Effect of chronic aminoguanidine treatment on age-related glycation, glycoxidation, and collagen cross-linking in the Fischer 344 rat

Aminoguanidine (AG) is an inhibitor of protein modification by the advanced Maillard reaction. We evaluated its effects in preventing age-related coll agen cross-linking, glycation, and glycoxidation in Fischer 344 rats by adm inistering the drug in their drinking water at 1 g/I from the time they wer e 6 months until they were 24 months of age. Body weight and food and water consumption were consistently recorded throughout the study. Plasma glucos e was measured by the glucose oxidase method, and collagen cross-linking wa s assessed by tail tendon break time (TBT) in urea. Glycation (furosine) an d glycoxidation (pentosidine and carboxymethyllysine) were assessed by high -performance liquid chromatography in acid hydrolysates of skin and tendon collagen. Water consumption dramatically increased (p < .0001) after 20 mon ths of age and was accelerated in the control versus AG-treated rats (p < . 0001). Plasma glucose increased approximately 20% at age 19 months in both groups (p < .0001). TBT, glycation, and glycoxidation all increased signifi cantly (p < .0001) with age. However, except for a modest decrease of TBT a t all ages that approached significance (p = .077), AG had no effect on col lagen glycation or glycoxidation. These results are important because they suggest that (alpha,beta -dicarbonyl compounds that can be trapped by amino guanidine do not play a major role in collagen aging in the rat. Instead, p ost-Amadori pathways involving oxidative or nonoxidative fragmentation of t he Amadori product emerge as the more likely mechanism of collagen cross-li nking in aging.