Bisphenol A induced apoptosis via oxidative stress generation involved Nrf2/HO‐1 pathway and mitochondrial dependent pathways in human retinal pigment epithelium (ARPE‐19) cells

Abstract

Bisphenol A (BPA) is an estrogen‐like compound, and an environmental hormone, that is commonly used in daily life. Therefore, it may enter the human body through food or direct contact, causing BPA residues in blood and urine. Because most studies focused on the analysis of BPA in reproductive cells or tissues, regarding evidence the effect of BPA on human retinal pigment epithelium (ARPE‐19) cells unavailable. Accordingly, the present study explored the cytotoxicity of BPA on ARPE‐19 cells. After BPA treatment, the expression of Bcl‐XL an antiapoptotic protein, in the mitochondria decreased, and the expression of Bax, a proapoptotic protein increased. Then the mitochondrial membrane potential was affected. BPA changed in mitochondrial membrane potential led to the release of cytochrome C, which activated caspase‐9 to promote downstream caspase‐3 leading to cytotoxicity. The nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and heme oxygenase 1 (HO‐1) pathway play a major role in age‐related macular degeneration. Our results showed that expression of HO‐1 and Nrf2 suppressed by BPA. Superoxide dismutase and catalase, which Nrf2 downstream antioxidants, were degraded by BPA. AMP‐activated kinase (AMPK), which can regulate the phosphorylation of Nrf2, and the phosphorylation of AMPK expression was reduced by BPA. Finally, BPA‐induced ROS generation and cytotoxicity were reduced by N‐acetyl‐l‐cysteine. Taken together, these results suggest that BPA induced ARPE‐19 cells via oxidative stress, which was associated with down regulated Nrf2/HO‐1 pathway, and the mitochondria dependent apoptotic signaling pathway.

Nattokinase attenuates bisphenol A or gamma irradiation-mediated hepatic and neural toxicity by activation of Nrf2 and suppression of inflammatory mediators in rats

“…Based on the aforementioned data, our results revealed that BPA or γ-irradiation concomitant with oxidative stress and neuroinflammation, there is a remarkable suppression in the gene expression of both Nrf2 and HO-1. These results work in with that of Chiang et al ( 2022 ) who observed downregulation of the Nrf2 and HO-1 gene transcription upon intoxication with BPA. Moreover, Zhang et al ( 2021 ) demonstrated that irradiation impedes the protein and gene expression of the Nrf2 and HO-1 via ROS the main mediators of radiation-induced damage, therefore, inducing cell apoptosis and stimulating numerous inflammatory factors.…”

Protective Effect of Rutin on Triethylene Glycol Dimethacrylate-Induced Toxicity through the Inhibition of Caspase Activation and Reactive Oxygen Species Generation in Macrophages

“…Macrophages play a crucial role in the immune system response against toxins and invasive pathogens, such as viruses, microbes, and toxics [ 24 , 25 , 26 ]. Overactivation of macrophages in the human body leads to the production of proinflammatory and lethal mediators, including cytokines, proteases, free radicals, and ROS [ 27 ].…”

Protective effect of wogonin on inflammatory responses in BisGMA‐treated macrophages through the inhibition of MAPK and NFκB pathways

“…The protein related densities were measured and quantified by Infinity CX5 detection system (Vilber Lourmat, France). 22,23…”