Figure 4.

Potential mechanisms of HDS-induced liver injury. Most HDS hepatotoxicity develops through direct hepatocyte toxicity or by triggering an immune response. Toxic ingredients or their reactive metabolites cause direct hepatocyte toxicity through various mechanisms, such as oxidative stress, endoplasmic reticulum (ER) stress, DNA damage, toxic bile acids accumulation, and mitochondrial dysfunction, consequently leading to cell apoptosis or necrosis. Another important mechanism resulting in cell damage occurs when either toxic HDS ingredients, reactive metabolites, or danger damage-associated molecular patterns (DAMPs) released by stressed hepatocytes trigger an immune response. The exact mechanism leading to HDS-hepatotoxicity is still under investigation and other pathways may be involved.