Protective Effects of a Lutein Ester Prodrug, Lutein Diglutaric Acid, against H₂O₂-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells

Muangnoi, Chawanphat, Phumsuay, Rianthong, Jongjitphisut, Nattapong, Waikasikorn, Pasin, Sangsawat, Monsin, Rashatasakhon, Paitoon, Paraoan, Luminita ORCID: 0000-0001-7568-7116 and Rojsitthisak, Pornchai (2021) Protective Effects of a Lutein Ester Prodrug, Lutein Diglutaric Acid, against H₂O₂-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (9). 4722-.

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Abstract

Oxidative stress-induced cell damage and death of the retinal pigmented epithelium (RPE), a polarized monolayer that maintains retinal health and homeostasis, lead to the development of age-related macular degeneration (AMD). Several studies show that the naturally occurring antioxidant Lutein (Lut) can protect RPE cells from oxidative stress. However, the poor solubility and low oral bioavailability limit the potential of Lut as a therapeutic agent. In this study, lutein diglutaric acid (Lut-DG), a prodrug of Lut, was synthesized and its ability to protect human ARPE-19 cells from oxidative stress was tested compared to Lut. Both Lut and Lut-DG significantly decreased H₂O₂-induced reactive oxygen species (ROS) production and protected RPE cells from oxidative stress-induced death. Moreover, the immunoblotting analysis indicated that both drugs exerted their protective effects by modulating phosphorylated MAPKs (p38, ERK1/2 and SAPK/JNK) and downstream molecules Bax, Bcl-2 and Cytochrome c. In addition, the enzymatic antioxidants glutathione peroxidase (GPx) and catalase (CAT) and non-enzymatic antioxidant glutathione (GSH) were enhanced in cells treated with Lut and Lut-DG. In all cases, Lut-DG was more effective than its parent drug against oxidative stress-induced damage to RPE cells. These findings highlight Lut-DG as a more potent compound than Lut with the protective effects against oxidative stress in RPE cells through the modulation of key MAPKs, apoptotic and antioxidant molecular pathways.

Item Type:	Article
Uncontrolled Keywords:	age-related macular degeneration, human retinal pigmented epithelium, oxidative stress, lutein, lutein diglutaric acid
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	10 May 2021 09:38
Last Modified:	09 Feb 2024 03:19
DOI:	10.3390/ijms22094722
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3121789