Effects of Oral 5-Aminolevulinic Acid on Lipopolysaccharide-Induced Ocular Inflammation in Rats

Abstract

This study aimed to investigate the anti-inflammatory effect of 5-aminolevulinic acid (5-ALA) on endotoxin-induced uveitis (EIU) in rats. EIU was induced in male Sprague Dawley rats by the subcutaneous injection of lipopolysaccharide (LPS). During LPS injection, 5-ALA diluted with saline was administered via gastric gavage. After 24 h, clinical scores were assessed after which aqueous humor (AqH) samples were obtained. The number of infiltrating cells, protein concentration, and levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E2 (PGE2) in AqH were measured. For histological examination, both eyes of some rats were enucleated. In vitro, a mouse macrophage cell line (RAW264.7 cells) was stimulated by LPS with or without 5-ALA. Western blot was used to analyze the expression of inducible NO synthase (iNOS) and cyclooxygenase-2. 5-ALA suppressed the EIU clinical scores, infiltrating cell number, and protein concentration while improving the histopathologic scores. In particular, 100 mg/kg 5-ALA reduced the concentrations of NO, PGE2, TNF-α, and IL-6 in AqH, similar to 1 mg/kg prednisolone. In addition, 5-ALA suppressed iNOS upregulation in LPS-stimulated RAW264.7 cells. Therefore, 5-ALA has an anti-inflammatory effect on EIU through the inhibition of the upregulation of inflammatory mediators.