COMPARISON OF THE EFFECT OF DIFFERENT INHIBITORS ON THE NONENZYMATIC GLYCATION OF RAT TAIL TENDONS AND BOVINE SERUM-ALBUMIN

The biomechanical and biochemical properties of collagen are changed b y non-enzymatic glycation culminating in increased cross-linking. We h ave previously shown that dibasic amino acids such as L-arginine inhib it in vitro the non-enzymatic glycation of soluble proteins and insolu ble connective tissue macromolecules. In the present in vitro study we obtained evidence that the nucleophilic hydrazine derivative aminogua nidine and the non-steroidal antirheumatic drug ibuprofen inhibit the formation of fluorescent advanced glycation end products (AGEs) to a c omparable extent, while arginine is ineffective as a consequence of it s tendency to form AGEs itself. Periodic replacement of glycated argin ine in the rat tail tendon system, however, engendered an inhibition o f fluorescence similar to that obtained by the other inhibitors. Long- term glycation of rat tail tendons caused a significant increase in Yo ung's modulus, which could also be inhibited by periodically renewed a rginine. In contrast to ibuprofen, aminoguanidine and arginine-lysine inhibited the marked increase in maximum contraction force of long-ter m glycated rat tail tendons. As opposed to other inhibitors, aminoguan idine also reduced the thermal contraction force of native tendons, sh ifted the maximum contraction temperature to markedly lower values and solubilized a significant part of the rat tail tendon collagen. These findings indicate that the in vitro alterations of rat tail tendon co llagen induced by nonenzymatic glycation can be prevented by arginine, arginine-lysine and aminoguanidine. However, collagen structure is se riously affected by aminoguanidine.