Luteolin attenuates endotoxin-induced uveitis in Lewis rats.
The aim of the present study was to investigate the efficacy of luteolin on endotoxin-induced uveitis (EIU) in rats. EIU was induced in Lewis rats by subcutaneous injections of lipopolysaccharide (LPS). One hr before the LPS injection, 0.1, 1 or 10 mg/kg luteolin or 1 mg/kg prednisolone was intraperitoneally injected. We investigated its effect upon clinical scores, cellular infiltration and protein leakage, as well as on the level of tumor necrosis factor (TNF)-α, nitric oxide (NO) and prostaglandin (PG) E2 in the aqueous humor (AqH). Histologic examination and immunohistochemical analysis in the iris-ciliary body (ICB) were performed to determine the expressions of cyclooxygenase (COX)-2 and inducible NO synthase (iNOS), and then the activated nuclear factor (NF)-κB p65, I kappa B (IκB)-α degradation, phosphorylated (p)-IκB kinase (IKK) α/β and activator protein (AP)-1 c-Jun. Luteolin suppressed, in a dose-dependent manner, the clinical scores, number of inflammatory cells, the protein concentration, and the TNF-α, NO and PGE2 levels in the AqH and improved the histiologic status of the ocular tissue. Luteolin suppressed the expression of iNOS and COX-2 and the activated NF-κB p65, IκB-α degradation, p-IKKα/β and AP-1 p-c-Jun in the ICB. The anti-inflammatory potency of 10 mg/kg luteolin was as strong as that observed with 1 mg/kg prednisolone. These results demonstrate that luteolin attenuates ocular inflammation by inhibiting expression and release of inflammatory markers, along with the inhibition of the activated NF-κB pathway and at least partly AP-1 activity in the ICB.
Department of Small Animal Internal Medicine I, School of Veterinary Medicine, University of Kitasato, Towada, Aomori 034-8628, Japan.
Kazutaka
K
Kanai
Takuya
T
Hatta
Sho
S
Nagata
Yuichi
Y
Sugiura
Kazuaki
K
Sato
Yohei
Y
Yamashita
Yuya
Y
Kimura
Naoyuki
N
Itoh
D000818:Animals; D004195:Disease Models, Animal; D004731:Endotoxins / Q000494:pharmacology; D047311:Luteolin / Q000627:therapeutic use*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D011917:Rats, Inbred Lew; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014602:Uvea / Q000378:metabolism / Q000473:pathology; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*
D004731:Endotoxins; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D047311:Luteolin