Carvedilol activates nuclear factor E2-related factor 2/ antioxidant response element pathway to inhibit oxidative stress and apoptosis of retinal pigment epithelial cells induced by high glucose

Abstract

Diabetic retinopathy (DR) is the most prominent manifestation of diabetic microangiopathy and is a serious complication of diabetes. Despite extensive researches focusing on DR, treatment options for DR are still limited. Carvedilol (CAR) has vasodilatory, antioxidant stress and anti-inflammatory effects and poses a vital role in addressing the issue of diabetic complications. This paper attempts to explore this property of CAR and investigate into its effects on DR. First, ARPE-19 cells were treated with different concentrations of CAR and cells were induced with 30 mM high glucose (HG) to establish a DR cell model. Cell viability was assayed by cell counting kit-8 (CCK-8) with or without HG induction. Cellular inflammation and oxidative stress were evaluated by enzyme-linked immunosorbent assay (ELISA) and corresponding kits. The measurement of apoptosis levels was conducted by Terminal dUTP nick-end labeling (TUNEL) and Western blotting. The protein levels related to Nrf2/ARE signaling pathway were assessed by Western blotting. Finally, cellular inflammation, oxidative stress and apoptosis in ARPE-19 cells pretreated with Nrf2 inhibitor ML385 were tested again by the same methods. Results showed that under HG induction, CAR effectively improved ARPE-19 cell viability, inhibited cellular inflammation, oxidative stress, and apoptosis. Moreover, CAR activated Nrf2/ARE signaling pathway, which further suppressed cellular inflammation, oxidative stress, and apoptosis. Overall, CAR inhibited HG-induced oxidative stress and apoptosis in retinal pigment epithelial cells by activating Nrf2/ARE pathway.

Recombinant human klotho protects against hydrogen peroxide-mediated injury in human retinal pigment epithelial cells via the PI3K/Akt-Nrf2/HO-1 signaling pathway

“…Unfortunately, there is no corresponding H 2 O 2 group (500 μm) in our experiment to verify this conjecture. Nrf2/HO-1 is an antioxidant defense pathway that plays a major role in protecting RPE cells against oxidative damages [ 44 , 45 ]. Mice models revealed that under-expression of Nrf2 can lead to AMD-like pathological changes in the eye [ 46 ].…”

Platycodin D inhibits diabetic retinopathy via suppressing TLR4/MyD88/NF‐κB signaling pathway and activating Nrf2/HO‐1 signaling pathway

“…There is growing evidence pointing to the RPE essential propriety and its impairment in DR (Ponnalagu et al., 2017). HG results in oxidative stress and inflammation, as well as induces apoptosis in ARPE‐19 cells (Li & Xiao, 2021; Shi et al., 2020; Zhang et al., 2022). Similar findings were observed in our study as well, where both ROS, TNF‐α, IL‐1β, and IL‐6 levels and cell apoptosis increased in HG treatment group.…”

Deletion of Nrf2 induced severe oxidative stress and apoptosis in mice model of diabetic bladder dysfunction

“…Several studies already clari ed that oxidative stress induced apoptosis in different cell models or animal models [8][9][10] .Here some classic molecules were tested to identify the effect of Nrf2 deletion on the apoptosis pathway in type 2 diabetes mice. There was an increase of the expression level of caspase 3, an apoptosis-related molecule, in the bladder tissues of KO group compared with WT group (Fig.…”