Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat

modification and cross-linking of tissue proteins with age. Accelerated formation of AGE/ALEs during hyperglycemia is such as fructoselysine. The Amadori product is a precurimplicated in the development of diabetic complications. In sor to AGEs, which are a more permanent, irreversible this study, we examined the effect of the AGE/ALE inhibitor modification of proteins. According to the AGE hypothpyridoxamine on chemical modification and cross-linking of esis [1, 2], the increased rate of chemical modification collagen and development of renal disease in the streptozotocin-diabetic rat. and cross-linking of tissue proteins during hyperglycemia Methods. Diabetic rats were treated with pyridoxamine; par- compromises the structure and function of proteins and allel experiments were conducted with aminoguanidine, the contributes to the development of chronic complications prototype AGE inhibitor. Progression of renal disease was in diabetes. The accumulation of AGEs in collagen, a evaluated by measurements of albuminuria and plasma creatilong-lived protein in the extracellular matrix, is thought nine concentration. Plasma triglycerides, cholesterol, lactate and pyruvate were measured by enzymatic assays, and AGE/ to effect changes in elasticity, ionic charge, thickness and ALEs in skin collagen by HPLC and GC-MS assays. turnover of basement membrane components, setting Results. Pyridoxamine significantly inhibited the increase in the stage for development of diabetic renal, retinal and albuminuria, plasma creatinine, hyperlipidemia and plasma lac- vascular disease. tate/pyruvate ratio in diabetic rats, without an effect on blood glucose or glycated hemoglobin. AGE/ALEs, fluorescence and Reactive carbonyl and dicarbonyl compounds derived cross-linking of skin collagen increased approximately twofold from sugars are intermediates in the formation of AGEs, in diabetic versus control rats after seven months of diabetes. and oxygen, redox active transition metal ions and reacPyridoxamine caused a significant (25 to 50%) decrease the tive oxygen species are recognized as catalysts of AGE AGE/ALEs, carboxymethyllysine and carboxyethyllysine, crossformation [3]. The precise chemical origin of specific linking and fluorescence in skin collagen of diabetic rats, but did not affect pentosidine. AGEs is not always clear. Some AGEs, such as pentosiConclusions. Pyridoxamine inhibits the progression of renal dine, are clearly derived from carbohydrates, but may disease, and decreases hyperlipidemia and apparent redox im- be formed from glucose, ascorbate, 3-deoxyglucosone balances in diabetic rats. Pyridoxamine and aminoguanidine or other sugars in vivo [4]. The major AGEs, including had similar effects on parameters measured, supporting a the lysine adducts N e