ADVANCED GLYCATION ENDPRODUCTS (AGES) INDUCE OXIDANT STRESS IN THE GINGIVA - A POTENTIAL MECHANISM UNDERLYING ACCELERATED PERIODONTAL-DISEASE ASSOCIATED WITH DIABETES

We hypothesizes that one mechanism underlying advanced periodontal dis ease in diabetes may involve oxidant stress in the gingiva, induced by the effects of Advanced Glycation Endproducts (AGE5), the irreversibl e products of non-enzymatic glycation and oxidation of proteins and li pids which accumulate in diabetic plasma and tissue: Infusion of AGE a lbumin, a prototypic ligand, into mice resulted in increased generatio n of thiobarbituric acid reactive substances (TEARS) compared with inf usion of non-glycated albumin in the gingiva: as well as in the lung, kidney and brain. Pretreatment of the animals with the antioxidants pr obucol or N-acetylcysteine (NAC) prevented the generation of TEARS in the gingiva. Affinity-purified antibody to AGEs demonstrated increased immunoreactivity for AGEs in the vasculature and connective tissues o f the gingiva in streptozotocin-induced diabetic mice compared to non- diabetic controls. Increased immunoreactivity for AGEs was also demons trated in the gingiva of diabetic humans compared with non-diabetic in dividuals via immunohistochemistry and ELISA. Consistent with these,da ta, immunohistochemistry for heme oxygenase-1, a masker of enhanced ox idant stress, was increased in the gingival vasculature of diabetic mi ce and humans compared with non-diabetic controls. These data suggest that AGEs present in. diabetic gingiva may be associated with a state of enhanced oxidant stress, a potential mechanism for accelerated tiss ue injury.