title: Oxidants, antioxidants and mitochondrial function in non-proliferative diabetic retinopathy.
abstract: BACKGROUND
  Diabetic retinopathy (DR) is a preventable cause of visual disability. The aims of the present study were to investigate levels and behavior oxidative stress markers and mitochondrial function in non-proliferative DR (NPDR) and to establish the correlation between the severity of NPDR and markers of oxidative stress and mitochondrial function.
  
  
  METHODS
  In a transverse analysis, type 2 diabetes mellitus (T2DM) patients with mild, moderate and severe non-proliferative DR (NPDR) were evaluated for markers of oxidative stress (i.e. products of lipid peroxidation (LPO) and nitric oxide (NO) catabolites) and antioxidant activity (i.e. total antioxidant capacity (TAC), catalase, and glutathione peroxidase (GPx) activity of erythrocytes). Mitochondrial function was also determined as the fluidity of the submitochondrial particles of platelets and the hydrolytic activity of F0 /F1 -ATPase.
  
  
  RESULTS
  Levels of LPO and NO were significantly increased in T2DM patients with severe NPDR (3.19 ± 0.05 μmol/mL and 45.62 ± 1.27 pmol/mL, respectively; P < 0.007 and P < 0.0001 vs levels in health volunteers, respectively), suggesting the presence of oxidative stress. TAC had significant decrease levels with minimum peak in severe retinopathy with 7.98 ± 0.48 mEq/mL (P < 0.0001). In contrast with TAC, erythrocyte catalase and GPx activity was increased in patients with severe NPDR (139.4 ± 4.4 and 117.13 ± 14.84 U/mg, respectively; P < 0.0001 vs healthy volunteers for both), suggesting an imbalance between oxidants and antioxidants. The fluidity of membrane submitochondrial particles decreased significantly in T2DM patients with mild, moderate, or severe NPDR compared with that in healthy volunteers (P < 0.0001 for all). Furthermore, there was a significant increase in the hydrolytic activity of the F0 /F1 -ATPase in T2DM patients with mild NPDR (265.07 ± 29.55 nmol/PO4 ; P < 0.0001 vs healthy volunteers), suggesting increased catabolism.
  
  
  CONCLUSIONS
  Patients with NPDR exhibit oxidative deregulation with decreased membrane fluidity of submitochondrial particles and increased systemic catabolism (mitochondrial dysfunction) with the potential for generalized systemic damage in T2DM.
authors.affiliation: University Health Sciences Centre, University of Guadalajara, Guadalajara, México.
authors.forename: Adolfo Daniel
authors.initials: AD
authors.lastname: Rodríguez-Carrizalez
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Castellanos-González
authors.forename: Esaú César
authors.initials: EC
authors.lastname: Martínez-Romero
authors.forename: Guillermo
authors.initials: G
authors.lastname: Miller-Arrevillaga
authors.forename: David
authors.initials: D
authors.lastname: Villa-Hernández
authors.forename: Pedro Pablo
authors.initials: PP
authors.lastname: Hernández-Godínez
authors.forename: Genaro Gabriel
authors.initials: GG
authors.lastname: Ortiz
authors.forename: Fermín Paul
authors.initials: FP
authors.lastname: Pacheco-Moisés
authors.forename: Ernesto Germán
authors.initials: EG
authors.lastname: Cardona-Muñoz
authors.forename: Alejandra Guillermina
authors.initials: AG
authors.lastname: Miranda-Díaz
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D015227:Lipid Peroxidation; D008297:Male; D008560:Membrane Fluidity; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000378:metabolism; D015999:Multivariate Analysis; D009569:Nitric Oxide / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016877:Oxidants; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D002374:Catalase; D005979:Glutathione Peroxidase; D006180:Proton-Translocating ATPases
keywords: diabetes mellitus; diabetic retinopathy; membrane fluidity; nitrosative stress; oxidative stress; 糖尿病，糖尿病视网膜病变，膜流动性，硝化应激，氧化应激