Fig. 5. Synergistic interactions between doxorubicin and lipid-loading in hepatocytes. In naïve hepatocytes (left panel), exposure to either doxorubicin or free fatty acids (FFA) results in steatosis and oxidative stress. GPX/MT-mediated adaptation acts to reduce ROS levels, minimising the necessity for cell death through apoptosis. In steatotic hepatocytes (right panel), the combination of doxorubicin and FFA exposure leads to additive lipid accumulation, and synergistic intracellular ROS levels. This overwhelms the GPX/MT adaptive system, resulting in increased cell death, release of pro-inflammatory signals and potentiation through the fatty liver disease spectrum.