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 degrees. Under these conditions, no methyglyoxal bisguanylhydrazone was detected. Aminoguanidine prevented the irreversible modification of human plasma protein by a physiological concentration of methylglyoxal (1 mu M); the median inhibitory concentration IC50 value of aminoguanidine was 203 +/- 16 mu M (N = 28). The scavenging of methylglyoxal by aminoguanidine may contribute to the beneficial effects of aminoguanidine in the prevention of vascular pathogenesis in diabetes.