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The Metal Chelators, Trientine and Citrate, Inhibit the Development of Cardiac Pathology in the Zucker Diabetic Rat

By John W. Baynes and David B. Murray


Purpose. The objective of this study was to determine the efficacy of dietary supplementation with the metal chelators, trientine or citric acid, in preventing the development of cardiomyopathy in the Zucker diabetic rat. Hypothesis. We hypothesized that dietary chelators would attenuate metal-catalyzed oxidative stress and damage in tissues and protect against pathological changes in ventricular structure and function in type II diabetes. Methods. Animals (10 weeks old) included lean control (LC, fa/+), untreated Zucker diabetic fatty (ZDF, fa/fa), and ZDF rats treated with either trientine (triethylenetetramine) or citrate at 20 mg/d in drinking water, starting when rats were frankly diabetic. Cardiac functional assessment was determined using a Millar pressure/volume catheter placed in the left ventricle at 32 weeks of age. Results. End diastolic volume for the ZDF animals increased by 36% indicating LV dilatation (P < .05) and was accompanied by a 30% increase in the end diastolic pressure (P ≤ .05). Both trientine and citric acid prevented the increases in EDV and EDP (P < .05). Ejection fraction and myocardial relaxation were also significantly improved with chelator treatment. Conclusion. Dietary supplementation with trientine and citric acid significantly prevented structural and functional changes in the diabetic heart, supporting the merits of mild chelators for prevention of cardiovascular disease in diabetes

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Publisher: Hindawi Publishing Corporation
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    1. (2005). A copper chelating agent suppresses carbonyl stress in diabetic rat lenses,”
    2. (2007). a n dG .J .S .C o o p e r ,“ T r i e t h y l e n e t e t r a m i n ea n dm e t a b o l i t e s : levels in relation to copper and zinc excretion in urine of healthy volunteers and type 2 diabetic patients,” Drug Metabolism and Disposition,
    3. (2003). AGE-breakers cleavemodelcompounds,butdonotbreakMaillardcrosslinks in skin and tail collagen from diabetic rats,”
    4. (2003). Analysis of the Zucker Diabetic Fatty (ZDF) type 2 diabetic rat model suggests a neurotrophic role for insulin/IGFI in diabetic autonomic neuropathy,”
    5. (2001). C o p p e y ,J .S .G e l l e t t ,E .P .D a v i d s o n ,J .A .D u n l a p
    6. (1999). Chelation therapy for patients with elevated body lead burden and progressive renal insufficiency: a randomized, controlled trial,”
    7. (2002). Concentric versus eccentric remodeling,”
    8. (2004). Crosslink breakers: a new approach to cardiovascular therapy,”
    9. (2005). e n n a t h u r ,Y .I d o ,J .I .H e l l e r ,e ta l . ,“ R e a c t i v ec a r b o n y l s and polyunsaturated fatty acids produce a hydroxyl radicallikespecies:apotentialpathwayforoxidativedamageofretinal proteins in diabetes,”
    10. (2001). Effects of an extracellular metal chelator on neurovascular function in diabetic rats,”
    11. (1999). Effects of chelator treatment on aorta and corpus cavernosum from diabetic rats,”
    12. (2008). Effects of nonselective endothelin-1 receptor antagonism on cardiac mast cell-mediated ventricular remodeling in rats,”
    13. (2002). Effects of trientine, a metal chelator, on defective endotheliumdependent relaxation in the mesenteric vasculature of diabetic rats,”
    14. (2004). Elevated iron indices in patients with diabetes,”
    15. (2007). Fe 2+-catalyzed non-enzymatic glycosylation alters collagen conformation during AGEcollagen formation in vitro,”
    16. (2000). Glycoxidation and lipoxidation in atherogenesis,”
    17. (1976). Hemodynamic determinants of the time course of fall in canine left ventricular pressure,”
    18. (2007). Impairment of sympathetic baroreceptor reflexes in obese Zucker rats,”
    19. (2006). Inhibitors of the Maillard reaction and AGE breakers as therapeutics for multiple diseases,” Drug Discovery Today,
    20. (2005). Left ventricular hypertrophy and preclinical impaired glucose tolerance and diabetes mellitus contribute to abnormal left ventricular diastolic function in hypertensive patients,”
    21. (2005). Left ventricular hypertrophy in normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment,”
    22. (2007). Mechanisms for oxidative stress in diabetic cardiovascular disease,”
    23. (2006). Molecular changes evoked by triethylenetetramine treatment in the extracellular matrix of the heart and aorta in diabetic rats,”
    24. (2004). o o p e r ,A .R .J .P h i l l i p s ,S .Y .C h o o n g ,e ta l . , “Regeneration of the heart in diabetes by selective copper chelation,”
    25. (2008). Oxidative stress and iron homeostasis: mechanistic and health aspects,”
    26. (2001). P r i c e ,P .M .R h e t t ,S .R .T h o r p e ,a n dJ
    27. (2006). Reactive species, cellular repair and risk factors in the onset of type 2 diabetes mellitus: reviewandhypothesis,”CurrentDiabetesReviews,vol.2,no.2,
    28. (2002). Receptor for advanced glycation endproducts (RAGE) and the complications of diabetes,”
    29. (1999). Role of oxidative stress in diabetic complications: a new perspective on an old paradigm,”
    30. (2003). S.RahbarandJ.L.Figarola,“Novelinhibitorsofadvancedglycation endproducts,”
    31. Serum ferritin levels in poorly- and well-controlled diabetes mellitus,”EndocrineResearch,vol.29,no.3,pp.299–306,2003.
    32. (2005). T h o m a s ,J .W .B a y n e s ,S .R .T h o r p e ,a n dM .E . Cooper, “The role of AGEs and AGE inhibitors in diabetic cardiovascular disease,” Current Drug Targets,v o l .6 ,n o .4 ,p p .
    33. (2001). The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses,”
    34. The role of metal-catalyzed oxidation in the formation of advanced glycation end products: an in vitro study on collagen,” Free RadicalBiologyandMedicine,vol.25,no.3,pp.265–269,1998.
    35. (2008). The role of zinc, copper and iron in the pathogenesis of diabetes and diabetic complications: therapeutic effects by chelators,”
    36. (2005). Understanding RAGE, the receptor for advanced glycation end products,”
    37. w a m i n a t h a n ,V .A .F o n s e c a ,M .G .A l a m ,a n dS .V .S h a h , “The role of iron in diabetes and its complications,” Diabetes Care,

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