Choline and Cystine Deficient Diets in Animal Models with Hepatocellular Injury: Evaluation of Oxidative Stress and Expression of RAGE, TNF-α, and IL-1β

Figure 4

Diets deficient in choline (CD) or choline and cystine (CCD) decrease the formation of hepatic VLDL and antioxidants derived from thiols (for instance, glutathione), leading to hepatic steatosis (HS) and increased susceptibility to oxidative stress (OS). HS leads to OS and lipid peroxidation (LP) (directly); additionally, OS also stimulates the production of inflammatory cytokines. LP leads to the formation of reactive intermediates (glyoxal and methylglyoxal) which by interacting with proteins (amino acids) cause liver tissue modifications: carbonylation of proteins including enzymatic antioxidants (SOD, CAT, and SH) and formation of AGEs. AGEs can interact with cell receptors, RAGE, triggering a cascade reaction that increases inflammation and intracellular OS. Additionally, inflammatory cytokines increased directly by OS also contribute to the reaction described above, resulting in hepatocellular injury, hepatocyte ballooning with or without fibrosis, leading to NASH and eventually to hepatocellular carcinoma (HC).