Edaravone protects PC12 cells from ischemic-like injury via attenuating the damage to mitochondria

Abstract

Background: Edaravone had been validated to effectively protect against ischemic injuries. In this study, we investigated the protective effect of edaravone by observing the effects on anti-apoptosis, regulation of Bcl-2/Bax protein expression and recovering from damage to mitochondria after OGD (oxygen-glucose deprivation)-reperfusion. Methods: Viability of PC12 cells which were injured at different time of OGD injury, was quantified by measuring MTT (2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) staining. In addition, PC12 cells' viability was also quantified after their preincubation in different concentration of edaravone for 30 min followed by (OGD). Furthermore, apoptotic population of PC12 cells that reinsulted from OGD-reperfusion with or without preincubation with edaravone was determined by flow cytometer analysis, electron microscope and Hoechst/PI staining. Finally, change of Bcl-2/Bax protein expression was detected by Western blot. Results: (1) The viability of PC12 cells decreased with time (1~12 h) after OGD. We regarded the model of OGD 2 h, then replacing DMEM (Dulbecco's Modified Eagle's Medium) for another 24 h as an OGD-reperfusion in this research. Furthermore, most PC12 cells were in the state of apoptosis after OGD-reperfusion. (2) The viability of PC12 cells preincubated with edaravone at high concentrations (1, 0.1, 0.01 µmol/L) increased significantly with edaravone protecting PC12 cells from apoptosis after OGD-reperfusion injury. (3) Furthermore, edaravone attenuates the damage of OGD-reperfusion on mitochondria and regulated Bcl-2/Bax protein imbalance expression after OGD-reperfusion. Conclusion: Neuroprotective effects of edaravone on ischemic or other brain injuries may be partly mediated through inhibition of Bcl-2/Bax apoptotic pathways by recovering from the damage of mitochondria.

Protective Effects of Edaravone against Methamphetamine-Induced cardiotoxicity

“…ED decreased METH induced ROS production and also significant decreased in LPO and PC content compared with METH treated group. Our data was consistent with previous studies that reported antioxidant and radical scavenging effects of ED (35,36). High level of ROS in cell can damage cell and organelle membrane such as mitochondrial membrane which could triggering cell death signaling that finally could lead to several pathological conditions such as myocardial infarction (37,38).…”

Protective effects of the free radical scavenger edaravone against glutamate neurotoxicity in nearly pure neuronal culture

“…It has been suggested that the mechanisms of the protective effect involve inhibition of the activation of microglia [10,11] and astrocytes [10], and protection against endothelial cell injury [12], as well as the inhibition of cerebral edema [13]. Regarding the effect on the neurons themselves, it has been reported that cultured hippocampal neurons and neuronal PC 12 cells treated with edaravone were protected against glucose-oxygen deprivation [14,15]. However, as far as we know, there have been no reports about the effect of edaravone on neurons themselves against glutamate neurotoxicity, i. e., excitotoxicity.…”

Upregulation of 20-HETE Synthetic Cytochrome P450 Isoforms by Oxygen–Glucose Deprivation in Cortical Neurons

“…On the other hand, ROS is an important cause of cell death. Studies have indicated that many free radical scavengers attenuate cell death after OGD (Zhang et al 2008; Song et al 2006; Wu et al 2006). Direct 20-5,14–HEDGE-induced ROS generation and HET0016-attenuated ROS production after OGD in cultured neurons, and the similar neuroprotection provided by HET0016 and 20-HETE antagonist 20-6,15–HEDGE support the view that 20-HETE contributes to the adverse effects after OGD.…”