Suppressive effects of astaxanthin against rat endotoxin-induced uveitis by inhibiting the NF-kappaB signaling pathway.
We investigated the effects of astaxanthin (AST), a carotenoid, on endotoxin-induced uveitis (EIU), and over the course of the disease measured the expression of inflammatory cytokines and chemokines in the presence or absence of AST. EIU was induced in male Lewis rats by footpad injection of lipopolysaccharide (LPS). The animals were randomly divided to 12 groups with eight animals in each. Immediately after the inoculation, AST (1, 10, or 100 mg kg(-1)) was injected intravenously. Aqueous humour was collected at 6, 12 and 24 hr after LPS inoculation and the number of infiltrating cells in the anterior chamber was counted. In addition, we assayed the concentration of protein, nitric oxide (NO), tumour necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2). Immunohistochemical staining with a monoclonal antibody against activated NF-kappaB was performed in order to evaluate the effects of AST on NF-kappaB activation. Rats injected with AST showed a significant decrease in the number of infiltrating cells in the anterior chamber and additionally there was a significantly lower concentration of protein, NO, TNF-alpha and PGE2 in the aqueous humour. Moreover, even early stages of EIU were suppressed by injection of AST. The number of activated NF-kappaB-positive cells was lower in iris-ciliary bodies treated with 10 or 100 mg kg(-1) AST at 3 hr after LPS injection. These results suggest that AST reduces ocular inflammation in eyes with EIU by downregulating proinflammatory factors and by inhibiting the NF-kappaB-dependent signaling pathway.
Suzuki
Yukari
Y
Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, N15 W7, Sapporo 060-8638, Japan.
Ohgami
Kazuhiro
K
Shiratori
Kenji
K
Jin
Xue-Hai
XH
Ilieva
Iliyana
I
Koyama
Yoshikazu
Y
Yazawa
Kazunaga
K
Yoshida
Kazuhiko
K
Kase
Satoru
S
Ohno
Shigeaki
S
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001082:Aqueous Humor / Q000276:immunology / Q000378:metabolism*; D002924:Ciliary Body / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003864:Depression, Chemical; D015232:Dinoprostone / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry / Q000379:methods; D007498:Iris / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000032:analysis; D009573:Nitrites / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D024341:Xanthophylls; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D024341:Xanthophylls; D019207:beta Carotene; D009569:Nitric Oxide; C005948:astaxanthine; D015232:Dinoprostone