Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo.
OBJECTIVE
Astaxanthin (AST) is a carotenoid that is found in marine animals and vegetables. Several previous studies have demonstrated that AST exhibits a wide variety of biological activities including antioxidant, antitumor, and anti-Helicobacter pylori effects. In this study, attention was focused on the antioxidant effect of AST. The object of the present study was to investigate the efficacy of AST in endotoxin-induced uveitis (EIU) in rats. In addition, the effect of AST on endotoxin-induced nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor (TNF)-alpha production in a mouse macrophage cell line (RAW 264.7) was studied in vitro.


METHODS
EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). AST or prednisolone was administered intravenously at 30 minutes before, at the same time as, or at 30 minutes after LPS treatment. The number of infiltrating cells and protein concentration in the aqueous humor collected at 24 hours after LPS treatment was determined. RAW 264.7 cells were pretreated with various concentrations of AST for 24 hours and subsequently stimulated with 10 microg/mL of LPS for 24 hours. The levels of PGE2, TNF-alpha, and NO production were determined in vivo and in vitro.


RESULTS
AST suppressed the development of EIU in a dose-dependent fashion. The anti-inflammatory effect of 100 mg/kg AST was as strong as that of 10 mg/kg prednisolone. AST also decreased production of NO, activity of inducible nitric oxide synthase (NOS), and production of PGE2 and TNF-alpha in RAW264.7 cells in vitro in a dose-dependent manner.


CONCLUSIONS
This study suggests that AST has a dose-dependent ocular anti-inflammatory effect, by the suppression of NO, PGE2, and TNF-alpha production, through directly blocking NOS enzyme activity.
Ohgami
Kazuhiro
K
Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, Sapporo, Japan. kohgami@med.hokudai.ac.jp
Shiratori
Kenji
K
Kotake
Satoshi
S
Nishida
Tomomi
T
Mizuki
Nobuhisa
N
Yazawa
Kazunaga
K
Ohno
Shigeaki
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001082:Aqueous Humor / Q000378:metabolism; D002452:Cell Count; D002460:Cell Line; D002470:Cell Survival; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D012486:Salmonella typhimurium; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D024341:Xanthophylls; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000975:Antioxidants; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D024341:Xanthophylls; D019207:beta Carotene; D009569:Nitric Oxide; C005948:astaxanthine; D011239:Prednisolone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D015232:Dinoprostone