Therapeutic Effects and Mechanisms of Action of Mannitol During H 2 O 2 -Induced Oxidative Stress in Human Retinal Pigment Epithelium Cells

Abstract

Background:

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. At a later stage, neovascular or exudative AMD can lead to severe central vision loss that is related to aging-associated cumulative oxidative stress of the human retinal pigment epithelium (hRPE) and choroid capillary. Early prevention with antioxidants is mandatory. The aim of this study was to determine whether and how mannitol can act as an antioxidant.

Methods:

The methods used included measurements of cell viability, oxygen free radical (OFR) levels, lipid peroxide (LP) levels, and OFR-related enzyme protein levels.

Results:

H₂O₂ dose-dependently reduced the cell viability of hRPE cells. This negative effect was significantly counteracted by pretreatment with mannitol (1 mM). H₂O₂ significantly stimulated the formation of OFR and LP. These increases were dose-dependently and significantly blunted by mannitol. Furthermore, treatment with H₂O₂ was associated with a reduction in the level of catalase, but not of manganese superoxide dismutase (MnSOD). In contrast, it was shown that mannitol protected hRPE cells against the H₂O₂-induced oxidative stress by increasing the level of catalase, but not the level of MnSOD.

Conclusion:

This study supports an antioxidative role for mannitol that acts through up-regulating the level of catalase, which is decreased by H₂O₂.

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