Aminoguanidine treatment reduces the increase in collagen stability of rats with experimental diabetes mellitus.
Alterations in the biophysical properties of connective tissues in diabetes mellitus have been attributed to the nonenzymatic glycation of the collagens and the subsequent formation of browning products, cross-linking the proteins. Aminoguanidine may bind to carbonyl groups of these nonenzymatic glycation products and thereby block the process. Rats with streptozotocin-induced diabetes were treated with aminoguanidine, 25 mg.kg-1.day-1, for 120 days. The aminoguanidine treatment did not counteract the increase in blood glucose concentrations, nor did it prevent the arrest in weight gain of diabetic rats. The increased stability in 7 mol/l urea and increased tensile strength of tail tendons from the diabetic rats, however, were prevented by the aminoguanidine treatment. Aminoguanidine did not reduce the formation of early nonenzymatic glycation products (aldimine and Amadori rearrangement products), whereas the amount of browning products (fluorescent compounds) was reduced in the tail tendon collagen of the diabetic rats. Aminoguanidine treatment of intact rats did not influence these parameters. These findings indicate that the biophysical alterations of collagens induced by experimental diabetes are caused by cross-links derived from the nonenzymatic glycation, and furthermore, that aminoguanidine treatment may prevent the concomitant changes in biophysical properties of connective tissues.
Oxlund
H
H
Department of Connective Tissue Biology, University of Aarhus, Denmark.
Andreassen
T T
TT
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003094:Collagen / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D002149:Energy Intake; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013314:Stress, Mechanical; D013710:Tendons / Q000187:drug effects / Q000378:metabolism*
D001786:Blood Glucose; D006146:Guanidines; D003094:Collagen; C004479:pimagedine