Pyridoxamine inhibits early renal
disease and dyslipidemia in the streptozotocin-diabetic rat.
Degenhardt TP, Alderson NL, Arrington
DD, Beattie RJ,
Basgen JM, Steffes MW, Thorpe SR, Baynes JW.
Department of Chemistry, Animal Resource
Facility
University of South Carolina,
Columbia, SC 29208, USA.
Kidney Int. 2002 Mar;61(3):939-50.
Abstract
BACKGROUND: Nonenzymatic reactions
between sugars or lipids and protein and formation of advanced glycation
and lipoxidation end products (AGE/ALEs) contribute to the chemical
modification and cross-linking of tissue proteins with age. Accelerated
formation of AGE/ALEs during hyperglycemia is implicated in the
development of diabetic complications. In this study, we examined the
effect of the AGE/ALE inhibitor pyridoxamine on chemical modification
and cross-linking of collagen and development of renal disease in the
streptozotocin-diabetic rat.
METHODS: Diabetic rats were treated with pyridoxamine; parallel
experiments were conducted with aminoguanidine, the prototype AGE
inhibitor. Progression of renal disease was evaluated by measurements of
albuminuria and plasma creatinine concentration. Plasma triglycerides,
cholesterol, lactate and pyruvate were measured by enzymatic assays, and
AGE/ALEs in skin collagen by HPLC and GC-MS assays.
RESULTS: Pyridoxamine significantly inhibited the increase in
albuminuria, plasma creatinine, hyperlipidemia and plasma
lactate/pyruvate ratio in diabetic rats, without an effect on blood
glucose or glycated hemoglobin. AGE/ALEs, fluorescence and cross-linking
of skin collagen increased approximately twofold in diabetic versus
control rats after seven months of diabetes. Pyridoxamine caused a
significant (25 to 50%) decrease the AGE/ALEs, carboxymethyllysine and
carboxyethyllysine, cross-linking and fluorescence in skin collagen of
diabetic rats, but did not affect pentosidine.
CONCLUSIONS: Pyridoxamine inhibits the progression of renal disease, and
decreases hyperlipidemia and apparent redox imbalances in diabetic rats.
Pyridoxamine and aminoguanidine had similar effects on parameters
measured, supporting a mechanism of action involving AGE/ALE inhibition.
