Marcus Hollenbach

By Marcus Hollenbach

Inflammation caused by oxidative stress (ROS) is a main driver for development of chronic inflammatory liver disease leading to fibrosis and cirrhosis. An important source of ROS constitutes methylglyoxal (MGO). MGO is formed as a by-product in glycolysis, threonine catabolism, and ketone bodies pathway leading to formation of advanced glycation end products (AGEs). AGEs bind to their receptor for AGEs (RAGE) and activate intracellular transcription factors, such as nuclear factor-κB (NF-κB), resulting in production of pro-inflammatory cytokines and ROS. The enzymes glyoxalase-I (Glo-I) and glyoxalase-II (Glo-II) form the glyoxalase system and are essential for the detoxification of methylglyoxal (MGO). This chapter highlights Glo-I and (R)AGE in chronic liver disease with focus on fibrosis and cirrhosis. AGEs and RAGE have been shown to be upregulated in fibrosis, and silencing of RAGE reduced the latter. In contrast, recent study highlighted reduced expression of Glo-I in cirrhosis with consecutive elevation of MGO and oxidative stress. Interestingly, modulation of Glo-I activity by ethyl pyruvate resulted in reduced activation of hepatic stellate cells and reduced fibrosis in CCl4 model of cirrhosis. In conclusion, Glo-I and R(AGE) are important components in development and progression of chronic liver disease and constitute interesting therapeutic target.

Part of the book: Liver Cirrhosis