The AGE inhibitor pyridoxamine
inhibits lipemia and development of renal and vascular disease in Zucker
obese rats.
Alderson NL, Chachich ME, Youssef NN,
Beattie RJ, Nachtigal M, Thorpe SR, Baynes JW.
Department of Chemistry and Biochemistry
Animal Resource Facility
University of South Carolina, Columbia, 29208.
Kidney Int. 2003 Jun;63(6):2123-33
Abstract
BACKGROUND: In previous studies,
pyridoxamine 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 pyridoxamine 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 pyridoxamine 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 pyridoxamine (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. Pyridoxamine 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. Pyridoxamine
inhibited AGE/ALE formation and hyperlipidemia and protected against
renal and vascular pathology in a nondiabetic model.
