Development of glycated artificial skin and evaluation of effectiveness and toxicity of anti-glycation compounds

Abstract

Although occurring naturally during the process of aging, non-enzymatic glycation of proteins also plays a major role in cardiovascular pathologies, Alzheimer's disease and Diabetes Mellitus. These reactions altogether results in the formation of AGEs (Advanced Glycation End Products). The glycation of collagen, a structural dermis protein, may harm skin cells, especially fibroblasts, hampering their proliferative and ECM secretive capabilities, and lastly, causing death via apoptosis. In order to study the morphological and physiological changes that take place in dermis, mainly regarding the fibroblasts, predominant cells of this region, we proposed in this project a tridimensional model in which type 1 collagen pre-glycated with sodium glyoxalate will be used to mimic the diabetic dermis. Through this model it will be possible to observe the interactions between the cell and the ECM, as well as the activity of AGE-formation inhibiting compounds. This study is aimed at evaluating, through the use of immunohistochemistry techniques, confocal and second harmonic generation microscopy and zymography essays, the morphological and functional changes in artificial human skin modified by glycation, also analyzing the effectiveness of aminoguanidine and carnosine, glycation inhibitors already described in the related literature. The present study will provide important data to understand the relationship fibroblast-ECM in the context of aging and Diabetes Mellitus, and for the study of these effects in glycated artificial skin. (AU)