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Trientine and renin-angiotensin system blockade ameliorate progression of glomerular morphology in hypertensive experimental diabetic nephropathy.
MedLine Citation:
PMID:  22029676     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
A comparison of the efficacy of the copper chelator, trientine, with combined renin angiotensin system (RAS) blockade on the progression of glomerular pathology in the diabetic (mREN-2)27 rat is reported. Animals were treated for 2 months with trientine, combined RAS blockers, combined trientine plus RAS blockers or none. Treatments began after inducing diabetes with streptozotocin. Physiological data were recorded monthly and light microscopic glomerular features were scored. Plasma allantoin and both plasma and renal protein carbonyls were measured as markers of oxidative stress. Trientine and RAS blockade decreased proteinuria and albuminuria and prevented an increase in creatinine clearance and kidney weight. Both reduced the diabetes-related glomerular features of mesangiolysis and glomerular segmental hypocellularity and trientine prevented severe tuft-to-capsule adhesion and reduced tubularization. Hypertension-related severe mesangial matrix expansion and global hypercellularity were increased by both treatments, which may reflect repair of mesangiolysis. Trientine reduced plasma but not renal protein carbonyls or plasma allantoin. In this model, trientine prevented the development of many diabetes-specific features similarly to RAS blockade. Amelioration of oxidative stress and features commonly observed in human diabetic nephropathy (DN), support a diabetes-related defect in copper (Cu) metabolism. The addition of Cu(II) chelation may improve current DN therapy.
Authors:
Leire Moya-Olano; Helen Marie Milne; Jillian Margaret Robinson; Jonathan Vernon Hill; Christopher Miles Frampton; Helen Frances Abbott; Rufus Turner; Anthony James Kettle; Zoltán Huba Endre
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pathology international     Volume:  61     ISSN:  1440-1827     ISO Abbreviation:  Pathol. Int.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9431380     Medline TA:  Pathol Int     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  652-61     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
Affiliation:
Departments of Medicine Pathology, University of Otago-Christchurch, Christchurch, New Zealand Department of Nephrology and Hypertension, University of Cincinnati College of Medicine, Cincinnati, Ohio Division of Nephrology, University of Colorado, Denver, Colorado Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
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