Abstract
Retinal pigment epithelial (RPE) cells maintain homeostasis at the retina and they are under continuous oxidative stress. Cigarette smoke is a prominent environmental risk factor for age-related macular degeneration (AMD), which further increases the oxidant load in retinal tissues. In this study, we measured oxidative stress and inflammatory markers upon cigarette smoke-derived hydroquinone exposure on human ARPE-19 cells. In addition, we studied the effects of commercial Resvega product on hydroquinone-induced oxidative stress. Previously, it was observed that Resvega induces autophagy during impaired protein clearance in ARPE-19 cells, for which it has the potential to alleviate pro-inflammatory pathways. Cell viability was determined while using the lactate dehydrogenase (LDH) and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and the cytokine levels were measured using the enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) production were measured using the 2′,7′-dichlorofluorescin diacetate (H2DCFDA) probe. Hydroquinone compromised the cell viability and increased ROS production in ARPE-19 cells. Resvega significantly improved cell viability upon hydroquinone exposure and reduced the release of interleukin (IL)-8 and monocytic chemoattractant protein (MCP)-1 from RPE cells. Resvega, N-acetyl-cysteine (NAC) and aminopyrrolidine-2,4-dicarboxylic acid (APDC) alleviated hydroquinone-induced ROS production in RPE cells. Collectively, our results indicate that hydroquinone induces cytotoxicity and increases oxidative stress through NADPH oxidase activity in RPE cells, and resveratrol-containing Resvega products prevent those adverse effects.
Highlights
The prevalence of degenerative diseases, such as age-related macular degeneration (AMD), increases along with the extension of human life expectancies [1,2]
Retinal pigment epithelium (RPE) cells are primarily degenerated during the pathogenesis of AMD, which subsequently results in functional disruption and eventually the death of photoreceptors [3,4,5]
Hydroquinone induces the formation of membrane blebs, which promotes the development of drusen and induces actin protein rearrangement to globular aggregates in RPE cells [18,19,20]
Summary
The prevalence of degenerative diseases, such as age-related macular degeneration (AMD), increases along with the extension of human life expectancies [1,2]. Cigarette smoke is one of the most important environmental risk factors of AMD, and it is known to damage RPE cells [6]. It promotes the formation of 4-hydroxynonenal (4-HNE), the end product of lipid peroxidation that activates Nucleotide-binding domain, Leucine-rich repeat, and Pyrin domain 3 (NLRP3) inflammasome in RPE cells [6,7]. Hydroquinone is cytotoxic, immunotoxic, and carcinogenic, as well as immunosuppressive upon prolonged exposure [5,12] It increases apoptosis, damages cellular macromolecules, activates cell signaling pathways, such as caspases, and it can be unfavorable for redox-sensitive molecules, such as nuclear factor kappa B (NF-κB) [5,6,11,12,13,14,15]. Smokers have increased hydroquinone plasma levels, and hydroquinone probably reaches RPE cells through circulation [21]
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