title: Atorvastatin-mediated protection of the retina in a model of diabetes with hyperlipidemia.
abstract: Insulin resistance, a key feature of obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM), results in a variety of metabolic and vascular abnormalities. Metabolic disturbances associated with diabetes could contribute to disrupting the structural and (or) functional integrity of the retina. The effects of atorvastatin on retinal cells in hyperlipidemic T2DM rats have not yet been investigated. We used Goto-Kakizaki (GK) rats fed with an atherogenic diet (AD) for 4 months to investigate whether atorvastatin (administered for 1 month) would slow-down or reverse the progression of lesions in the diabetic retina. Fluorogenic substrates were used to measure the proteasome activities in retinal cells. The production of reactive oxygen species was determined by immunofluorescence in frozen retina sections, using dihydroethydium. Nitrotyrosine levels were assessed using immunohistochemistry. Protein levels of ubiquitin conjugates, free ubiquitin, and ubiquitin activating enzyme E1 were determined with Western blotting. Atorvastatin significantly reduced the levels of oxidative stress that were induced by the AD and restored the proteasome activities in the diabetic GK rats. Atorvastatin therapy significantly improved local oxidative stress levels in GK rats fed with AD. Atorvastatin can, at least in part, restore the ubiquitin proteasome system, and may represent a pharmacological approach to prevent some of the complications associated with diabetic retinopathy.
authors.affiliation: a Centre of Opththalmology and Vision Sciences - Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Rosa
authors.initials: R
authors.lastname: Fernandes
authors.forename: Carla F
authors.initials: CF
authors.lastname: Bento
authors.forename: Paulo
authors.initials: P
authors.lastname: Matafome
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Sena
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Seiça
authors.forename: Paulo
authors.initials: P
authors.lastname: Pereira
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D000069059:Atorvastatin; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004036:Diet, Atherogenic; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D006538:Heptanoic Acids; D011758:Pyrroles; D017382:Reactive Oxygen Species; D025801:Ubiquitin; D000069059:Atorvastatin; D046988:Proteasome Endopeptidase Complex
keywords: atherogenic diet; diabetic retinopathy; diète athérogène; oxidative stress; proteasome; protéasome; rétinopathie diabétique; statines; statins; stress oxydant