Therapeutic effects and mechanisms of action of mannitol during H2O2-induced oxidative stress in human retinal pigment epithelium cells.
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
H(2)O(2) dose-dependently reduced the cell viability of hRPE cells. This negative effect was significantly counteracted by pretreatment with mannitol (1 mM). H(2)O(2) significantly stimulated the formation of OFR and LP. These increases were dose-dependently and significantly blunted by mannitol. Furthermore, treatment with H(2)O(2) 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 H(2)O(2)-induced oxidative stress by increasing the level of catalase, but not the level of MnSOD.


CONCLUSIONS
This study supports an antioxidative role for mannitol that acts through up-regulating the level of catalase, which is decreased by H(2)O(2).
Liu
Jorn-Hon
JH
Department of Ophthalmology, Cheng Hsin General Hospital, Taipei, Taiwan, Republic of China.
Chen
Mi-Mi
MM
Huang
Jhao-Wei
JW
Wann
Hsiung
H
Ho
Li-Kang
LK
Pan
Wynn H T
WH
Chen
Yei-Ching
YC
Liu
Chi-Ming
CM
Yeh
Ming-Yang
MY
Tsai
Shen-Kou
SK
Young
Mason Shing
MS
Ho
Low-Tone
LT
Kuo
Cheng-Deng
CD
Chuang
Hui-Yen
HY
Chao
Fang-Ping
FP
Chao
Hsiao-Ming
HM
D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000008:administration & dosage / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008353:Mannitol / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D008353:Mannitol; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase