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 collagen cross-linking, glycation, and glycoxidation in Fischer 344 rats by administering the drug in their drinking water at 1 g/l from the time they were 6 months until they were 24 months of age. Body weight and food and water consumption were consistently recorded throughout the study. Plasma glucose was measured by the glucose oxidase method, and collagen cross-linking was assessed by tail tendon break time (TBT) in urea. Glycation (furosine) and 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 months 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 significantly (p <.0001) with age. However, except for a modest decrease of TBT at all ages that approached significance (p =.077), AG had no effect on collagen glycation or glycoxidation. These results are important because they suggest that alpha,beta-dicarbonyl compounds that can be trapped by aminoguanidine do not play a major role in collagen aging in the rat. Instead, post-Amadori pathways involving oxidative or nonoxidative fragmentation of the Amadori product emerge as the more likely mechanism of collagen cross-linking in aging.
Sell
D R
DR
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA. drs7@po.cwru.edu
Nelson
J F
JF
Monnier
V M
VM
D000375:Aging / Q000378:metabolism*; D000818:Animals; D003094:Collagen / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344
D017127:Glycation End Products, Advanced; D006146:Guanidines; D003094:Collagen; C004479:pimagedine