Effect of the Toll-like receptor 4 antagonist eritoran on retinochoroidal inflammatory damage in a rat model of endotoxin-induced inflammation

Mediators Inflamm. 2014:2014:643525. doi: 10.1155/2014/643525. Epub 2014 Jun 17.

Abstract

Purpose: We investigated the effect of eritoran, a Toll-like receptor 4 antagonist, on retinochoroidal inflammatory damage in an endotoxin-induced inflammatory rat model.

Methods: Endotoxin-induced inflammatory model was obtained by intraperitoneal injection of 1.5 mg/kg lipopolysaccharide (LPS). Group 1 had control rats; in groups 2-3 LPS and 0.5 mg/kg sterile saline were injected; and in groups 4-5 LPS and 0.5 mg/kg eritoran were injected. Blood samples were taken and eyes were enucleated after 12 hours (h) (groups 2 and 4) or 24 hours (Groups 3 and 5). Tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels in the serum and retinochoroidal tissue and nuclear factor kappa-B (NFκB) levels in retinochoroidal tissue were determined. Histopathological examination was performed and retinochoroidal changes were scored.

Results: Eritoran treatment resulted in lower levels of TNF-α, MDA, and NFκB after 12 h which became significant after 24 h. Serum TNF-α and retinochoroidal tissue NFκB levels were similar to control animals at the 24th h of the study. Eritoran significantly reversed histopathological damage after 24 h.

Conclusions: Eritoran treatment resulted in less inflammatory damage in terms of serum and retinochoroidal tissue parameters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disaccharides / therapeutic use*
  • Inflammation / chemically induced*
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Lipopolysaccharides / toxicity*
  • Male
  • Malondialdehyde / blood
  • Malondialdehyde / metabolism
  • NF-kappa B / blood
  • NF-kappa B / metabolism
  • Rats
  • Sugar Phosphates / therapeutic use*
  • Toll-Like Receptor 4 / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Disaccharides
  • Lipopolysaccharides
  • NF-kappa B
  • Sugar Phosphates
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • eritoran