title: Therapeutic effects and mechanisms of action of mannitol during H2O2-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
  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).
authors.affiliation: Department of Ophthalmology, Cheng Hsin General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Jorn-Hon
authors.initials: JH
authors.lastname: Liu
authors.forename: Mi-Mi
authors.initials: MM
authors.lastname: Chen
authors.forename: Jhao-Wei
authors.initials: JW
authors.lastname: Huang
authors.forename: Hsiung
authors.initials: H
authors.lastname: Wann
authors.forename: Li-Kang
authors.initials: LK
authors.lastname: Ho
authors.forename: Wynn H T
authors.initials: WH
authors.lastname: Pan
authors.forename: Yei-Ching
authors.initials: YC
authors.lastname: Chen
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Liu
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Yeh
authors.forename: Shen-Kou
authors.initials: SK
authors.lastname: Tsai
authors.forename: Mason Shing
authors.initials: MS
authors.lastname: Young
authors.forename: Low-Tone
authors.initials: LT
authors.lastname: Ho
authors.forename: Cheng-Deng
authors.initials: CD
authors.lastname: Kuo
authors.forename: Hui-Yen
authors.initials: HY
authors.lastname: Chuang
authors.forename: Fang-Ping
authors.initials: FP
authors.lastname: Chao
authors.forename: Hsiao-Ming
authors.initials: HM
authors.lastname: Chao
mesh_terms: 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
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D008353:Mannitol; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase