Abstract: Advanced glycation end products (AGEs) are generated spontaneously in cells; however, under conditions of hyperglycemia and lipid peroxidation, their levels are higher than usual, which contribute to the development of diseases such as the nonalcoholic fatty liver disease (NAFLD). NAFLD is associated with oxidative stress (OS), which is linked to the transition of steatosis to steatohepatitis due to lipid peroxidation. The AGE-receptor interaction in hepatic stellate cells leads to an increase in reactive oxygen species and enhances the proliferation and activation of these cells, worsening liver fibrosis and disease progression. In this vicious cycle, there is production of (carboxymethyl)lysine, a biomarker for products of advanced glycation and lipid peroxidation, being a shared component between the two pathways. In this review, we aim to compile evidence to support the basic molecular mechanisms of AGEs and OS generation and their influence, independently or combined, on the evolution of NAFLD. The deeper understanding of the interrelations of AGEs + OS may help to elucidate the pathogenic pathways of NAFLD and to devise rational therapeutic interventions for this disease, with an expected positive impact on quality of life of patients.
Keywords: oxidative stress; liver; AGEs; nonalcoholic fatty liver disease; molecular mechanism of biological activity
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Santos, J.C.F.; Valentim, I.B.; de Araújo, O.R.P.; Ataide, T.R.; Goulart, M.O.F. Development of Nonalcoholic Hepatopathy: Contributions of Oxidative Stress and Advanced Glycation End Products. Int. J. Mol. Sci. 2013, 14, 19846-19866.
Santos JCF, Valentim IB, de Araújo ORP, Ataide TR, Goulart MOF. Development of Nonalcoholic Hepatopathy: Contributions of Oxidative Stress and Advanced Glycation End Products. International Journal of Molecular Sciences. 2013; 14(10):19846-19866.
Santos, Juliana C.F.; Valentim, Iara B.; de Araújo, Orlando R.P.; Ataide, Terezinha R.; Goulart, Marília O.F. 2013. "Development of Nonalcoholic Hepatopathy: Contributions of Oxidative Stress and Advanced Glycation End Products." Int. J. Mol. Sci. 14, no. 10: 19846-19866.