The inhibition of retinal inducible nitric oxide synthase overexpression and the attenuation of experimental uveitis by anti-inflammatory drugs in rats

Inflamm Res. 2004 Jun;53(6):262-7. doi: 10.1007/s00011-004-1259-z. Epub 2004 May 12.

Abstract

Objective and design: The effect of a steroid and a non-steroid anti-inflammatory drug on the inducible nitric oxide synthase (NOS II) in rats suffering from lipopolysaccharide (LPS)-induced uveoretinitis was studied.

Treatments: Rats were injected with LPS to induce uveitis and divided into three groups: treated with LPS only, LPS + dexamethasone and LPS + indomethacin, respectively.

Methods: Retinal, peritoneal macrophages and white blood cells were isolated. The activity and the expression of NOS II were followed by citrulline formation and Western blotting, respectively. Phagocytosis of bacteria was also measured.

Results: The best induction of NOS II was achieved by the intravitreal administration of LPS. Dexamethasone and indomethacin significantly decreased the activity and the expression of inducible nitric oxide synthase in retinal tissue, peritoneal macrophages and white blood cells. LPS treatment also increased phagocytosis and neither dexamethasone nor indomethacin reversed this effect.

Conclusions: The beneficial effects of these drugs in experimental uveitis are mediated, at least partly, by their inhibitory effect on NOS II induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Blotting, Western
  • Citrulline / metabolism
  • Dexamethasone / pharmacology
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Female
  • Indomethacin / pharmacology
  • Inflammation
  • Leukocytes / metabolism
  • Lipopolysaccharides / metabolism
  • Macrophages / metabolism
  • Male
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase Type II
  • Phagocytosis
  • Rats
  • Rats, Wistar
  • Retina / enzymology*
  • Time Factors
  • Uveitis / drug therapy*

Substances

  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Citrulline
  • Dexamethasone
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Indomethacin