Implication of advanced glycation endproducts (AGEs) related to their receptor RAGE and glyoxalase-I (Glo-I) in chronic liver disease and hepatocellular carcinoma (HCC)

Marcus Hollenbach


The glyoxalase system is formed by the enzymes glyoxalase-I (Glo-I) and glyoxalase-II (Glo-II) and is responsible for the detoxification of methylglyoxal (MGO). MGO is a by-product in glycolysis, threonine-catabolism and ketone bodies pathway leading to formation of advanced glycation endproducts (AGEs) and oxidative stress. AGEs bind to their receptor RAGE and activate pro-inflammatory transcription factors such as NF-κB by means of ERK1/2, PI3K, JNK and others. This review focuses on implication of Glo-I/AGE/RAGE system in chronic liver disease and HCC. Recent work showed importance of AGEs and RAGE in the latter. Both have been upregulated in fibrosis and silencing of RAGE reduced fibrosis and tumor growth of HCC. In contrast, Glo-I was demonstrated to be involved in development and progression of cirrhosis and new data offer Glo-I as an innovative target for antifibrotic therapy.

In a conclusion, there is growing evidence regarding involvement of Glo-I/AGE/RAGE system in chronic liver diseases with an interesting new therapeutic opportunity. These findings need further elucidation in preclinical and clinical studies.


ethyl pyruvate, cirrhosis, fibrosis, methylglyoxal, AGEs, CCl4

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