The AGE inhibitor pyridoxamine inhibits lipemia and development of renal and vascular disease in Zucker obese rats

Kidney Int. 2003 Jun;63(6):2123-33. doi: 10.1046/j.1523-1755.2003.00027.x.


Background: In previous studies, pyridoxamine (PM) limited the formation of advanced glycation end products (AGEs) and development of nephropathy in streptozotocin-diabetic rats without affecting glycemic control. However, the lipid-lowering effects of PM and the correlation of plasma cholesterol and triglycerides with AGEs in skin collagen suggested that lipids might be an important source of AGEs in the diabetic rat. This study addresses the effects of hyperlipidemia on formation of advanced glycation and lipoxidation end products (AGE/ALEs) and the effects of PM on hyperlipidemia, hypertension, AGE/ALE formation, and development of nephropathy in the nondiabetic, Zucker obese rat.

Methods: Three groups of Zucker rats were studied: lean (Fa/fa), untreated fatty (fa/fa), and fa/fa treated with PM (2 g/L drinking water). Blood pressure, plasma lipids and creatinine, and urinary albumin were measured monthly. AGE/ALEs were measured in skin collagen by high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). Changes in wall thickness of the aorta and renal arterioles were evaluated by light microscopy.

Results: AGE/ALEs formation was increased two- to threefold in skin collagen of obese versus lean rats. PM inhibited the increases in AGE/ALEs in collagen, and significantly decreased the rise in plasma triglycerides, cholesterol, and creatinine, corrected hypertension and thickening of the vascular wall, and nearly normalized urinary protein and albumin excretion in Zucker fa/fa rats.

Conclusion: Lipids are an important source of chemical modification of tissue proteins, even in the absence of hyperglycemia. PM inhibited AGE/ALE formation and hyperlipidemia and protected against renal and vascular pathology in a nondiabetic model.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta / pathology
  • Arginine / analogs & derivatives*
  • Arginine / antagonists & inhibitors
  • Arginine / blood
  • Blood Glucose
  • Blood Pressure
  • Collagen / metabolism
  • Female
  • Glycation End Products, Advanced / antagonists & inhibitors*
  • Glycation End Products, Advanced / blood
  • Hyperlipidemias / blood
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / pathology
  • Hypertension / blood
  • Hypertension / pathology
  • Hypertension / prevention & control*
  • Kidney / pathology
  • Kidney / physiology
  • Kidney Diseases / blood
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • Lysine / analogs & derivatives*
  • Lysine / antagonists & inhibitors
  • Lysine / blood
  • Pyridoxamine / pharmacology*
  • Rats
  • Rats, Zucker
  • Skin / metabolism
  • Weight Gain / drug effects


  • Blood Glucose
  • Glycation End Products, Advanced
  • Pyridoxamine
  • Collagen
  • Arginine
  • pentosidine
  • Lysine