Linked Life Data

20554645

Source:http://linkedlifedata.com/resource/pubmed/id/20554645

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-9-3
pubmed:abstractText
Diabetic nephropathy is a leading cause of end-stage renal disease. Statins may exert renoprotective effects independently of lipid-lowering properties. We investigated the pleiotropic effects of rosuvastatin on renal structure and function in streptozotocin diabetic apolipoprotein-E knockout (Apo-E(-/-)) mice, a model of progressive nephropathy in which dyslipidemia is resistant to statin treatment. These effects were compared with those observed with conventional renin-angiotensin system blockade (candesartan) or combined treatment. Nondiabetic and diabetic Apo-E(-/-) mice were randomized to no treatment or treatment with candesartan (2.5 mg/kg), rosuvastatin (5 mg/kg), or their combination per gavage for 20 wk. Urine and blood samples were collected for assessment of albuminuria, creatinine clearance, plasma lipids, glucose, and glycated hemoglobin. Renal sclerosis was analyzed on paraffin-embedded kidney sections stained with periodic acid-Schiff. Renal expression of collagen IV, fibronectin and advanced glycation end products (AGEs), receptor for advanced glycation and products (RAGE), NADPH oxidase 4 (NOX4), and nitrotyrosine was assessed by real-time PCR and/or immunohistochemistry. Diabetes-induced albuminuria was not affected by rosuvastatin and combination treatment but was prevented by candesartan. Diabetes resulted in increased creatinine clearance, which was not modified by the treatments. Rosuvastatin and/or candesartan prevented diabetes-associated renal extracellular matrix accumulation. Rosuvastatin reduced accumulation of AGEs and expression of RAGE, NOX4, and nitrotyrosine. In conclusion, in the diabetic Apo-E(-/-) mouse, rosuvastatin confers renal benefits that are independent of lipid lowering and equivalent or greater to those observed with candesartan. The combination treatment is not superior to monotherapies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1522-1466
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F528-35
pubmed:dateRevised
2011-4-28
pubmed:meshHeading
pubmed-meshheading:20554645-Angiotensin II Type 1 Receptor Blockers, pubmed-meshheading:20554645-Animals, pubmed-meshheading:20554645-Apolipoproteins E, pubmed-meshheading:20554645-Benzimidazoles, pubmed-meshheading:20554645-Blood Pressure, pubmed-meshheading:20554645-Diabetes Mellitus, Experimental, pubmed-meshheading:20554645-Diabetic Nephropathies, pubmed-meshheading:20554645-Disease Models, Animal, pubmed-meshheading:20554645-Drug Therapy, Combination, pubmed-meshheading:20554645-Fluorobenzenes, pubmed-meshheading:20554645-Hydroxymethylglutaryl-CoA Reductase Inhibitors, pubmed-meshheading:20554645-Kidney, pubmed-meshheading:20554645-Lipid Metabolism, pubmed-meshheading:20554645-Male, pubmed-meshheading:20554645-Mice, pubmed-meshheading:20554645-Mice, Knockout, pubmed-meshheading:20554645-Oxidative Stress, pubmed-meshheading:20554645-Pyrimidines, pubmed-meshheading:20554645-Streptozocin, pubmed-meshheading:20554645-Sulfonamides, pubmed-meshheading:20554645-Tetrazoles
pubmed:year
2010
pubmed:articleTitle
The pleiotropic actions of rosuvastatin confer renal benefits in the diabetic Apo-E knockout mouse.
pubmed:affiliation
Baker IDI Heart and Diabetes Institute, Monash University, Melbourne, Australia.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't