Comparison of the effect of different inhibitors of the non-enzymatic glycation of rat tail tendons and bovine serum albumin.
The biomechanical and biochemical properties of collagen are changed by non-enzymatic glycation culminating in increased cross-linking. We have previously shown that dibasic amino acids such as L-arginine inhibit in vitro the non-enzymatic glycation of soluble proteins and insoluble connective tissue macromolecules. In the present in vitro study we obtained evidence that the nucleophilic hydrazine derivative aminoguanidine and the non-steroidal anti-rheumatic drug ibuprofen inhibit the formation of fluorescent advanced glycation end products (AGEs) to a comparable extent, while arginine is ineffective as a consequence of its tendency to form AGEs itself. Periodic replacement of glycated arginine in the rat tail tendon system, however, engendered an inhibition of fluorescence similar to that obtained by the other inhibitors. Long-term glycation of rat tail tendons caused a significant increase in Young's modulus, which could also be inhibited by periodically renewed arginine. In contrast to ibuprofen, aminoguanidine and arginine-lysine inhibited the marked increase in maximum contraction force of long-term glycated rat tail tendons. As opposed to other inhibitors, aminoguanidine also reduced the thermal contraction force of native tendons, shifted 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 collagen induced by non-enzymatic glycation can be prevented by arginine, arginine-lysine and aminoguanidine. However, collagen structure is seriously affected by aminoguanidine.
Menzel
E J
EJ
Institute of Immunology, University of Vienna, Austria.
Reihsner
R
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D012995:Solubility; D013623:Tail; D013710:Tendons / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004151:Dipeptides; D004791:Enzyme Inhibitors; D006146:Guanidines; C104090:arginyllysine; D012710:Serum Albumin, Bovine; D001120:Arginine; C004479:pimagedine; D007052:Ibuprofen