Luteolin attenuates endotoxin-induced uveitis in Lewis rats
2016
Kanai, K. (University of Kitasato, Towada, Aomori (Japan). School of Veterinary Medicine, Department of Small Animal Internal Medicine I) | Hatta, T. | Nagata, S. | Sugiura, Y. | Sato, K. | Yamashita, Y. | Kimura, Y. | Itoh, N.
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)-alpha, 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)-kappaB p65, I kappa B (IkappaB)-alpha degradation, phosphorylated (p)-IkappaB kinase (IKK) alpha/beta 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-alpha, 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-kappaB p65, IkappaB-alpha degradation, p-IKKalpha/beta 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-kappaB pathway and at least partly AP-1 activity in the ICB.
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