5-LOX Inhibitor Zileuton Reduces Inflammatory Reaction and Ischemic Brain Damage Through the Activation of PI3K/Akt Signaling Pathway.

5-LOX Inhibitor Zileuton Reduces Inflammatory Reaction and Ischemic Brain Damage Through the Activation of PI3K/Akt Signaling Pathway. Neurochem Res. 2016 Jul 5; Authors: Tu XK, Zhang HB, Shi SS, Liang RS, Wang CH, Chen CM, Yang WZ Abstract Previous studies from our laboratories showed that an anti-inflammatory drug, 5-lipoxygenase inhibitor zileuton, attenuates ischemic brain damage via inhibiting inflammatory reaction. However, it was elusive whether zileuton attenuates inflammatory reaction and ischemic brain damage through the modulation of PI3K/Akt signaling pathway. In the present study, we, for the first time, investigated whether PI3K/Akt pathway was involved in zileuton's anti-inflammatory and neuroprotective properties against brain damage following experimental ischemic stroke. Adult male Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO), then received treatment with zileuton or vehicle after the onset of ischemia. LY294002 was injected intracerebroventricularly to inhibit the activation of PI3K/Akt signaling pathway selectively. Neurological deficit scores, cerebral infarct volume, morphological characteristic and cerebral water content were assessed 24 h after cerebral ischemia. The enzymatic activity of myeloperoxidase (MPO) was measured 24 h after cerebral ischemia. Expression of p-Akt, t-Akt and COX-2 in ischemic brain were determined by western blot. NF-κB p65 immuno-positive cells in ischemic ...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research