IMMUNOCYTOCHEMICAL DETECTION OF ADVANCED GLYCATED END-PRODUCTS IN RATRENAL TISSUE AS A FUNCTION OF AGE AND DIABETES

Background. High blood glucose levels play major roles in the pathogen esis of renal diabetic complications through non-enzymatic glycation. For long-lived molecules this leads to formation of advanced glycation end products (AGE), and the renal extracellular matrix appears to be one of the targets for such processes. Using immunocytochemistry, we s tudied the appearance and deposition of AGE products in renal tissues from normal and diabetic rats at different ages, to evaluate the effec ts of aging and hyperglycemia. Methods. The streptozotocin-injected ra t represented our model of hyperglycaemic condition. The immunogold te chniques were applied at the light and electron microscope levels usin g specific monoclonal and polyclonal antibodies against AGE adducts. T he results were analyzed by morphometry. Results. In normoglycemic ani mals, significant increases in labeling were detected in tubular basem ent membranes and mesangial matrix at 12 to 15 months of age. In contr ast, in diabetic animals, significant increases in labeling were found for all extracellular matrices as soon as after two months of hypergl ycemia. Labelings were also detected in cellular compartments, particu larly in nuclei that showed increases in diabetic condition. The label ing was particularly intense in proximal convoluted tubules and their endosomal compartment, due to the reabsorption of urinary AGE products . Conclusion. The presence of AGE products in the renal extracellular matrix of old normoglycemic animals and their rapid appearance in hype rglycemia, indicate that AGE products may participate in the pathogene sis of renal complications. Furthermore, the non-enzymatic glycation i s not restricted to extracellular matrices but also affects cellular p roteins.