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EUK 134, a synthetic superoxide dismutase (SOD)/catalase mimetic, has exhibited potent antioxidant activities and inhibited the formation of β-amyloid and related amyloid fibril.

In vitro:EUK-134, a salen-manganese complex, showed potent catalase and cytoprotective activities and SOD activity. After middle cerebral artery occlusion, EUK-134 administration at 3 hr significantly reduced brain infarct size, with the highest dose apparently preventing further infarct growth[1]. Administration of EUK 134 (20 μM) prevented Aβ-induced microglial proliferation in vitro[2]. In human neuroblastoma cell line SK-N-MC, pre-treatments with EUK134 protected cells against H2O2-induced oxidative stress through inhibition of MAPK pathway in a dose-dependent manner.EUK134 also decreased the expression of pro-apoptotic genes p53 and Bax and enhanced expression of anti-apoptotic Bcl-2 gene [3]. Incubation of human amylin with EUK-134 significantly inhibited amyloid formation at two molar ratios of 1:1 and 5:1 (drugs to protein)[4].

In vivo:Compared to the vehicle-injected rats, the EUK-134-treated group at doses of 0.5 and 5.0 μmol/kg (0.25 and 2.5 mg/kg, respectively) exhibited infarct volumes that were significantly lower than those of vehicle-injected rats. At 5.0 μmol/kg, EUK-134 reduced the infarct volume by 90% when compared with that of the vehicle controls [1].EUK-134 protected most of the vulnerable neurons from excitotoxic cell death.EUK-134 significantly reduced (P< 0.05) KA-induced neuronal damage in CA1 (22% of total neurons), an almost complete protection in CA3 (7%) and piriform cortex (14%), indicating that EUK-134 prevented most but not all neuronal damage resulting from KA-induced seizure activity [5].

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