title: Amelioration of endotoxin-induced uveitis treated with the sea urchin pigment echinochrome in rats.
abstract: OBJECTIVE
  Echinochrome is a pigment present in the shells and spines of sea urchins. It has been reported to have several biologic protective effects, including in experimental models of myocardial ischemia/reperfusion injury, for which the proposed mechanisms are scavenging reactive oxygen species (ROS) and chelating iron. Endotoxin-induced uveitis (EIU) is an animal model of acute anterior segment intraocular inflammation that is induced by the injection of lipopolysaccharide (LPS). In this study, the therapeutic effect of echinochrome was examined in uveitis using the EIU model.
  
  
  METHODS
  EIU was induced in Lewis rats via 200 μg subcutaneous injections of LPS from Escherichia coli. Echinochrome was administered intravenously in 10, 1, or 0.1 mg/kg doses suspended in PBS (controls were injected with PBS only). Twenty-four hours after LPS injection, the number of infiltrating cells and the protein concentration in aqueous humor were determined. Aqueous tumor necrosis factor α (TNF-α) concentration was quantified with enzyme-linked immunosorbent assay, eyes were stained with nuclear factor (NF) κB antibodies, and ROS production was determined by dihydroethidium staining in fresh frozen samples.
  
  
  RESULTS
  The number of inflammatory aqueous cells and protein levels were lower in the groups treated with 10 and 1 mg/kg of echinochrome than in the untreated LPS group (p<0.01). Treatment with 10 and 1 mg/kg of echinochrome significantly reduced TNF-α concentrations in aqueous humor (p<0.01). The numbers of NFκB-positive cells and ROS signals were also reduced by echinochrome administration (p<0.05).
  
  
  CONCLUSIONS
  Echinochrome ameliorated intraocular inflammation caused by EIU by reducing ROS production, thereby also decreasing the expression of NFκB and TNF-α. As a natural pigment, echinochrome may therefore be a promising candidate for the safe treatment of intraocular inflammation. The use of sea urchin shells and spines in health foods and medical products is thus both economically and environmentally meaningful.
authors: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Anton
authors: A
authors: Lennikov
authors: Department of Ocular Inflammation and Immunology, Hokkaido University Graduate School of Medicine, Sapporo, Japan ; Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo, Japan.
authors: Nobuyoshi
authors: N
authors: Kitaichi
authors: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Kousuke
authors: K
authors: Noda
authors: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Kazuomi
authors: K
authors: Mizuuchi
authors: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Ryo
authors: R
authors: Ando
authors: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Zhenyu
authors: Z
authors: Dong
authors: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Junichi
authors: J
authors: Fukuhara
authors: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Satoshi
authors: S
authors: Kinoshita
authors: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Kenichi
authors: K
authors: Namba
authors: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Shigeaki
authors: S
authors: Ohno
authors: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan ; Department of Ocular Inflammation and Immunology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Susumu
authors: S
authors: Ishida
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D004731:Endotoxins; D007150:Immunohistochemistry; D007267:Injections; D007536:Isomerism; D008070:Lipopolysaccharides; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009285:Naphthoquinones / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species / Q000378:metabolism; D012617:Sea Urchins / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced* / Q000188:drug therapy*
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C007573:echinochrome A