title: Effect of N-acetylcysteine on the early expression of inflammatory markers in the retina and plasma of diabetic rats.
abstract: OBJECTIVE
  The aim of this study is to investigate markers of inflammation and oxidative stress in an early model of diabetic retinopathy, correlate retinal and plasma results and evaluate the influence of treatment by N-acetylcysteine (NAC), a free radical scavenger.
  
  
  METHODS
  Four groups were studied: control (C), streptozotocin (STZ)-induced diabetic rats (D), STZ rats following 8 weeks of NAC (DT), and control rats following 8 weeks of NAC (CT). Plasma levels of free 15-F2t-isoprostane (15-F-2t-IsoP), superoxide dismutase (SOD) and tumour necrosis factor-alpha (TNF-alpha) were obtained. Primary antibodies against macrophages (ED-1), microglia (Ox-42), pericytes (NG-2), endothelial and perivascular cells (IB-4), haem oxygenase 1 (HO-1) and vascular endothelial growth factor (VEGF) were used.
  
  
  RESULTS
  Expression of NG-2 was robust in C, CT, DT, and mild in D. The intensity of IB-4 was higher in D and DT compared with the C and CT. Ox-42 and ED-1 expression was higher in the D than in the DT, C or CT. Expression of VEGF and HO-1 was non-specific across the four groups. Plasma levels of 15-F-2t-IsoP and TNF-alpha were higher in the D as compared with the C, CT and DT. SOD levels were lower in the D when compared with the C, CT and D.
  
  
  CONCLUSIONS
  Macrophage/microglia activation, pericyte loss and endothelial/perivascular cell changes occur early in the pathogenesis of DR. These changes are associated with an increase in plasma markers of oxidative stress and inflammation and are minimized by treatment with NAC. The results suggest that therapies that reduce free radicals will help minimize the early events in diabetic retinopathy in the STZ model.
authors.affiliation: Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Columbia, Canada.
authors.forename: Gina Y
authors.initials: GY
authors.lastname: Tsai
authors.forename: Jing Z
authors.initials: JZ
authors.lastname: Cui
authors.forename: Husnain
authors.initials: H
authors.lastname: Syed
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.forename: Ugur
authors.initials: U
authors.lastname: Ozerdem
authors.forename: John H
authors.initials: JH
authors.lastname: McNeill
authors.forename: Joanne A
authors.initials: JA
authors.lastname: Matsubara
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015237:Dinoprost / Q000031:analogs & derivatives; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D028421:Isoprostanes / Q000097:blood; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D020286:Pericytes / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D016166:Free Radical Scavengers; D028421:Isoprostanes; D014409:Tumor Necrosis Factor-alpha; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D013482:Superoxide Dismutase; D000111:Acetylcysteine