The reaction of methylglyoxal with aminoguanidine under physiological conditions and prevention of methylglyoxal binding to plasma proteins

Increased formation of methylglyoxal in clinical diabetes mellitus and metabolism by the glyoxalase system has been linked to the development of clinical complications of diabetes: retinopathy, neuropathy and nephropathy. Aminoguanidine has been proposed as a prophylactic agent for preventive therapy of diabetic complications. Methylglyoxal reacted with aminoguanidine under physiological conditions to form two isomeric triazines, 3-amino-5-methyl-1,2,4-triazine and 3-amino-6-methyl-1,2,4-triazine. The mean second order rate constant for the reaction of methylglyoxal with aminoguanidine, k MG,AG = 0.39 ± 0.06 M −1 sec −1 at pH 7.4 and 37°. Under these conditions, no methylglyoxal bisguanylhydrazone was detected. Aminoguanidine prevented the irreversible modification of human plasma protein by a physiological concentration of methylglyoxal (1 μM); the median inhibitory concentration IC 50 value of aminoguanidine was 203 ± 16 μM (N = 28). The scavenging of methylglyoxal by aminoguanidine may contribute to the beneficial effects of aminoguanidine in the prevention of vascular pathogenesis in diabetes.