Phenidone attenuates oxygen/glucose deprivation-induced neurotoxicity by antioxidant and antiapoptotic action in mouse cortical cultures.

M B Wie, Y J Cho, W K Jhoo, H C Kim

Index: Neurosci. Lett. 272(2) , 91-4, (1999)

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Abstract

The abrupt elevation in the levels of cyclooxygenase or lipoxygenase metabolites of arachidonic acid during cerebral ischemia contributes to neuronal injury. Recently, evidence has accumulated that both excitotoxic and apoptotic features can coexist in ischemia models in vitro and in vivo. In this study, we evaluated whether phenidone, an inhibitor of both cyclooxygenase and lipoxygenase, can provide protection against excitotoxin- or ischemia-induced neurotoxicity, including the staurosporine apoptosis model, in mouse cortical cultures. We examined the protective effect of phenidone against free radical injuries induced by arachidonic acid, hydrogen peroxide, xanthine/xanthine oxidase, Fe2+/ascorbic acid. Pre- and post-treatment with phenidone (300 microM for 24 h) moderately attenuated the neuronal injury induced by 50 microM kainate and oxygen/glucose deprivation (45 min) by 33% and 50%, respectively. It had no effect on NMDA induced injury (150 microM for 5 min). The maximum dose of phenidone (300 microM) reduced the oxidative injury induced by arachidonic acid (71% inhibition), hydrogen peroxide (95% inhibition), xanthine/xanthine oxidase (57% inhibition), and Fe2+/ascorbic acid (99% inhibition) neurotoxicity. Phenidone (300 microM) decreased staurosporine (100 nM)-induced apoptosis to 30%. These results suggest that phenidone may contribute to neuronal survival by modulating oxidative stress, which is involved in the excitotoxic and apoptotic processes occurring under ischemic conditions.