Development of reconstructed human skin containing glycated dermal equivalent to toxicity and efficacy tests of anti-glycation compounds

Author(s)

Paula Comune Pennacchi

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2016-02-03

Examining board members

Silvya Stuchi Maria Engler; Ediléia Bagatin; Luciana Biagini Lopes; Vanessa de Moura Sá Rocha

• Advisor: Silvya Stuchi Maria Engler

Abstract

The Advanced Glycation End Products (AGEs) of proteins is a common factor to the pathophysiology of a number of disorders related to aging and diseases such as diabetes mellitus (DM). The generation of the AGEs products on skin occurs mainly through non-enzymatic glycation reactions of the dermal extracellular matrix and has been touted as one of the factors responsible for loss of elasticity and disability of skin healing. The skin permeation of compounds is an important limitation for therapeutic/cosmetic efficacy of anti-AGE compounds, which must reach the deepest layers of the skin. Reconstructed skin model containing dermal equivalent modified by in vitro glycation is able to mimic the elderly human skin and represent an efficient model for the study of cells interactions and changes in extracellular matrix induced by aging and diabetes. The 3D reconstructed skin model has metabolic characteristics, permeability and activity similar to the original skin, reinforcing its role in drug permeability of investigations toxicity, irritation, safety and efficacy evaluation of compounds and differentiation of keratinocytes. A number of natural or synthetic AGEs inhibitor compounds have been recently discovered and displayed and can represent therapeutic innovation for the treatment of changes caused by the aging of the skin. In this study we performed the development of reconstructed glycated skin model and evaluated the efficacy and toxicity of anti-glycation compounds such as aminoguanidine and carnosine. In perspective, this study has contributed to the development of a new technology in vitro, and for the understanding cell-extracellular matrix interaction during the aging of skin. (AU)

• FAPESP's process: 11/22812-1 - DEVELOPMENT OF ARTIFICIAL SKIN CONTAINING GLYCATED DERMAL EQUIVALENT MIMICKING THE PATHOPHYSIOLOGY OF SKIN AGING AND DIABETES
• Grantee: Paula Comune Pennacchi
• Support Opportunities: Scholarships in Brazil - Doctorate