title: Tyrosol ameliorates lipopolysaccharide-induced ocular inflammation in rats via inhibition of nuclear factor (NF)-κB activation.
abstract: We evaluated the anti-inflammatory effect of tyrosol (Tyr) on endotoxin-induced uveitis (EIU) in rats. EIU was induced in male Lewis rats by subcutaneous injection of lipopolysaccharide (LPS). Tyr (10, 50 or 100 mg/kg) was intravenously injected 2 hr before, simultaneously and 2 hr after LPS injection. The aqueous humor (AqH) was collected 24 hr after LPS injection; the infiltrating cell number, protein concentration, and tumor necrosis factor (TNF)-α, prostaglandin (PG)-E2 and nitric oxide (NO) levels were determined. Histopathologic examination and immunohistochemical studies for nuclear factor (NF)-κB, inhibitor of κB (IκB)-α, cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) in the iris-ciliary body (ICB) were performed at 3 or 24 hr after LPS injection. To further clarify the anti-inflammatory effects, RAW264.7 macrophages were stimulated with LPS in the presence or absence of Tyr. Tyr reduced, in a dose-dependent manner, the infiltrating cell number, protein concentration, and TNF-α, PGE2 and NO levels in AqH and improved histopathologic scores of EIU. Tyr also inhibited LPS-induced COX-2 and iNOS expression, IκB-α degradation and nuclear translocation of activated NF-κB in ICB. Tyr significantly suppressed inflammatory mediator production in the culture medium and COX-2 and iNOS expression and activated NF-κB translocation in LPS-stimulated RAW264.7 cells. These results suggest that Tyr suppresses ocular inflammation of EIU by inhibiting NF-κB activation and subsequent proinflammatory mediator production.
authors.affiliation: Department of Small Animal Internal Medicine I, School of Veterinary Medicine, University of Kitasato, 35-1, Towada, Aomori 034-8628, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Sato
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mihara
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Kanai
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kimura
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Itoh
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001082:Aqueous Humor / Q000737:chemistry / Q000166:cytology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000032:analysis / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000067996:RAW 264.7 Cells / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; C011867:4-hydroxyphenylethanol; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D010626:Phenylethyl Alcohol