Aminoguanidine inhibits albuminuria, but not the formation of advanced glycation end-products in skin collagen of diabetic rats

Aminoguanidine, an inhibitor of advanced glycation reactions in vitro, inhi bits the development of diabetic complications in animal models of diabetes , suggesting that it acts by inhibition of advanced glycation reactions in vivo. However, effects of aminoguanidine on the formation of specific advan ced glycation end-products (AGEs) in vivo have not been rigorously examined . Therefore, we studied the effects of aminoguanidine on the formation of p entosidine and N-epsilon-(carboxymethyl)lysine (CML), measured by analytica l chemical methods, in collagen of streptozotocin-diabetic Lewis rats at do ses which ameliorated urinary albumin excretion, an index of diabetic nephr opathy. At 12 weeks, diabetic animals had fivefold higher blood glucose, th reefold higher glycated hemoglobin and fivefold higher collagen glycation, compared to metabolically healthy controls; pentosidine and CML in skin col lagen were increased by approximately 30 and 150%, respectively. Administra tion of aminoguanidine, 50 mg/kg by daily intraperitoneal injection, signif icantly inhibited the development of albuminuria (approximate to 60%, P < 0 .01) in diabetic rats, without an effect on blood glucose or glycation of h emoglobin or collagen. Surprisingly, aminoguanidine failed to inhibit the i ncrease in pentosidine and CML in diabetic rat skin collagen. Similar resul ts were obtained in an independent experiment in which aminoguanidine was a dministered in drinking water at a dose of 0.5 g/l, We conclude that the th erapeutic benefits of aminoguanidine on albuminuria may not be the result o f inhibition of AGE formation. (C) 1999 Elsevier Science Ireland Ltd. All r ights reserved.