Trientine and renin-angiotensin system blockade ameliorate progression of glomerular morphology in hypertensive experimental diabetic nephropathy

• Published in: Pathology international Vol. 61; no. 11; pp. 652 - 661
• Main Authors: Moya-Olano, Leire, Milne, Helen Marie, Robinson, Jillian Margaret, Hill, Jonathan Vernon, Frampton, Christopher Miles, Abbott, Helen Frances, Turner, Rufus, Kettle, Anthony James, Endre, Zoltán Huba
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.11.2011
• Subjects: Allantoin - blood; Animals; Chelating Agents - pharmacology; Copper - metabolism; copper(II) chelation; Creatinine - metabolism; Diabetes Mellitus, Experimental - complications; Diabetic Nephropathies - chemically induced; Diabetic Nephropathies - pathology; Diabetic Nephropathies - physiopathology; diabetic nephropathy; Disease Models, Animal; Disease Progression; Female; Heterozygote; Humans; Hypertension - complications; Kidney - drug effects; Kidney - pathology; Kidney - physiopathology; Kidney Glomerulus - drug effects; Kidney Glomerulus - pathology; Kidney Glomerulus - physiopathology; light microscopy; Male; morphometry; Oxidative Stress; Proteinuria - prevention & control; Rats; Rats, Sprague-Dawley; Rats, Transgenic; renin-angiotensin system; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology; Streptozocin; Trientine - pharmacology
• ISSN: 1320-5463; 1440-1827
• DOI: 10.1111/j.1440-1827.2011.02721.x

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 CuII chelation may improve current DN therapy