The antioxidant effects of riluzole on the APRE-19 cell model injury-induced by t-BHP

Abstract

BackgroundAge-related macular degeneration (AMD) causes the dysfunction of the retinal pigment epithelial (RPE) cells. In this study, we examined the effects of riluzole, a sustained activator of the TRAAK potassium channel, on human RPE (ARPE-19) cells in an oxidant-induced cell-injury model and elucidate the mechanism of riluzole on RPE cell apoptosis.MethodsThe follow four groups of ARPE-19 cells were treated with riluzole and/or tert-butyl hydroperoxide (t-BHP) for 24.0 h: control, t-BHP, riluzole, and t-BHP + riluzole. Cell apoptosis was measured by flow cytometry, and Western blotting was performed to analyze the expression of the weakly inward rectifying potassium (TRAAK) channel. Finally, the mitochondrial membrane potential (Δψm) was detected by flow cytometry, and cytochrome C (Cyt-c) release was assessed by Western blotting.ResultsThe viability of the cells in the cotreated group was significantly higher (85.6 ± 3.1%) than that in the t-BHP group (66.2 ± 2.5%). In addition, the cells in the cotreated group had a higher effect on increasing the expression of TRAAK than the t-BHP group. The results also showed that Cyt-c translocation significantly decreased and Δψm increased in the cotreated group.ConclusionsThese results demonstrate that riluzole protects RPE cells from apoptosis. The protection mechanism of riluzole could be from stabilizing mitochondrial Δψm and preventing the release of Cyt-c. Changes in TRAAK expression might also contribute to the protection of RPE cells.

The Impact of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis

“…Riluzole, an anti-glutamatergic drug approved by the U.S. Food and Drug Administration in 1995, can delay the progression of the disease and the lifespan of patients to a certain extent, but its efficacy is limited [80]. Studies have reported that riluzole can inhibit glutamate release and glutamatergic transmission in the brain and can attenuate oxidative damage in neuronal cells caused by ALS in SOD1-G93A mice [81,82]. In addition, riluzole has also been reported to increase survival in ALS patients who have undergone a tracheostomy [83].…”

Potassium bromate-induced cell model of age-related macular degeneration in vitro

“…Treatment with at higher concentrations (30 µM) causes cytotoxicity and ROS formation effect in cells compared with that in KBrO 3 (25 µM) (34). In addition, t-BHP has been reported to induce cell apoptosis at doses >250 µM (14). In RPE cells, exposure to 1 mM H 2 O 2 for 24 h markedly inhibited viability compared with the control group (12,13).…”

“…Hydrogen peroxide (H 2 O 2 ) is widely utilized to induce oxidative stress in human RPE cells (12), displaying dose-and time-dependent effects (12,13). Chemical oxidants, including tert-butyl hydroperoxide (t-BHP) (14) and bisphenol A (15), are also used to induce oxidative stress in vitro. Additionally, acrolein-induced reactive oxygen species (ROS) overproduction has been employed for the induction of oxidative stress (16).…”

Oxidative Stress as a Therapeutic Target in Amyotrophic Lateral Sclerosis: Opportunities and Limitations

“…Further, they also reported that riluzole has antioxidant properties in other disease models. Riluzole decreased cell death against tert-butyl hydroperoxide (t-BHP)-treated human retinal pigment epithelial cells [ 60 ]. Riluzole has neuroprotective effects on Alzheimer’s disease in rat models, due to decreased acetylcholinesterase (AChE) activity and oxidative stress marker [ 61 ].…”