title: Preventive effects of ethyl pyruvate on endotoxin-induced uveitis in rats.
abstract: OBJECTIVE
  Recent studies indicate that ethyl pyruvate (EP) exerts anti-inflammatory properties; however, the effect of EP on ocular inflammation is not known. The efficacy of EP in endotoxin-induced uveitis (EIU) in rats was investigated.
  
  
  METHODS
  EIU in Lewis rats was developed by the subcutaneous injection of lipopolysaccharide (LPS; 150 μg). EP (30 mg/kg body weight) or its carrier was injected intraperitoneally 1 hour before or 2 hours after lipopolysaccharide injection. Animals were killed after 3 and 24 hours followed by enucleation of eyes and collection of the aqueous humor (AqH). The number of infiltrating cells and levels of proteins in the AqH were determined. The rat cytokine/chemokine multiplex method was used to determine level of cytokines and chemokines in the AqH. TNF-α and phospho-nuclear factor kappa B (NF-κB) expression in ocular tissues were determined immunohistochemically. Human primary nonpigmented ciliary epithelial cells (HNPECs) were used to determine the in vitro efficacy of EP on lipopolysaccharide-induced inflammatory response.
  
  
  RESULTS
  Compared to controls, AqH from the EIU rat eyes had a significantly higher number of infiltrating cells, total protein, and inflammatory cytokines/chemokines, and the treatment of EP prevented EIU-induced increases. In addition, EP also prevented the expression of TNF-α and activation of NF-κB in the ciliary bodies and retina of the eye. Moreover, in HNPECs, EP inhibited lipopolysaccharide-induced activation of NF-κB and expression of Cox-2, inducible nitric oxide synthase, and TNF-α.
  
  
  CONCLUSIONS
  Our results indicate that EP prevents ocular inflammation in EIU, suggesting that the supplementation of EP could be a novel approach for the treatment of ocular inflammation, specifically uveitis.
authors.affiliation: AMD Centre, Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Nilesh M
authors.initials: NM
authors.lastname: Kalariya
authors.forename: Aramati B M
authors.initials: AB
authors.lastname: Reddy
authors.forename: Naseem H
authors.initials: NH
authors.lastname: Ansari
authors.forename: Frederik J G M
authors.initials: FJ
authors.lastname: VanKuijk
authors.forename: Kota V
authors.initials: KV
authors.lastname: Ramana
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D002924:Ciliary Body / Q000166:cytology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism; D011773:Pyruvates / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011773:Pyruvates; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate; C044101:endotoxin, Escherichia coli; D051546:Cyclooxygenase 2