis , Ratas , Ratas Sprague-Dawley , Accidente Cerebrovascular/enzimología , Accidente Cerebrovascular/etiología , Regulación hacia Arriba
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