Dipyrone inhibits neuronal cell death and diminishes hypoxic/ischemic brain injury.
Neurosurgery
; 69(4): 942-56, 2011 Oct.
Article
en En
| MEDLINE
| ID: mdl-21552169
BACKGROUND: Dipyrone is an analgesic and antipyretic drug usually prescribed for patients with inflammatory conditions. We recently identified dipyrone as an antiapoptotic agent by screening a library of 1040 compounds for their ability to inhibit cytochrome c release from isolated mitochondria. OBJECTIVE: We investigated the potential neuroprotective properties of dipyrone in cerebral ischemia. METHODS: We evaluated the protective effects of dipyrone in experimental models of neuronal hypoxia/ischemia, including an oxygen/glucose deprivation model in primary cerebrocortical neurons and a focal cerebral ischemia model in mice. RESULTS: Dipyrone reduced hypoxia/ischemia injury in both cellular and animal models. Dipyrone inhibited the release of cytochrome c and other mitochondrial apoptogenic factors from mitochondria into the cytoplasm, and attenuated subsequent caspase-9 and caspase-3 activation both in vitro and in vivo. Moreover, dipyrone prevented ischemia-induced changes in Bcl-2 and tBid, and ameliorated oxygen/glucose deprivation-mediated loss of mitochondrial membrane potential. Dipyrone also inhibited ischemia-induced reactive microgliosis. In the cellular models evaluated, dipyrone did not inhibit oxygen/glucose deprivation-induced cyclooxygenase-2 activation. CONCLUSION: Dipyrone is remarkably neuroprotective in cerebral ischemia, and its cyclooxygenase-independent protective properties are, at least in part, due to the inhibition of mitochondrial cell death cascades.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antiinflamatorios no Esteroideos
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Dipirona
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Apoptosis
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Fármacos Neuroprotectores
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Hipoxia-Isquemia Encefálica
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Neuronas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neurosurgery
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos