Protective effect of rutin against brain injury induced by acrylamide or gamma radiation: role of PI3K/AKT/GSK-3β/NRF-2 signalling pathway

Abstract

This study was designed to evaluate the effect of rutin on PI3K/AKT-signalling in case of acrylamide or γ-radiation-induced neurotoxicity. To induce brain damage, animals were received acrylamide (25 mg/kg b.wt./orally/day) or 5 Gy of γ-radiation exposure accompanied with an administration of rutin (200 mg/kg b.wt./orally/day). Our data revealed that, compared to acrylamide or γ-radiation, rutin activated PI3K/AKT/GSK-3β/NRF-2-pathway through increased protein levels of p-PI3K, p-AKT and p-GSK-3β and up-regulated the expression of NRF-2. This was achieved by modulating MDA, GST, IL-1β, IL-6 and reduced the interference of ROS with IGF-1 and NGF stimulating the PI3K/AKT-signaling. Furthermore, histopathological examinations of brain tissues showed that rutin has modulated tissue architecture after acrylamide or γ-radiation induced tissue damage. It could be concluded that rutin provides protection effect against acrylamide or γ-radiation-induced neurotoxicity via activation of the PI3K/AKT/GSK-3β/NRF-2-pathway by altering the phosphorylation state through its ability to scavenge free radicals generation, modulating gene expression and its anti-inflammatory effects.

Keywords: IL-1β; MDA; PI3K/AKT/GSK-3β/NRF-2; Rutin; acrylamide; γ-radiation.